Transcranial Alternating Current Stimulation for Chronic Insomnia: A Meta-Analytic Evaluation of Sleep Restoration and Safety in Adults

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Aboelkhier, Anas Mansour, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7420412/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Feb, 2026 Read the published version in BMC Psychiatry → Version 1 posted 10 You are reading this latest preprint version Abstract Background Chronic insomnia affects approximately one-third of adults globally, imposing substantial health burdens with limited effective treatments. Transcranial alternating current stimulation (tACS) emerges as a non-invasive neuromodulatory approach, though its efficacy and safety profile require systematic evaluation. Methods We systematically searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials through July 2025 for randomized controlled trials (RCTs) evaluating tACS in adults with chronic insomnia. Primary outcomes included Pittsburgh Sleep Quality Index (PSQI) scores, sleep onset latency (SOL), total sleep time (TST), and sleep efficiency. Secondary outcomes encompassed remission/response rates, daytime disturbances, mood symptoms, and adverse events. Data were pooled using random-effects models. Risk of bias and evidence certainty were assessed via Cochrane RoB 2.0 and GRADE. Results Four RCTs (n = 247) were included. tACS significantly reduced SOL at 2 weeks (MD = − 56.90 min; 95% CI: −74.44 to − 39.36) and 4 weeks (MD = − 52.20 min; −67.03 to − 37.37), improved PSQI (MD = − 5.73; −8.35 to − 3.10; p < 0.0001), increased TST (MD = + 85.29 min; 33.42 to 137.15; p = 0.0013), and reduced daytime disturbances (MD = − 0.94; −1.13 to − 0.76; p < 0.0001). Response rates favored tACS (RR = 11.21; 3.20–39.23; p = 0.0002). Mood improvements were not sustained beyond 8 weeks. No significant adverse events emerged versus sham (RR = 1.06; 0.16–6.95). Heterogeneity ranged moderate-to-high (I² = 46.9–97.2%). Conclusion tACS demonstrates rapid efficacy (2–6 weeks) and safety for core insomnia symptoms. Sustained benefits require protocol optimization and long-term evaluation. Transcranial alternating current stimulation chronic insomnia meta-analysis sleep quality randomized controlled trial neuromodulation Pittsburgh Sleep Quality Index sleep onset latency Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Introduction Chronic insomnia is a prevalent sleep disorder that significantly affects both public health and individual well-being worldwide. It is characterized by persistent difficulty with sleep onset, maintenance, or quality despite adequate opportunity for rest, impacting a substantial proportion of adults (Bhaskar, Hemavathy, and Prasad 2016; Mai and Buysse 2008). Estimates suggest that up to 33% of adults may experience chronic insomnia (Benjafield et al. 2025 ), and approximately 12% of Americans have received a formal diagnosis (Academy of Sleep Medicine n.d.). The consequences of chronic insomnia extend beyond nighttime disturbances, contributing to increased risks of depression, anxiety, substance use disorders, motor vehicle accidents, and neurodegenerative conditions such as Alzheimer’s disease (Academy of Sleep Medicine n.d.; Mai and Buysse 2008). Its negative impact on health-related quality of life is comparable to that of other chronic medical conditions (Mai and Buysse 2009 ). Individuals with more severe insomnia are at greater risk of persistent sleep difficulties over time (Morin et al. 2020). Current treatment options have notable limitations. Pharmacological therapies can cause adverse effects, and adherence to cognitive behavioral therapy for insomnia (CBT-I) is often inconsistent. This has created growing interest in alternative and complementary treatments. Transcranial alternating current stimulation (tACS), a non-invasive brain stimulation technique, has emerged as a promising intervention for modulating brain oscillations and potentially restoring healthy sleep patterns (Lee et al. 2025; Motamedi et al. 2023 ). The core principle of tACS is the entrainment of endogenous brain rhythms, whereby externally applied alternating currents synchronize with and influence intrinsic neural oscillations (Tavakoli and Yun 2017; Wischnewski, Alekseichuk, and Opitz 2023). By adjusting the frequency, amplitude, and phase of the current, tACS can selectively target brain regions and modulate neuronal networks involved in sleep regulation (Agboada, Zhao, and Wischnewski 2025). For example, stimulation in the delta frequency range can induce and sustain slow-wave activity, which is essential for deep sleep (Ketz et al. 2018 ; Takahashi et al. 2024 ). This modulation of brain rhythms may promote neuroplastic changes and enhance cognitive processes such as sleep-dependent long-term memory consolidation (Ketz et al. 2018 ; Lustenberger et al. 2016 ). In the context of insomnia, tACS has the potential to restore disrupted brain oscillations. Chronic insomnia is often associated with dysregulation of the sleep–wake system, including alterations in brainwave patterns during both sleep and wakefulness. Applying tACS at specific frequencies may re-establish healthy oscillatory patterns, thereby improving sleep onset, continuity, and architecture. Some studies have reported enhancements in sleep architecture, including increased NREM stage 2 sleep (Dondé et al. 2021 ), although the precise mechanisms remain incompletely understood. The growing body of research on tACS for insomnia, coupled with the shortcomings of current treatments, underscores the need for a comprehensive meta-analysis. While individual studies have demonstrated promising effects of tACS, such as increased total sleep time, reduced sleep onset latency, and improved sleep efficiency (Shao et al. 2024 ; Takeuchi et al. 2025 ), findings remain heterogeneous. Personalized stimulation frequencies appear more effective than fixed-frequency protocols in improving sleep quantity and facilitating sleep onset (Ayanampudi et al. 2023 ). Furthermore, tACS has been shown to reduce cortical arousal by decreasing high-frequency EEG power, suggesting a direct influence on wakefulness-related neural activity (Shi et al. 2025 ). Improvements in sleep quality, efficiency, and insomnia severity have been particularly notable in older adults (Zhu et al. 2024 ). Importantly, tACS has been associated with minimal adverse effects and may offer lasting therapeutic benefits (Q. Zhou et al. 2021 ). This meta-analysis aims to systematically evaluate current evidence on tACS for chronic insomnia, assessing both subjective outcomes, such as the Pittsburgh Sleep Quality Index (PSQI), and objective metrics, including sleep onset latency (SOL), total sleep time (TST), and sleep efficiency. Adverse event rates and durability of benefits will also be examined to provide a thorough understanding of its safety and long-term efficacy. The results are intended to inform clinical decision-making, guide future research, and support the development of improved treatment strategies for adults with chronic insomnia. Methods 3.1 Search Strategy and Data Sources We conducted a systematic search of four electronic databases: PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials up to July 2025 to evaluate the efficacy and safety of transcranial alternating current stimulation (tACS) in adults with chronic insomnia. The search strategy incorporated the following terms and their relevant synonyms or MeSH terms: ("transcranial alternating current stimulation" OR tACS) AND ("chronic insomnia" OR "persistent insomnia" OR "long-term insomnia"). Two independent reviewers screened study titles and abstracts using Rayyan to manage records, maintain blinding, and track conflicts (Ouzzani et al. 2016 ). Discrepancies were resolved by a third reviewer. Full texts of potentially eligible studies were retrieved for final inclusion. This systematic review was conducted by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Page et al. 2021 ). The review protocol was registered with PROSPERO, the international prospective register of systematic reviews (CRD420251121367). 3.2 Selection Criteria We included studies that: (1) were randomized controlled trials (RCTs), non-randomized controlled trials, or crossover trials; (2) enrolled adults aged 18 years or older with a diagnosis of chronic insomnia; (3) evaluated transcranial alternating current stimulation (tACS) as the primary intervention; (4) reported at least one sleep-related outcome; and (5) were published in English. Studies were excluded if they: (1) involved pediatric populations; (2) addressed acute or short-term insomnia; (3) combined tACS with other neurostimulation techniques without isolating the effect of tACS; (4) were case reports, editorials, protocols, or reviews; or (5) were animal or in vitro studies. 3.3 Outcomes of interest included The primary outcomes assessed in this review included Pittsburgh Sleep Quality Index (PSQI) total score reduction, response rate (defined as ≥ 50% reduction in PSQI score), sleep onset latency (SOL), total sleep time (TST), and sleep efficiency (%). Secondary outcomes included remission rate (defined as PSQI < 5), sleep quality (specific PSQI components), daytime disturbances (PSQI components), adverse event (AE) rate, long-term durability of treatment effect (≥ 8 weeks), and changes in depression and anxiety scores measured by standardized scales, including the Hamilton Depression Rating Scale (HDRS or HAMD) and the Hamilton Anxiety Rating Scale (HARS or HAMA). 3.4 Quality Assessment and Data Extraction Relevant data from the included studies were extracted into a predefined online data extraction sheet. The extracted information included: (1) study characteristics; (2) baseline characteristics of the study population; (3) risk of bias domains; and (4) primary and secondary outcome measures. The risk of bias and methodological quality of the included studies were independently assessed by four reviewers using the Cochrane Risk of Bias 2.0 (RoB 2) tool for randomized controlled trials (Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ 2024; Sterne et al. 2019 ). This tool evaluates five key domains: (1) the randomization process (selection bias); (2) deviations from intended interventions (performance bias); (3) outcome measurement (detection bias); (4) missing outcome data (attrition bias); and (5) selection of the reported results (reporting bias), while also considering other potential sources of bias. 3.4 Data Synthesis and Statistical Analysis Meta-analyses were conducted using R software (version 4.5.1) with the meta package (version 1.17). A random-effects model (DerSimonian–Laird method) was applied (DerSimonian and Laird 2015), and results were reported as mean differences (MDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, each with 95% confidence intervals (CIs). Continuous data (sample size, mean, and standard deviation) were analyzed using the metacont() function, and dichotomous data (events and total participants) were analyzed using the metabin() function. Subgroup analyses were performed based on follow-up duration, grouping studies into 2-week, 4-week, 6-week, and 8-week time points to evaluate the effect of the intervention over time. Statistical heterogeneity was assessed using the I² statistic, τ², and Cochran’s Q test, while subgroup differences were evaluated using χ² tests. No sensitivity analyses or meta-regression were performed due to the small number of included studies, as these methods would have been ineffective and unlikely to alter the main findings. 3.5 Certainty of Evidence Assessment We assessed the certainty of evidence for each outcome using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach (Schünemann et al. 2008 ). The following domains were evaluated: risk of bias, inconsistency, imprecision, publication bias, and other considerations. For each outcome, the domains were summarized in an evidence profile table, which included the number of contributing studies, domain-specific ratings, and the final certainty rating. Results 4.1 Study Selection and Characteristics The systematic literature search identified 25 records from electronic databases (PubMed: n = 7; Web of Science: n = 10; Cochrane Library: n = 8; Scopus: n = 0). After the removal of 14 duplicate records, 11 unique records underwent title and abstract screening. Seven records were excluded at this stage. The full texts of the remaining four records were successfully retrieved and assessed for eligibility. No studies were excluded during the full-text assessment phase, as all met the predefined inclusion criteria. Consequently, four randomized controlled trials (RCTs) were included in the final systematic review as shown in Fig. 1 . The characteristics of the included studies are summarized in Tables 1 . All studies were parallel-group RCTs, except for Motamedi 2022, which employed a randomized single-crossover design. Sample sizes ranged from 9 to 120 participants (Total N = 247). Three studies were conducted in China, while one was conducted in the USA. Study durations varied between 2 weeks and 8 weeks. Table 1 Summary of included studies Study ID Location Study Design Total Participants Intervention Dose Study Duration Follow up Duration Outcomes Key findings Wang 2025 China RCT 56 tACS 2 mA/ 10 HZ 2 weeks 4–6 weeks PSQI, HAMD-17, HAMA Superior sustained improvements in sleep quality, depression, anxiety, cognition Zhu 2024 China RCT 120 tACS 15 mA/77.5 Hz 4 weeks 8 weeks PSQI, SOL. TST, HAMD Age may influence treatment response Motamedi 2022 USA randomized single-crossover trial 9 tACS 0.75 mA / .0.75 Hz 2 weeks 6 weeks WASO, Sleep onset latency, QoL Non-significant reduction in sleep onset latency and WASO Wang 2019 China RCT 62 tACS 15 mA/ 77.5 Hz 8 weeks 4 weeks Response rate Week 8 response rate: 53.4% (16/30) vs 16.7% (5/30) (p = 0.009) RCT: Randomized Controlled Trial, tACS: Transcranial Alternating Current Stimulation, PSQI: Pittsburgh Sleep Quality Index, HAMD-17: Hamilton Depression Rating Scale-17, HAMA: Hamilton Anxiety Rating Scale, SOL: Sleep Onset Latency, TST: Total Sleep Time, WASO: Wake After Sleep Onset QoL: Quality of Life Participants were adults with insomnia, diagnosed primarily using DSM-5 or ICSD-3 criteria. The mean age of participants across studies ranged from 48.6 to 55.3 years, with a higher proportion of females. Baseline insomnia duration showed considerable heterogeneity, ranging from a mean of 4.39 years to 58.1 years. All studies evaluated transcranial alternating current stimulation (tACS) as the active intervention compared to a sham control. Primary outcomes focused on sleep parameters, measured using the Pittsburgh Sleep Quality Index (PSQI), sleep onset latency (SOL), total sleep time (TST), wake after sleep onset (WASO), and sleep quality sub-scores. Secondary outcomes included depressive symptoms (Hamilton Depression Rating Scale, HAMD-17), anxiety symptoms (Hamilton Anxiety Rating Scale, HAMA), response rates, and quality of life (QoL) where assessed and illustrated in Table 3 . Key baseline characteristics (age, sex distribution, diagnostic scores, insomnia duration) were generally well-balanced between intervention and sham groups within each study and shown in Table 2 . Table 2 Baseline of the Characteristics of the included studies Study ID Group Sample size Age mean (SD) Males (%) Diagnostic criteria (DSM-5, ICSD-3) Insomnia duration Wang 2025 tACS group 28 50.2 (11) 5 (17.9%) 14.4 (2.4) 7 (4.44) sham 28 48.6 (14.7) 8 (28.6%) 14.7 (2.1) 7 (4.44) Zhu 2024 tACS group 60 48.93 (12.78) 19 (31.667%) 13.85 (1.75) 4.48 (5.70) sham 60 52.25 (10.38) 23 (38.333%) 13.77 (2.0) 4.39 (5.43) Motamedi 2022 tACS group 9 50.2 (10) 1 (11%) NA 7.8 (3.4) sham 9 50.2 (10) 1 (11%) NA 7.8 (3.4) Wang 2019 tACS group 31 55.3 (8) 8 (25.8%) 13.26 (2.08) 51.6 (46.3) sham 31 52.5 (10.7) 7 (22.6%) 13.13 (1.59) 58.1 (80.9) DSM-5: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, ICSD-3: International Classification of Sleep Disorders, 3rd Edition Table 3 Outcomes of included studies Study ID Timepoint Total PSQI (post) PSQI Total > = 8W SOL (min) (post) TST (min) (post) Sleep quality Sub score (post) Daytime Disturbances (post) HAMD (post) HAMA (post) tACS Sham tACS Sham tACS Sham tACS Sham tACS Sham tACS Sham tACS Sham tACS Sham Wang 2025 2 weeks 5.4 (3.6) 13.7 (3.2) NA NA 23.8 (16.7) 80.7 (44.3) 480 (54) 288 (42) 0.7 (0.7) 2.2 (0.6) 0.4 (0.7) 1.4 (1) 3 (2.7) 9.2 (2.8) 4 (3.4) 10 (3.8) 4 weeks 6.1 (4) 13.6 (3.1) NA NA 27.5 (16.9) 83.2 (47.4) 390 (60) 294 (36) 0.9 (0.7) 2 (0.5) 0.4 (0.6) 1.4 (1) 3.1 (2.7) 9.4 (2.9) 4.3 (3.4) 10.2 (4) 6 weeks 6.3 (3.8) 13.6 (3.4) NA NA 29.3 (20.5) 81.8 (47.7) 390 (66) 288 (36) 0.9 (0.7) 2.1 (0.6) 0.3 (0.5) 1.4 (1) 38 (3.3) 9.4 (2.9) 4.8 (4.2) 10.4 (4.2) Zhu 2024 Baseline 13.85(1.7) 13.77 (2) 13.85 (1.7) 13.77 (2) 93.25 (60.68) 79.67(53.5) 208.8 (66) 240.6 (66) 5.23 (0.79) 5.2 (0.88) 3.37 (1.31) 3.5 (1.13) 7.13 (3.6) 6.57 (3.33) 7.25 (6.84) 6.63 (5.92) 4 weeks 6.12 (3.2) 8.58 (3.22) NA NA 42.18 (37.69) 48.67 (41.8) 361.2 (85.2) 325.8 (70.2) 2.67 (1.54) 3.18 (1.55) 1.3 (.083) 2.23 (1.43) 3.22 (2.19) 2.45 (2.32) 3.58 (4.14) 3.22 (4.29) 8 weeks NA NA 6.4 (3.9) 9.4 (3.3) 41.27 (38) 50.33 (49.12) 350.4 (81 317.4 (80.4) 2.45 (1.78) 3.55 (1.53) 1.52 (1.08) 2.53 (1.26) 2.42 (2.69) 2.6 (2.76) 2.42 (2.69) 3.07 (3.34) Motamedi 2022 Baseline 14.4 (2.9) NA NA NA 62 (40) NA 336 (48) NA NA NA NA NA NA NA 13.8 (9) NA 6 weeks 8.2 (4.3) NA NA NA 37 (31) 39.9 (56.3) 378 (72) NA NA NA NA NA NA NA 10.3 (8.5) NA Wang 2019 4 weeks intervention 5.93 (3.9) 8.43 (3.9) NA NA 31.2 (21.53) 66.17 (50.23) 360.6 (96.41) 313.8 (75.52) 2.37 (1.77) 3.4 (1.85) 1.13 (0.82) 1.37 (1.61) NA NA NA NA 4 weeks follow-up 6.73 (4.5) 9.93 (4.04) NA NA 38.5 (20.9) 84.67 (65.14) 343.2 (88.4) 294 (96.4) 5.13 (0.8) 4.93 (1.02) 2.63 (1.1) 3 (1.12) NA NA NA NA 4.2 Risk of Bias of Included Studies The risk of bias was assessed using the Cochrane RoB 2 tool across five domains. Two studies were judged to have a low overall risk of bias, supported by adequate randomization, allocation concealment, double-blinding, complete outcome data, appropriate outcome measurement methods, and adherence to pre-specified analysis plans (H. X. Wang et al. 2019 ; Zhu et al. 2024 ). Two studies were rated as having some concerns (Motamedi et al. 2023 ; L. Wang et al. 2025). In Wang et al. (2025), this was due to limited reporting on allocation concealment. In Motamedi et al. (2022), concerns arose from unclear randomization procedures, incomplete blinding of assessors, deviations from pre-specified analysis plans, and a small sample size. Overall, the methodological quality was acceptable, with most studies demonstrating low risk in key domains such as outcome measurement, handling of missing data, and adherence to intended interventions. A visual summary of the risk of bias assessments is provided in Fig. 2 . 4.3 Primary Outcomes 4.3.1 Sleep Onset Latency (SOL) Six studies reported a sleep quality subscore (n = 234; 138 in the tACS group and 243 in the sham group). Compared with the control, the intervention was associated with a significant improvement in sleep quality (MD = − 1.13, 95% CI: −1.38 to − 0.88, p < 0.0001), with moderate heterogeneity across studies (I² = 46.9%, p = 0.0935). The effect of the intervention was further examined at four follow-up time points: 2, 4, 6, and 8 weeks. At 2 weeks, a significant reduction in sleep onset latency (SOL) was observed (MD = − 56.90, 95% CI: −74.44 to − 39.36), favoring the intervention group. At 4 weeks, three studies were included, yielding a pooled mean difference of − 52.20 (95% CI: −67.03 to − 37.37), significantly favoring the intervention, with no observed heterogeneity (I² = 0%, p = 0.5438). At 6 weeks, the pooled mean difference was − 31.36 (95% CI: −79.43 to 16.72), with substantial heterogeneity (I² = 77.4%, p = 0.0353). The 95% CI crossed the null, indicating no statistically significant effect. At 8 weeks, the effect size was smaller (MD = − 9.06, 95% CI: −24.79 to 6.67), with no statistically significant difference between groups, as shown in Fig. 3 4.3.2 PSQI Total Score Reduction The PSQI was reported in five studies (n = 348; 174 in the tACS group and 174 in the sham group). Compared with the control, tACS produced a significant improvement in PSQI scores (MD = − 5.73, 95% CI: −8.35 to − 3.10, p < 0.0001), with considerable heterogeneity (I² = 91.5%, p < 0.0001). The effect of the intervention was further evaluated at follow-up durations of 2, 4, and 6 weeks. At 2 weeks, a significant reduction in PSQI scores was observed (MD = − 8.30, 95% CI: −10.08 to − 6.52), favoring the intervention group. At 4 weeks, three studies were included, yielding a pooled mean difference of − 4.35 (95% CI: −7.49 to − 1.21), also favoring the intervention, though with considerable heterogeneity (I² = 90.2%, p < 0.0001). At 6 weeks, one study (Wang 2025) reported a significant reduction (MD = − 7.30, 95% CI: −9.19 to − 5.41), with high heterogeneity (I² = 91.5%). The test for subgroup differences between time points was not statistically significant (χ² = 4.59, df = 2, p = 0.1006), suggesting that the effect of tACS on PSQI scores was relatively consistent across follow-up durations despite varying heterogeneity, as shown in Fig. 4 4.3.3 Total Sleep Time (TST) Total sleep time (TST) was reported in six study arms (n = 468; 234 in the tACS group and 234 in the sham group). Compared with the control group, the intervention produced a significant increase in TST (MD = 85.29 minutes, 95% CI: 33.42 to 137.15, p = 0.0013), although substantial heterogeneity was present (I² = 94.8%, p < 0.0001). The effect of the intervention was further examined at follow-up durations of 2, 4, 6, and 8 weeks. At 2 weeks, the intervention group demonstrated a significant increase in TST compared with the control group (MD = 192.00 minutes, 95% CI: 166.66 to 217.34). At 4 weeks, three studies were included, yielding a pooled mean difference of 61.35 minutes (95% CI: 19.22 to 103.49), favoring the intervention, though with substantial heterogeneity (I² = 80.5%, p = 0.0060). At 6 weeks, Wang (2025) reported a significant increase in TST (MD = 102.00 minutes, 95% CI: 74.15 to 129.85). At 8 weeks, Zhu (2024) reported an increase of 33.00 minutes (95% CI: 4.12 to 61.88), as shown in Fig. 5 . 4.4 Secondary Outcomes 4.4.1 Daytime Disturbances Six study arms reported daytime disturbances (n = 468; 234 in the tACS group and 234 in the sham group). Compared with the control group, the intervention significantly reduced daytime disturbances (MD = − 0.94, 95% CI: −1.13 to − 0.76, p < 0.0001), with low heterogeneity across studies (I² = 6.0%, p = 0.378). The effect of the intervention was further assessed at follow-up durations of 2, 4, 6, and 8 weeks. At 2 weeks, Wang (2025) reported a significant reduction in daytime disturbances in the intervention group compared with the control group (MD = − 1.00, 95% CI: −1.45 to − 0.55). At 4 weeks, three studies were included, yielding a pooled mean difference of − 0.79 (95% CI: −1.19 to − 0.39), favoring the intervention, with moderate heterogeneity (I² = 50.1%, p = 0.135). At 6 weeks, Wang (2025) reported a significant reduction (MD = − 1.10, 95% CI: −1.51 to − 0.69). At 8 weeks, Zhu (2024) found lower daytime disturbance scores in the intervention group compared with the control group (MD = − 1.01, 95% CI: −1.43 to − 0.59), as shown in Fig. 6 . 4.4.2 Sleep Quality Subscore The sleep quality subscore was reported in six study arms (n = 468; 234 in the tACS group and 234 in the sham group). Compared with the control group, the intervention resulted in a significant improvement in sleep quality (MD = − 1.13, 95% CI: −1.38 to − 0.88, p < 0.0001), with moderate heterogeneity across studies (I² = 46.9%, p = 0.0935). The effect of the intervention was further examined at follow-up time points of 2, 4, 6, and 8 weeks. At 2 weeks, Wang (2025) reported a marked improvement in the intervention group compared with the control group (MD = − 1.50, 95% CI: −1.84 to − 1.16). At 4 weeks, three studies were included, yielding a pooled mean difference of − 0.90 (95% CI: −1.30 to − 0.51), favoring the intervention, with moderate heterogeneity (I² = 39.6%, p = 0.1912). At 6 weeks, Wang (2025) also reported a significant improvement (MD = − 1.20, 95% CI: −1.54 to − 0.86). At 8 weeks, Zhu (2024) found sustained benefits, with the intervention group continuing to show lower scores (MD = − 1.10, 95% CI: −1.69 to − 0.51), as shown in Fig. 7 . 4.4.3 Depression Scores Depression scores were reported in four study arms (n = 408; 204 in the tACS group and 204 in the sham group). Compared with the control group, the intervention resulted in a significant reduction in depression scores (MD = − 3.46, 95% CI: −6.61 to − 0.30, p = 0.0319), with considerable heterogeneity across studies (I² = 97.2%, p < 0.0001). The effect of the intervention was further examined at follow-up durations of 2, 4, 6, and 8 weeks. At 2 weeks, Wang (2025) reported a notable reduction in depression scores in the intervention group compared with the control group (MD = − 6.20, 95% CI: −7.64 to − 4.76). At 4 weeks, three comparisons were included. Wang (2025) and Zhu (2024) yielded a pooled mean difference of − 2.74 (95% CI: −9.67 to 4.19), with high heterogeneity. At 6 weeks, Wang (2025) reported a significant reduction (MD = − 5.60, 95% CI: −7.23 to − 3.97), favoring the intervention. At 8 weeks, Zhu (2024) observed a smaller mean difference (MD = − 0.18, 95% CI: −1.16 to 0.80), indicating no statistically significant difference between groups at this time point, as shown in Fig. 8 . 4.4.4 Anxiety Scores Anxiety scores were reported in four study arms (n = 408; 204 in the tACS group and 204 in the sham group). Compared with the control group, the intervention produced a significant reduction in anxiety scores (MD = − 3.48, 95% CI: −6.26 to − 0.70, p = 0.0142), with considerable heterogeneity across studies (I² = 93.0%, p < 0.0001). The effect of the intervention was further assessed at follow-up periods of 2, 4, 6, and 8 weeks. At 2 weeks, Wang (2025) reported a marked reduction in anxiety scores in the intervention group compared with the control group (MD = − 6.00, 95% CI: −7.89 to − 4.11). At 4 weeks, two comparisons (Wang 2025; Zhu 2024) yielded a pooled mean difference of − 2.74 (95% CI: −8.87 to 3.40), suggesting a trend toward improvement in the intervention group but with substantial variability between studies. At 6 weeks, Wang (2025) reported a significant reduction (MD = − 5.60, 95% CI: −7.80 to − 3.40), favoring the intervention. At 8 weeks, Zhu (2024) reported a smaller effect size (MD = − 0.65, 95% CI: −1.74 to 0.44), indicating no statistically significant difference between groups at this time point, as shown in Fig. 9 . 4.4.5 Remission Rate The remission rate was assessed in four study arms (n = 228; 114 in the tACS group and 114 in the sham group). Compared with the control group, the intervention significantly increased the remission rate (RR = 6.79, 95% CI: 2.12 to 21.71, p = 0.0012), with moderate heterogeneity across studies (I² = 53.1%, p = 0.0940). The effect of the intervention was further examined at follow-up periods of 2, 4, and 6 weeks. At 2 weeks, Wang (2025) reported a substantial increase in remission in the intervention group compared with the control group (RR = 15.00, 95% CI: 2.12 to 105.99). At 4 weeks, two studies (Wang 2020; Wang 2025) yielded a pooled risk ratio of 4.33 (95% CI: 0.90 to 20.90), suggesting a trend toward higher remission with the intervention; however, the wide confidence interval included the null value. At 6 weeks, Wang (2025) again reported a notable increase in remission rates (RR = 12.00, 95% CI: 1.67 to 86.19), as shown in Fig. 10 . 4.4.6 Response Rate The response rate was reported in six study arms (n = 228; 114 in the intervention group and 114 in the control group). The intervention produced a significantly higher response rate compared with the control group (RR = 11.21, 95% CI: 3.20 to 39.23, p = 0.0002), with moderate heterogeneity observed across studies (I² = 61.2%, p = 0.0521). The effect on response rate was further assessed at follow-up periods of 2, 4, and 6 weeks. At 2 weeks, Wang (2025) reported a substantial increase in response rates in the intervention group compared with the control group (RR = 23.00, 95% CI: 3.33 to 158.84). At 4 weeks, two studies (Wang 2020; Wang 2025) showed a pooled risk ratio of 7.12 (95% CI: 1.26 to 40.29), again favoring the intervention. Moderate heterogeneity was present (I² = 66.4%, p = 0.0846). At 6 weeks, Wang (2025) reported a continued benefit, with a risk ratio of 20.00 (95% CI: 2.88 to 139.02), as shown in Fig. 11 . 4.4.7 Adverse Events Adverse events were reported in three study arms (n = 168; 84 in the intervention group and 84 in the control group). Across all time points, there was no significant difference in the risk of adverse events between the intervention and control groups (RR = 1.06, 95% CI: 0.16 to 6.95, p = 0.9525), with no heterogeneity observed (I² = 0.0%, p = 0.3707). At 2 weeks, Wang (2025) reported a risk ratio of 2.00 (95% CI: 0.19 to 20.82), with a small number of events in both groups. At 4 weeks, the risk ratio was 0.33 (95% CI: 0.01 to 7.84), suggesting fewer adverse events in the intervention group, although the wide confidence interval reflects the limited number of events. No adverse events were reported at the 6-week follow-up, as shown in Fig. 12 . 4.5 Certainty of the evidence The certainty of the evidence for each outcome, assessed using the GRADE approach, is summarized in Table 4 . Evidence concerning improvements in Sleep Onset Latency (SOL) was rated as High certainty. Although the evidence was downgraded by one level due to moderate heterogeneity (I² = 46.9%), no other limitations (risk of bias, imprecision) were identified, and subgroup analyses addressed the inconsistency. Similarly, evidence for reductions in Daytime Disturbances was also High certainty, with no identified limitations across assessed domains (risk of bias, inconsistency, imprecision). Evidence for improvement in the Sleep Quality Sub-score was also assessed as High certainty; while downgraded one level for moderate heterogeneity (I² = 94.8%), no other limitations were present, and subgroup analyses were applied. Table 4 GRADE Evidence Profile for Outcomes in Chronic Insomnia Management Outcome No. of studies Risk of Bias Inconsistency Imprecision Publication of Bias Others Final Assessment Sleep Onset Latency (SOL) 4 No Downgraded by one level b No N/A Subgrouping analysis- Moderate heterogeneity High PSQI Total Score Reduction 4 No Downgraded by one level b No N/A Subgrouping analysis Moderate Total Sleep Time (TST) 4 No Downgraded by one level b No N/A Subgrouping analysis- significant heterogeneity Moderate Daytime Disturbances 3 No No No N/A None High Sleep Quality Sub- score 3 No Downgraded by one level b No N/A Subgrouping analysis- Moderate heterogeneity High Depression Scores 2 Downgraded by one level a Downgraded by one level b No N/A Subgrouping analysis- some concerns in randomization process Low Anxiety Scores 2 Downgraded by one level a Downgraded by one level b No N/A Subgrouping analysis- significant heterogeneity Low Remission Rate 2 No Downgraded by one level b Downgraded by one level c N/A Large effect size (RR)- Moderate heterogeneity Moderate Response Rate 2 No Downgraded by one level b Downgraded by one level c N/A Large effect size (RR) Moderate Adverse Events 1 Downgraded by one level a N/A Downgraded by one level c N/A Limited data- wide 95% CI Low Abbreviations: N/A, Not applicable due to small number of studies or insufficient data to assess heterogeneity or publication bias. a Owing to potential Risk of Bias due to concerns in randomization in the study by Wang 2025 b Owing to Presence of Heterogeneity in outcomes of ( Sleep Onset Latency, PSQI Total Score Reduction, Total Sleep Time, Sleep Quality Sub- score, Depression, anxiety Scores, remission and response rate . (I 2 = 46.9%, 91.5%, 96%, 94.8%,97.2%, 93%, 53.1% and 61.2%). c Owing to wide confidence intervals and small sample sizes; outcomes like (Remission, response rates and adverse events). Evidence for reductions in the PSQI Total Score and increases in Total Sleep Time (TST) was judged to be of Moderate certainty. Both outcomes were downgraded by one level due to significant heterogeneity (I² = 91.5% and 96%, respectively), mitigated by the application of subgroup analysis. No limitations were found for risk of bias or imprecision. Evidence for Remission Rate and Response Rate was also rated Moderate certainty. While both demonstrated large effect sizes (RR) and used subgroup analysis to address moderate heterogeneity (I² = 53.1% and 61.2%, respectively), each was downgraded by one level for imprecision, attributable to wide confidence intervals and small sample sizes. Evidence concerning reductions in Depression Scores and Anxiety Scores was assessed as Low certainty. Both outcomes were downgraded by one level for risk of bias (due to concerns in the randomization process in the Wang 2025 study) and by one level for substantial heterogeneity (I² = 97.2% and 93%, respectively). Subgroup analyses were performed but residual concerns remained. Evidence for Adverse Events was also rated Low certainty, being downgraded by one level for risk of bias (concerns in randomization in Wang 2025) and by one level for serious imprecision (wide 95% confidence intervals and small sample size). Discussion Transcranial alternating current stimulation (tACS) delivers rhythmic microcurrents to targeted cortical areas, simulating the brain’s natural oscillatory activity. It has recently been introduced into clinical treatment trials for neuropsychiatric disorders. Unlike transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS), which primarily modulate neural activity through excitation or inhibition, tACS is a distinct type of non-invasive brain stimulation that is simple, cost-effective, and safe. It allows for precise control by adjusting the phase, amplitude, and frequency of neural oscillations (Sun et al. 2025 ; Q. Zhou et al. 2021 ), enabling modification and entrainment of inherent oscillations through the injection of sinusoidal currents to the scalp, typically at frequencies ranging from 0.1 to 100 Hz (Elyamany et al. 2021 ; Tavakoli and Yun 2017). While cognitive behavioral therapy for insomnia (CBT-I) remains the gold-standard non-pharmacological intervention and pharmacotherapy (e.g., benzodiazepines, z-drugs) offers short-term symptomatic relief (Rossman 2019 ), transcranial alternating current stimulation (tACS) represents a mechanistically distinct neuromodulatory approach. Unlike CBT-I, which targets maladaptive sleep-related cognitions and behaviors, tACS directly modulates cortical oscillations implicated in sleep-wake regulation (Geffen, Bland, and Sale 2021). This is the first meta-analysis to evaluate both the efficacy and adverse events associated with tACS in patients with chronic insomnia. Our findings provide long-term evidence that tACS significantly improves key outcomes such as sleep quality, total sleep time (TST), and reduces daytime impairments, including symptoms of depression and anxiety, while maintaining a favorable safety profile. Sleep Quality Latency (SQL) is widely used in psychology, nursing, and medicine to refer to the duration needed to fall asleep, although a standardized definition is lacking (Sateia 2014 ). Our results showed that tACS significantly reduced SQL after two weeks of treatment; however, this improvement did not increase with therapy extension to eight weeks, suggesting that the primary benefit may occur during the initial treatment period. This aligns with Ayanampudi et al., who applied tACS at 5 Hz and 10 Hz for 15 minutes before sleep in 25 adults (13 with chronic insomnia), reporting significant improvements in TST and SQL, with a 28% reduction in SQL favoring personalized tACS (Ayanampudi et al. 2023 ). Similarly, Wang (2020) demonstrated that 20 sessions of 40-minute tACS significantly reduced SQL in patients with chronic insomnia. Another randomized controlled trial reported a 28% reduction in SQL compared with sham stimulation, suggesting that tACS facilitates faster sleep initiation via modulation of neural oscillations linked to sleep readiness (H. X. Wang et al. 2019 ; L. Wang et al. 2025). The Pittsburgh Sleep Quality Index (PSQI) is a 19-item self-report questionnaire assessing multiple aspects of sleep over the previous month, with higher scores indicating poorer sleep quality (Carpi 2025 ). Our study revealed significant PSQI reduction and subjective sleep quality improvement after 2, 4, and 6 weeks of tACS, with the largest effects at two weeks, sustained through week 6. The slightly lower effect at week 4 may be due to variability in patient characteristics. These findings are consistent with Shao et al., who showed that 5-Hz tACS significantly reduced PSQI in individuals with chronic insomnia (Shao et al. 2024 ), and with studies by Wang, Zhu, and Wang et al., which reported similar results across different frequencies and treatment durations (H. X. Wang et al. 2019 ; L. Wang et al. 2025; Zhu et al. 2024 ). Zhu et al. further demonstrated benefits in older patients, while Wang et al. reported more than a 50% PSQI reduction in the tACS group versus sham (Zhu et al. 2024 ). Total sleep time (TST) is the total duration of sleep across all stages (N1, N2, N3, and REM). It was significantly increased from baseline after two weeks of treatment, with sustained improvement in weeks 6 to 8 and moderate yet statistically significant gains at week 4. These results suggest that tACS induces rapid and sustained sleep restoration. Motamedi et al. reported increased TST after two 0.75-Hz tACS sessions in nine patients compared with sham (Motamedi et al. 2023 ). Ayanampudi, Wang, and Zhu et al. similarly reported increased TST, with Wang and Zhu showing gains of 102 and 33 minutes over controls, respectively (H. X. Wang et al. 2019 ; Zhu et al. 2024 ), and Ayanampudi reporting a 28% increase (Ayanampudi et al. 2023 ). Daytime disturbances such as fatigue, impaired concentration, and mood instability were also reduced after 2 to 8 weeks of tACS, with benefits evident by week 2. While Motamedi et al. observed improvements in sleep quality and TST after two short sessions (Motamedi et al. 2023 ), Wang et al. did not find significant changes in daytime disturbances (Zhu et al. 2024 ), suggesting that effects may be delayed. Zhu et al. also reported smaller reductions in daytime symptoms by week 8 (Ryan et al. 2023 ; H. X. Wang et al. 2019 ). These findings align with previous research demonstrating that neuromodulatory therapies can improve nocturnal sleep quality and daytime functioning in patients with insomnia or related conditions (Teruel-Hernández et al. 2023). Daytime disruptions, including fatigue, cognitive impairment, and mood disturbances, are common consequences of inadequate sleep, and their improvement is considered a clinically relevant outcome (Pearson et al. 2023 ). The Sleep Quality Subscore from the PSQI, which measures subjective sleep quality, improved significantly after two weeks and was maintained through eight weeks. This was consistent across RCTs and pilot studies using various stimulation protocols (Motamedi et al. 2023 ; Shao et al. 2024 ; L. Wang et al. 2025; Zhu et al. 2024 ). tACS significantly increased response rates compared to sham (RR = 11.21, 95% CI: 3.20–39.23, p = 0.0002; I² = 61.2%), with the largest short-term effects at 2 weeks (RR = 23.00) and sustained efficacy at 6 weeks (RR = 20.00) (H. X. Wang et al. 2019 ; L. Wang et al. 2025). These early improvements may reflect successful modulation of maladaptive brain oscillations via high-frequency tACS, consistent with dose–response patterns seen in tDCS and rTMS. However, a marked decline in response was observed beyond 8 to 14 weeks, suggesting the need for consolidation therapy. High-definition tACS (HD-tACS) offers more focal stimulation, potentially enhancing therapeutic effects compared to conventional electrode setups (Dondé et al. 2021 ; Herrero Babiloni et al. 2021 ; Kuo et al. 2013 ; Ma et al. 2021 ; Q. Zhou et al. 2020 ). Nevertheless, sham controls remain a methodological challenge, particularly with high-intensity, focal protocols where active and sham conditions may be distinguishable (Ambrus et al. 2012 ). tACS also increased depression remission rates versus sham (RR = 6.79, 95% CI: 2.12–21.71, p = 0.0012; I² = 53.1%), with the largest benefits at 2 and 6 weeks. Similar improvements were seen in anxiety scores, though benefits diminished by 8 weeks. This pattern suggests that acute modulation of cortical oscillations may yield early mood improvements that require maintenance strategies to persist (Brunoni et al. 2013 ; Hertenstein et al. 2019 ; Motamedi et al. 2023 ; Scott et al. 2021 ; D. Zhou et al. 2024 ). The overlap between neural circuits regulating sleep, mood, and anxiety may explain these effects (Bresser et al. 2020; Falgàs et al. 2021 ; Gruber and Cassoff 2014; Hong et al. 2021 ; Pace-Schott et al. 2017 ). Our meta-analysis found no significant difference in adverse event risk between tACS and sham (RR = 1.06, 95% CI: 0.16–6.95, p = 0.9525; I² = 0.0%). No phosphenes, somatosensory discomfort, headaches, dizziness, or nausea were reported (Elyamany et al. 2021 ; Fertonani, Ferrari, and Miniussi 2015; Matsumoto and Ugawa 2017). This aligns with the broader literature showing tACS to be safe, well-tolerated, and associated only with mild, transient sensations (Alexander et al. 2019 ; Latrèche et al. 2024 ; Wei et al. 2023 ). Several important limitations should be acknowledged. The number of included RCTs remains limited, sample sizes were often small, and substantial heterogeneity was present in stimulation protocols. High statistical inconsistency (I² = 46.9–97.2% for primary outcomes) reduces confidence in the precision and generalizability of the pooled effect estimates. This heterogeneity arises primarily from substantial variations in clinical application: the included trials employed markedly different tACS protocols with respect to stimulation frequency (0.75–10 Hz), intensity, session duration, electrode montage (e.g., frontal vs. parietal), and total treatment dose. In addition, differences in participant characteristics such as baseline insomnia severity, comorbidity profiles, and age distributions likely contributed to variable treatment responses. Although the random-effects model and subgroup analyses by time point were applied to account for this variability, the small number of studies (k = 4) precluded meaningful subgroup analyses based on stimulation parameters or patient subtypes, as well as the use of meta-regression to explore potential sources of heterogeneity. The reliance on subjective outcome measures and relatively short follow-up durations limits the ability to draw conclusions about long-term treatment durability. Methodological challenges, including difficulties in achieving effective blinding and variability in patient characteristics, further constrain interpretation. Future large-scale RCTs employing standardized, biologically informed stimulation protocols and rigorous participant stratification are needed to clarify the specific role of tACS in the management of chronic insomnia and to address key sources of uncertainty. Future research should prioritize strategies to extend the durability of tACS benefits beyond the acute treatment phase (2–6 weeks), during which maximal therapeutic effects have been observed. Booster session protocols warrant systematic investigation, modeled on successful paradigms in depression neuromodulation (e.g., weekly or monthly maintenance tACS following initial response), with optimization of timing, frequency, and dose-response relationships. Closed-loop systems that deliver stimulation contingent on real-time EEG biomarkers of hyperarousal or sleep-state transitions may enhance long-term efficacy by providing dynamic, state-dependent neuromodulation. Technical innovations such as high-definition tACS (HD-tACS) could improve precision in target engagement, while home-based tACS platforms may facilitate accessible maintenance therapy. Combination approaches integrating tACS with CBT-I or pharmacological agents also merit investigation to leverage potential synergistic effects on neural plasticity and sleep-wake regulation. Such trials should incorporate extended follow-up periods of at least 6 months, objective sleep monitoring with actigraphy or polysomnography, and patient-centered outcomes to rigorously assess the clinical sustainability of treatment effects. In summary, tACS appears to be an effective, non-invasive, and safe intervention for chronic insomnia, offering improvements in sleep parameters and short-term mood outcomes, with minimal side effects. The most prominent effects occur within the first 2 to 6 weeks, but long-term maintenance remains uncertain. Standardized protocols, objective sleep assessments, improved sham designs, and booster strategies are needed to optimize and sustain therapeutic benefits. Conclusion tACS represents a promising, well-tolerated, non-pharmacological intervention for chronic insomnia, offering rapid improvements in sleep quality, duration, initiation, and associated daytime impairments, alongside beneficial effects on mood. Future research should prioritize larger, methodologically rigorous trials featuring standardized stimulation protocols, longer follow-up durations, incorporation of objective sleep measures (e.g., polysomnography, actigraphy), optimized sham controls to minimize unblinding risk, and exploration of strategies (e.g., HD-tACS, booster sessions) to enhance and sustain the therapeutic gains observed primarily in the acute treatment phase. Declarations Authors' contributions: Yehia Nabil revised and organized the manuscript, reviewed its content, and oversaw study conceptualization, design, and protocol development, as well as abstract preparation. Salma Allam drafted the Introduction. Nourhan Hatem and Ahmad Alkheder contributed to study screening, data extraction, risk of bias assessment, and drafting of the Methods section. Anas Mansour conducted the statistical analysis and drafted the Results section. Menna Aboelkhier performed data extraction, risk of bias assessment, GRADE evaluation, and contributed to drafting the Discussion. Kholoud Elsamman participated in study screening and contributed to drafting the Discussion. Aya Samy carried out data extraction, risk of bias assessment, and prepared tables. Kiro Ehab and Ahmed Noufal performed data extraction, risk of bias assessment, and coordinated PRISMA reporting. All authors critically reviewed the manuscript, provided intellectual input, and approved the final version for submission. Conflict of interest: The authors declare that they have no conflict of interest. Disclosure: None of the authors received payments or services via his or her institution or from third parties. Ethical approval: This article does not contain human participants or animals performed. This is a review study and does not require ethical approval. Informed consent: Not applicable. this is systematic review study. 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09:10:09","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":26154,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of the mean difference in PSQI Total Score Reduction\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7420412/v1/9a4b26955f9360854a702fd7.png"},{"id":92580029,"identity":"c3dc32b6-e37b-4ac1-9f1e-15a9467fa0f1","added_by":"auto","created_at":"2025-10-01 09:10:08","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":30917,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of the mean difference in Total Sleep time (TST)\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7420412/v1/9c49b5426bc92845aa055060.png"},{"id":92579373,"identity":"1f266f96-d8c4-462e-a0a9-1a23b6ae7f5d","added_by":"auto","created_at":"2025-10-01 09:02:09","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":29842,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of the mean difference in Daytime Disturbances\u0026nbsp;\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-7420412/v1/df47c6b4ac1a89459c1212b0.png"},{"id":92580025,"identity":"69e5f09d-67dd-4424-9cb8-2062fdfdb9bf","added_by":"auto","created_at":"2025-10-01 09:10:08","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":30103,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of the mean difference in Sleep Quality Subscore\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-7420412/v1/b44423178333fd17b44367ec.png"},{"id":92580409,"identity":"d60950de-c317-4075-8331-134bb2c7debf","added_by":"auto","created_at":"2025-10-01 09:18:08","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":28383,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of the mean difference in Depression Scores\u003c/p\u003e","description":"","filename":"floatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-7420412/v1/d13eb5dabd978a7604ff3a33.png"},{"id":92579361,"identity":"f605d0e6-b9ee-437d-8146-b761a95701e6","added_by":"auto","created_at":"2025-10-01 09:02:08","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":28211,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of the mean difference in Anxiety Scores\u0026nbsp;\u003c/p\u003e","description":"","filename":"floatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-7420412/v1/df948d81cfd54116c4669121.png"},{"id":92579366,"identity":"fb73a82e-0a87-47f9-859e-4bbfc8dfd865","added_by":"auto","created_at":"2025-10-01 09:02:08","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":24299,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot for a meta-analysis of Remission Rates\u0026nbsp;\u003c/p\u003e","description":"","filename":"floatimage10.png","url":"https://assets-eu.researchsquare.com/files/rs-7420412/v1/4a3e28dd4644c7eccc226f5e.png"},{"id":92580031,"identity":"976a05aa-745e-4be5-b773-e7c2234cfbf0","added_by":"auto","created_at":"2025-10-01 09:10:09","extension":"png","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":24530,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot for a meta-analysis of Response Rates\u003c/p\u003e","description":"","filename":"floatimage11.png","url":"https://assets-eu.researchsquare.com/files/rs-7420412/v1/7e954590e2bb5a89fc384a9d.png"},{"id":92580410,"identity":"29a273b1-367f-4802-94a8-65d147b40db9","added_by":"auto","created_at":"2025-10-01 09:18:08","extension":"png","order_by":12,"title":"Figure 12","display":"","copyAsset":false,"role":"figure","size":18298,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot for a meta-analysis of Adverse Events\u003c/p\u003e","description":"","filename":"floatimage12.png","url":"https://assets-eu.researchsquare.com/files/rs-7420412/v1/2e43d5168fbd17baa4ce2b77.png"},{"id":103251316,"identity":"de123752-28c6-426b-9909-21fcfc32cb11","added_by":"auto","created_at":"2026-02-23 16:08:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2321570,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7420412/v1/f6229344-ecdf-477c-96f3-c1a9748539f5.pdf"},{"id":92579357,"identity":"c2349177-55f8-47d2-bc1b-63685c7a4c53","added_by":"auto","created_at":"2025-10-01 09:02:08","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":275242,"visible":true,"origin":"","legend":"","description":"","filename":"PRISMA2020checklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-7420412/v1/6b428a44284f3a3eee1acf60.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Transcranial Alternating Current Stimulation for Chronic Insomnia: A Meta-Analytic Evaluation of Sleep Restoration and Safety in Adults","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChronic insomnia is a prevalent sleep disorder that significantly affects both public health and individual well-being worldwide. It is characterized by persistent difficulty with sleep onset, maintenance, or quality despite adequate opportunity for rest, impacting a substantial proportion of adults (Bhaskar, Hemavathy, and Prasad 2016; Mai and Buysse 2008). Estimates suggest that up to 33% of adults may experience chronic insomnia (Benjafield et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2025\u003c/span\u003e), and approximately 12% of Americans have received a formal diagnosis (Academy of Sleep Medicine n.d.).\u003c/p\u003e\u003cp\u003eThe consequences of chronic insomnia extend beyond nighttime disturbances, contributing to increased risks of depression, anxiety, substance use disorders, motor vehicle accidents, and neurodegenerative conditions such as Alzheimer\u0026rsquo;s disease (Academy of Sleep Medicine n.d.; Mai and Buysse 2008). Its negative impact on health-related quality of life is comparable to that of other chronic medical conditions (Mai and Buysse \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2009\u003c/span\u003e). Individuals with more severe insomnia are at greater risk of persistent sleep difficulties over time (Morin et al. 2020).\u003c/p\u003e\u003cp\u003eCurrent treatment options have notable limitations. Pharmacological therapies can cause adverse effects, and adherence to cognitive behavioral therapy for insomnia (CBT-I) is often inconsistent. This has created growing interest in alternative and complementary treatments. Transcranial alternating current stimulation (tACS), a non-invasive brain stimulation technique, has emerged as a promising intervention for modulating brain oscillations and potentially restoring healthy sleep patterns (Lee et al. 2025; Motamedi et al. \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe core principle of tACS is the entrainment of endogenous brain rhythms, whereby externally applied alternating currents synchronize with and influence intrinsic neural oscillations (Tavakoli and Yun 2017; Wischnewski, Alekseichuk, and Opitz 2023). By adjusting the frequency, amplitude, and phase of the current, tACS can selectively target brain regions and modulate neuronal networks involved in sleep regulation (Agboada, Zhao, and Wischnewski 2025). For example, stimulation in the delta frequency range can induce and sustain slow-wave activity, which is essential for deep sleep (Ketz et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Takahashi et al. \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). This modulation of brain rhythms may promote neuroplastic changes and enhance cognitive processes such as sleep-dependent long-term memory consolidation (Ketz et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Lustenberger et al. \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2016\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn the context of insomnia, tACS has the potential to restore disrupted brain oscillations. Chronic insomnia is often associated with dysregulation of the sleep\u0026ndash;wake system, including alterations in brainwave patterns during both sleep and wakefulness. Applying tACS at specific frequencies may re-establish healthy oscillatory patterns, thereby improving sleep onset, continuity, and architecture. Some studies have reported enhancements in sleep architecture, including increased NREM stage 2 sleep (Dond\u0026eacute; et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2021\u003c/span\u003e), although the precise mechanisms remain incompletely understood.\u003c/p\u003e\u003cp\u003eThe growing body of research on tACS for insomnia, coupled with the shortcomings of current treatments, underscores the need for a comprehensive meta-analysis. While individual studies have demonstrated promising effects of tACS, such as increased total sleep time, reduced sleep onset latency, and improved sleep efficiency (Shao et al. \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Takeuchi et al. \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e2025\u003c/span\u003e), findings remain heterogeneous. Personalized stimulation frequencies appear more effective than fixed-frequency protocols in improving sleep quantity and facilitating sleep onset (Ayanampudi et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Furthermore, tACS has been shown to reduce cortical arousal by decreasing high-frequency EEG power, suggesting a direct influence on wakefulness-related neural activity (Shi et al. \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Improvements in sleep quality, efficiency, and insomnia severity have been particularly notable in older adults (Zhu et al. \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eImportantly, tACS has been associated with minimal adverse effects and may offer lasting therapeutic benefits (Q. Zhou et al. \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). This meta-analysis aims to systematically evaluate current evidence on tACS for chronic insomnia, assessing both subjective outcomes, such as the Pittsburgh Sleep Quality Index (PSQI), and objective metrics, including sleep onset latency (SOL), total sleep time (TST), and sleep efficiency. Adverse event rates and durability of benefits will also be examined to provide a thorough understanding of its safety and long-term efficacy. The results are intended to inform clinical decision-making, guide future research, and support the development of improved treatment strategies for adults with chronic insomnia.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Search Strategy and Data Sources\u003c/h2\u003e\u003cp\u003eWe conducted a systematic search of four electronic databases: PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials up to July 2025 to evaluate the efficacy and safety of transcranial alternating current stimulation (tACS) in adults with chronic insomnia. The search strategy incorporated the following terms and their relevant synonyms or MeSH terms: (\"transcranial alternating current stimulation\" OR tACS) AND (\"chronic insomnia\" OR \"persistent insomnia\" OR \"long-term insomnia\").\u003c/p\u003e\u003cp\u003eTwo independent reviewers screened study titles and abstracts using Rayyan to manage records, maintain blinding, and track conflicts (Ouzzani et al. \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Discrepancies were resolved by a third reviewer. Full texts of potentially eligible studies were retrieved for final inclusion.\u003c/p\u003e\u003cp\u003e This systematic review was conducted by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Page et al. \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). The review protocol was registered with PROSPERO, the international prospective register of systematic reviews (CRD420251121367).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Selection Criteria\u003c/h2\u003e\u003cp\u003eWe included studies that: (1) were randomized controlled trials (RCTs), non-randomized controlled trials, or crossover trials; (2) enrolled adults aged 18 years or older with a diagnosis of chronic insomnia; (3) evaluated transcranial alternating current stimulation (tACS) as the primary intervention; (4) reported at least one sleep-related outcome; and (5) were published in English.\u003c/p\u003e\u003cp\u003eStudies were excluded if they: (1) involved pediatric populations; (2) addressed acute or short-term insomnia; (3) combined tACS with other neurostimulation techniques without isolating the effect of tACS; (4) were case reports, editorials, protocols, or reviews; or (5) were animal or in vitro studies.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e3.3 Outcomes of interest included\u003c/h2\u003e\u003cp\u003eThe primary outcomes assessed in this review included Pittsburgh Sleep Quality Index (PSQI) total score reduction, response rate (defined as \u0026ge;\u0026thinsp;50% reduction in PSQI score), sleep onset latency (SOL), total sleep time (TST), and sleep efficiency (%).\u003c/p\u003e\u003cp\u003eSecondary outcomes included remission rate (defined as PSQI\u0026thinsp;\u0026lt;\u0026thinsp;5), sleep quality (specific PSQI components), daytime disturbances (PSQI components), adverse event (AE) rate, long-term durability of treatment effect (\u0026ge;\u0026thinsp;8 weeks), and changes in depression and anxiety scores measured by standardized scales, including the Hamilton Depression Rating Scale (HDRS or HAMD) and the Hamilton Anxiety Rating Scale (HARS or HAMA).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e\u003cb\u003e3.4 Quality Assessment and Data Extraction\u003c/b\u003e\u003c/h2\u003e\u003cp\u003eRelevant data from the included studies were extracted into a predefined online data extraction sheet. The extracted information included: (1) study characteristics; (2) baseline characteristics of the study population; (3) risk of bias domains; and (4) primary and secondary outcome measures.\u003c/p\u003e\u003cp\u003eThe risk of bias and methodological quality of the included studies were independently assessed by four reviewers using the Cochrane Risk of Bias 2.0 (RoB 2) tool for randomized controlled trials (Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ 2024; Sterne et al. \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). This tool evaluates five key domains: (1) the randomization process (selection bias); (2) deviations from intended interventions (performance bias); (3) outcome measurement (detection bias); (4) missing outcome data (attrition bias); and (5) selection of the reported results (reporting bias), while also considering other potential sources of bias.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e3.4 Data Synthesis and Statistical Analysis\u003c/h2\u003e\u003cp\u003eMeta-analyses were conducted using R software (version 4.5.1) with the meta package (version 1.17). A random-effects model (DerSimonian\u0026ndash;Laird method) was applied (DerSimonian and Laird 2015), and results were reported as mean differences (MDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, each with 95% confidence intervals (CIs). Continuous data (sample size, mean, and standard deviation) were analyzed using the metacont() function, and dichotomous data (events and total participants) were analyzed using the metabin() function.\u003c/p\u003e\u003cp\u003eSubgroup analyses were performed based on follow-up duration, grouping studies into 2-week, 4-week, 6-week, and 8-week time points to evaluate the effect of the intervention over time. Statistical heterogeneity was assessed using the I\u0026sup2; statistic, τ\u0026sup2;, and Cochran\u0026rsquo;s Q test, while subgroup differences were evaluated using χ\u0026sup2; tests.\u003c/p\u003e\u003cp\u003eNo sensitivity analyses or meta-regression were performed due to the small number of included studies, as these methods would have been ineffective and unlikely to alter the main findings.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.5 Certainty of Evidence Assessment\u003c/h2\u003e\u003cp\u003eWe assessed the certainty of evidence for each outcome using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach (Sch\u0026uuml;nemann et al. \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2008\u003c/span\u003e). The following domains were evaluated: risk of bias, inconsistency, imprecision, publication bias, and other considerations. For each outcome, the domains were summarized in an evidence profile table, which included the number of contributing studies, domain-specific ratings, and the final certainty rating.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e4.1 Study Selection and Characteristics\u003c/h2\u003e\u003cp\u003eThe systematic literature search identified 25 records from electronic databases (PubMed: n\u0026thinsp;=\u0026thinsp;7; Web of Science: n\u0026thinsp;=\u0026thinsp;10; Cochrane Library: n\u0026thinsp;=\u0026thinsp;8; Scopus: n\u0026thinsp;=\u0026thinsp;0). After the removal of 14 duplicate records, 11 unique records underwent title and abstract screening. Seven records were excluded at this stage. The full texts of the remaining four records were successfully retrieved and assessed for eligibility. No studies were excluded during the full-text assessment phase, as all met the predefined inclusion criteria. Consequently, four randomized controlled trials (RCTs) were included in the final systematic review as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe characteristics of the included studies are summarized in Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. All studies were parallel-group RCTs, except for Motamedi 2022, which employed a randomized single-crossover design. Sample sizes ranged from 9 to 120 participants (Total N\u0026thinsp;=\u0026thinsp;247). Three studies were conducted in China, while one was conducted in the USA. Study durations varied between 2 weeks and 8 weeks.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSummary of included studies\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"10\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy ID\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLocation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eStudy Design\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTotal Participants\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eIntervention\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDose\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eStudy Duration\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eFollow up Duration\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eOutcomes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eKey findings\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWang 2025\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003etACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 mA/ 10 HZ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e4\u0026ndash;6 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ePSQI, HAMD-17, HAMA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eSuperior sustained improvements in sleep quality, depression, anxiety, cognition\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eZhu 2024\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e120\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003etACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e15 mA/77.5 Hz\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e8 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ePSQI, SOL. TST, HAMD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eAge may influence treatment response\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMotamedi 2022\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUSA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003erandomized single-crossover trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003etACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.75 mA / .0.75 Hz\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e6 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eWASO, Sleep onset latency, QoL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNon-significant reduction in sleep onset latency and WASO\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWang 2019\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003etACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e15 mA/ 77.5 Hz\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e4 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eResponse rate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eWeek 8 response rate: 53.4% (16/30) vs 16.7% (5/30) (p\u0026thinsp;=\u0026thinsp;0.009)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"10\" nameend=\"c10\" namest=\"c1\"\u003e\u003cp\u003eRCT: Randomized Controlled Trial, tACS: Transcranial Alternating Current Stimulation, PSQI: Pittsburgh Sleep Quality Index, HAMD-17: Hamilton Depression Rating Scale-17, HAMA: Hamilton Anxiety Rating Scale, SOL: Sleep Onset Latency, TST: Total Sleep Time, WASO: Wake After Sleep Onset\u003c/p\u003e\u003cp\u003eQoL: Quality of Life\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eParticipants were adults with insomnia, diagnosed primarily using DSM-5 or ICSD-3 criteria. The mean age of participants across studies ranged from 48.6 to 55.3 years, with a higher proportion of females. Baseline insomnia duration showed considerable heterogeneity, ranging from a mean of 4.39 years to 58.1 years.\u003c/p\u003e\u003cp\u003eAll studies evaluated transcranial alternating current stimulation (tACS) as the active intervention compared to a sham control. Primary outcomes focused on sleep parameters, measured using the Pittsburgh Sleep Quality Index (PSQI), sleep onset latency (SOL), total sleep time (TST), wake after sleep onset (WASO), and sleep quality sub-scores. Secondary outcomes included depressive symptoms (Hamilton Depression Rating Scale, HAMD-17), anxiety symptoms (Hamilton Anxiety Rating Scale, HAMA), response rates, and quality of life (QoL) where assessed and illustrated in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Key baseline characteristics (age, sex distribution, diagnostic scores, insomnia duration) were generally well-balanced between intervention and sham groups within each study and shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline of the Characteristics of the included studies\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy ID\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSample size\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAge mean (SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eMales (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDiagnostic criteria (DSM-5, ICSD-3)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eInsomnia duration\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eWang 2025\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003etACS group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e50.2 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5 (17.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14.4 (2.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7 (4.44)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003esham\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e48.6 (14.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8 (28.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14.7 (2.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7 (4.44)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eZhu 2024\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003etACS group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e48.93 (12.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e19 (31.667%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13.85 (1.75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4.48 (5.70)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003esham\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e52.25 (10.38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23 (38.333%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13.77 (2.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4.39 (5.43)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eMotamedi 2022\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003etACS group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e50.2 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (11%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7.8 (3.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003esham\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e50.2 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (11%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7.8 (3.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eWang 2019\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003etACS group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e55.3 (8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8 (25.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13.26 (2.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e51.6 (46.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003esham\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e52.5 (10.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7 (22.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13.13 (1.59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e58.1 (80.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003eDSM-5: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, ICSD-3: International Classification of Sleep Disorders, 3rd Edition\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eOutcomes of included studies\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"18\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c17\" colnum=\"17\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c18\" colnum=\"18\"\u003e\u003c/div\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eStudy ID\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eTimepoint\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eTotal PSQI (post)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003ePSQI Total\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;8W\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003eSOL (min) (post)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003eTST (min) (post)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e\u003cp\u003eSleep quality\u003c/p\u003e\u003cp\u003eSub score\u003c/p\u003e\u003cp\u003e(post)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e\u003cp\u003eDaytime Disturbances (post)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u003cp\u003eHAMD\u003c/p\u003e\u003cp\u003e(post)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e\u003cp\u003eHAMA\u003c/p\u003e\u003cp\u003e(post)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003etACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSham\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003etACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSham\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003etACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eSham\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003etACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eSham\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003etACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eSham\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003etACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eSham\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003etACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eSham\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003etACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eSham\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u003cb\u003eWang 2025\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.4\u003c/p\u003e\u003cp\u003e(3.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13.7\u003c/p\u003e\u003cp\u003e(3.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e23.8\u003c/p\u003e\u003cp\u003e(16.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e80.7\u003c/p\u003e\u003cp\u003e(44.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e480\u003c/p\u003e\u003cp\u003e(54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e288\u003c/p\u003e\u003cp\u003e(42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003cp\u003e(0.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e2.2\u003c/p\u003e\u003cp\u003e(0.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003cp\u003e(0.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003cp\u003e(1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e3\u003c/p\u003e\u003cp\u003e(2.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e9.2\u003c/p\u003e\u003cp\u003e(2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e4\u003c/p\u003e\u003cp\u003e(3.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e10\u003c/p\u003e\u003cp\u003e(3.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.1\u003c/p\u003e\u003cp\u003e(4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13.6\u003c/p\u003e\u003cp\u003e(3.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e27.5\u003c/p\u003e\u003cp\u003e(16.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e83.2\u003c/p\u003e\u003cp\u003e(47.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e390\u003c/p\u003e\u003cp\u003e(60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e294\u003c/p\u003e\u003cp\u003e(36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.9\u003c/p\u003e\u003cp\u003e(0.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e2\u003c/p\u003e\u003cp\u003e(0.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003cp\u003e(0.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003cp\u003e(1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e3.1\u003c/p\u003e\u003cp\u003e(2.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e9.4\u003c/p\u003e\u003cp\u003e(2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e4.3\u003c/p\u003e\u003cp\u003e(3.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e10.2\u003c/p\u003e\u003cp\u003e(4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.3\u003c/p\u003e\u003cp\u003e(3.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13.6\u003c/p\u003e\u003cp\u003e(3.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e29.3\u003c/p\u003e\u003cp\u003e(20.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e81.8\u003c/p\u003e\u003cp\u003e(47.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e390\u003c/p\u003e\u003cp\u003e(66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e288\u003c/p\u003e\u003cp\u003e(36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.9\u003c/p\u003e\u003cp\u003e(0.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e2.1\u003c/p\u003e\u003cp\u003e(0.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.3\u003c/p\u003e\u003cp\u003e(0.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e1.4\u003c/p\u003e\u003cp\u003e(1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e38\u003c/p\u003e\u003cp\u003e(3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e9.4\u003c/p\u003e\u003cp\u003e(2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e4.8\u003c/p\u003e\u003cp\u003e(4.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e10.4\u003c/p\u003e\u003cp\u003e(4.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u003cb\u003eZhu 2024\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.85(1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13.77\u003c/p\u003e\u003cp\u003e(2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13.85\u003c/p\u003e\u003cp\u003e(1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13.77\u003c/p\u003e\u003cp\u003e(2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e93.25\u003c/p\u003e\u003cp\u003e(60.68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e79.67(53.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e208.8\u003c/p\u003e\u003cp\u003e(66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e240.6\u003c/p\u003e\u003cp\u003e(66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e5.23\u003c/p\u003e\u003cp\u003e(0.79)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e5.2\u003c/p\u003e\u003cp\u003e(0.88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e3.37\u003c/p\u003e\u003cp\u003e(1.31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e3.5\u003c/p\u003e\u003cp\u003e(1.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e7.13\u003c/p\u003e\u003cp\u003e(3.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e6.57\u003c/p\u003e\u003cp\u003e(3.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e7.25\u003c/p\u003e\u003cp\u003e(6.84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e6.63\u003c/p\u003e\u003cp\u003e(5.92)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.12\u003c/p\u003e\u003cp\u003e(3.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.58\u003c/p\u003e\u003cp\u003e(3.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e42.18\u003c/p\u003e\u003cp\u003e(37.69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e48.67\u003c/p\u003e\u003cp\u003e(41.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e361.2\u003c/p\u003e\u003cp\u003e(85.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e325.8\u003c/p\u003e\u003cp\u003e(70.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e2.67\u003c/p\u003e\u003cp\u003e(1.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e3.18\u003c/p\u003e\u003cp\u003e(1.55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1.3\u003c/p\u003e\u003cp\u003e(.083)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e2.23\u003c/p\u003e\u003cp\u003e(1.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e3.22\u003c/p\u003e\u003cp\u003e(2.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e2.45\u003c/p\u003e\u003cp\u003e(2.32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e3.58\u003c/p\u003e\u003cp\u003e(4.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e3.22\u003c/p\u003e\u003cp\u003e(4.29)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6.4\u003c/p\u003e\u003cp\u003e(3.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9.4\u003c/p\u003e\u003cp\u003e(3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e41.27\u003c/p\u003e\u003cp\u003e(38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e50.33\u003c/p\u003e\u003cp\u003e(49.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e350.4\u003c/p\u003e\u003cp\u003e(81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e317.4\u003c/p\u003e\u003cp\u003e(80.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e2.45\u003c/p\u003e\u003cp\u003e(1.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e3.55\u003c/p\u003e\u003cp\u003e(1.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1.52\u003c/p\u003e\u003cp\u003e(1.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e2.53\u003c/p\u003e\u003cp\u003e(1.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e2.42\u003c/p\u003e\u003cp\u003e(2.69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003e2.6\u003c/p\u003e\u003cp\u003e(2.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e2.42\u003c/p\u003e\u003cp\u003e(2.69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003e3.07\u003c/p\u003e\u003cp\u003e(3.34)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eMotamedi 2022\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.4\u003c/p\u003e\u003cp\u003e(2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e62\u003c/p\u003e\u003cp\u003e(40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e336\u003c/p\u003e\u003cp\u003e(48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e13.8\u003c/p\u003e\u003cp\u003e(9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.2\u003c/p\u003e\u003cp\u003e(4.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e37\u003c/p\u003e\u003cp\u003e(31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e39.9\u003c/p\u003e\u003cp\u003e(56.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e378\u003c/p\u003e\u003cp\u003e(72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003e10.3\u003c/p\u003e\u003cp\u003e(8.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eWang 2019\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 weeks intervention\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.93\u003c/p\u003e\u003cp\u003e(3.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.43\u003c/p\u003e\u003cp\u003e(3.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e31.2\u003c/p\u003e\u003cp\u003e(21.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e66.17\u003c/p\u003e\u003cp\u003e(50.23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e360.6\u003c/p\u003e\u003cp\u003e(96.41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e313.8\u003c/p\u003e\u003cp\u003e(75.52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e2.37\u003c/p\u003e\u003cp\u003e(1.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e3.4\u003c/p\u003e\u003cp\u003e(1.85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1.13\u003c/p\u003e\u003cp\u003e(0.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e1.37\u003c/p\u003e\u003cp\u003e(1.61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 weeks follow-up\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.73\u003c/p\u003e\u003cp\u003e(4.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.93\u003c/p\u003e\u003cp\u003e(4.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e38.5\u003c/p\u003e\u003cp\u003e(20.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e84.67\u003c/p\u003e\u003cp\u003e(65.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e343.2\u003c/p\u003e\u003cp\u003e(88.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e294\u003c/p\u003e\u003cp\u003e(96.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e5.13\u003c/p\u003e\u003cp\u003e(0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e4.93\u003c/p\u003e\u003cp\u003e(1.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e2.63\u003c/p\u003e\u003cp\u003e(1.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e3\u003c/p\u003e\u003cp\u003e(1.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c17\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c18\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e4.2 Risk of Bias of Included Studies\u003c/h2\u003e\u003cp\u003eThe risk of bias was assessed using the Cochrane RoB 2 tool across five domains. Two studies were judged to have a low overall risk of bias, supported by adequate randomization, allocation concealment, double-blinding, complete outcome data, appropriate outcome measurement methods, and adherence to pre-specified analysis plans (H. X. Wang et al. \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Zhu et al. \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTwo studies were rated as having some concerns (Motamedi et al. \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; L. Wang et al. 2025). In Wang et al. (2025), this was due to limited reporting on allocation concealment. In Motamedi et al. (2022), concerns arose from unclear randomization procedures, incomplete blinding of assessors, deviations from pre-specified analysis plans, and a small sample size.\u003c/p\u003e\u003cp\u003eOverall, the methodological quality was acceptable, with most studies demonstrating low risk in key domains such as outcome measurement, handling of missing data, and adherence to intended interventions. A visual summary of the risk of bias assessments is provided in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e4.3 Primary Outcomes\u003c/h2\u003e\u003cdiv id=\"Sec13\" class=\"Section3\"\u003e\u003ch2\u003e4.3.1 Sleep Onset Latency (SOL)\u003c/h2\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eSix studies reported a sleep quality subscore (n\u0026thinsp;=\u0026thinsp;234; 138 in the tACS group and 243 in the sham group). Compared with the control, the intervention was associated with a significant improvement in sleep quality (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;1.13, 95% CI: \u0026minus;1.38 to \u0026minus;\u0026thinsp;0.88, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), with moderate heterogeneity across studies (I\u0026sup2; = 46.9%, p\u0026thinsp;=\u0026thinsp;0.0935). The effect of the intervention was further examined at four follow-up time points: 2, 4, 6, and 8 weeks.\u003c/p\u003e\u003cp\u003eAt 2 weeks, a significant reduction in sleep onset latency (SOL) was observed (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;56.90, 95% CI: \u0026minus;74.44 to \u0026minus;\u0026thinsp;39.36), favoring the intervention group.\u003c/p\u003e\u003cp\u003eAt 4 weeks, three studies were included, yielding a pooled mean difference of \u0026minus;\u0026thinsp;52.20 (95% CI: \u0026minus;67.03 to \u0026minus;\u0026thinsp;37.37), significantly favoring the intervention, with no observed heterogeneity (I\u0026sup2; = 0%, p\u0026thinsp;=\u0026thinsp;0.5438).\u003c/p\u003e\u003cp\u003eAt 6 weeks, the pooled mean difference was \u0026minus;\u0026thinsp;31.36 (95% CI: \u0026minus;79.43 to 16.72), with substantial heterogeneity (I\u0026sup2; = 77.4%, p\u0026thinsp;=\u0026thinsp;0.0353). The 95% CI crossed the null, indicating no statistically significant effect.\u003c/p\u003e\u003cp\u003eAt 8 weeks, the effect size was smaller (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;9.06, 95% CI: \u0026minus;24.79 to 6.67), with no statistically significant difference between groups, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section3\"\u003e\u003ch2\u003e4.3.2 PSQI Total Score Reduction\u003c/h2\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe PSQI was reported in five studies (n\u0026thinsp;=\u0026thinsp;348; 174 in the tACS group and 174 in the sham group). Compared with the control, tACS produced a significant improvement in PSQI scores (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;5.73, 95% CI: \u0026minus;8.35 to \u0026minus;\u0026thinsp;3.10, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), with considerable heterogeneity (I\u0026sup2; = 91.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). The effect of the intervention was further evaluated at follow-up durations of 2, 4, and 6 weeks.\u003c/p\u003e\u003cp\u003eAt 2 weeks, a significant reduction in PSQI scores was observed (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;8.30, 95% CI: \u0026minus;10.08 to \u0026minus;\u0026thinsp;6.52), favoring the intervention group.\u003c/p\u003e\u003cp\u003eAt 4 weeks, three studies were included, yielding a pooled mean difference of \u0026minus;\u0026thinsp;4.35 (95% CI: \u0026minus;7.49 to \u0026minus;\u0026thinsp;1.21), also favoring the intervention, though with considerable heterogeneity (I\u0026sup2; = 90.2%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003c/p\u003e\u003cp\u003eAt 6 weeks, one study (Wang 2025) reported a significant reduction (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;7.30, 95% CI: \u0026minus;9.19 to \u0026minus;\u0026thinsp;5.41), with high heterogeneity (I\u0026sup2; = 91.5%).\u003c/p\u003e\u003cp\u003eThe test for subgroup differences between time points was not statistically significant (χ\u0026sup2; = 4.59, df\u0026thinsp;=\u0026thinsp;2, p\u0026thinsp;=\u0026thinsp;0.1006), suggesting that the effect of tACS on PSQI scores was relatively consistent across follow-up durations despite varying heterogeneity, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section3\"\u003e\u003ch2\u003e4.3.3 Total Sleep Time (TST)\u003c/h2\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eTotal sleep time (TST) was reported in six study arms (n\u0026thinsp;=\u0026thinsp;468; 234 in the tACS group and 234 in the sham group). Compared with the control group, the intervention produced a significant increase in TST (MD\u0026thinsp;=\u0026thinsp;85.29 minutes, 95% CI: 33.42 to 137.15, p\u0026thinsp;=\u0026thinsp;0.0013), although substantial heterogeneity was present (I\u0026sup2; = 94.8%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). The effect of the intervention was further examined at follow-up durations of 2, 4, 6, and 8 weeks.\u003c/p\u003e\u003cp\u003eAt 2 weeks, the intervention group demonstrated a significant increase in TST compared with the control group (MD\u0026thinsp;=\u0026thinsp;192.00 minutes, 95% CI: 166.66 to 217.34).\u003c/p\u003e\u003cp\u003eAt 4 weeks, three studies were included, yielding a pooled mean difference of 61.35 minutes (95% CI: 19.22 to 103.49), favoring the intervention, though with substantial heterogeneity (I\u0026sup2; = 80.5%, p\u0026thinsp;=\u0026thinsp;0.0060).\u003c/p\u003e\u003cp\u003eAt 6 weeks, Wang (2025) reported a significant increase in TST (MD\u0026thinsp;=\u0026thinsp;102.00 minutes, 95% CI: 74.15 to 129.85).\u003c/p\u003e\u003cp\u003eAt 8 weeks, Zhu (2024) reported an increase of 33.00 minutes (95% CI: 4.12 to 61.88), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003e4.4 Secondary Outcomes\u003c/h2\u003e\u003cdiv id=\"Sec17\" class=\"Section3\"\u003e\u003ch2\u003e4.4.1 Daytime Disturbances\u003c/h2\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eSix study arms reported daytime disturbances (n\u0026thinsp;=\u0026thinsp;468; 234 in the tACS group and 234 in the sham group). Compared with the control group, the intervention significantly reduced daytime disturbances (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.94, 95% CI: \u0026minus;1.13 to \u0026minus;\u0026thinsp;0.76, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), with low heterogeneity across studies (I\u0026sup2; = 6.0%, p\u0026thinsp;=\u0026thinsp;0.378). The effect of the intervention was further assessed at follow-up durations of 2, 4, 6, and 8 weeks.\u003c/p\u003e\u003cp\u003eAt 2 weeks, Wang (2025) reported a significant reduction in daytime disturbances in the intervention group compared with the control group (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;1.00, 95% CI: \u0026minus;1.45 to \u0026minus;\u0026thinsp;0.55).\u003c/p\u003e\u003cp\u003eAt 4 weeks, three studies were included, yielding a pooled mean difference of \u0026minus;\u0026thinsp;0.79 (95% CI: \u0026minus;1.19 to \u0026minus;\u0026thinsp;0.39), favoring the intervention, with moderate heterogeneity (I\u0026sup2; = 50.1%, p\u0026thinsp;=\u0026thinsp;0.135).\u003c/p\u003e\u003cp\u003eAt 6 weeks, Wang (2025) reported a significant reduction (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;1.10, 95% CI: \u0026minus;1.51 to \u0026minus;\u0026thinsp;0.69).\u003c/p\u003e\u003cp\u003eAt 8 weeks, Zhu (2024) found lower daytime disturbance scores in the intervention group compared with the control group (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;1.01, 95% CI: \u0026minus;1.43 to \u0026minus;\u0026thinsp;0.59), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e6\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section3\"\u003e\u003ch2\u003e4.4.2 Sleep Quality Subscore\u003c/h2\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe sleep quality subscore was reported in six study arms (n\u0026thinsp;=\u0026thinsp;468; 234 in the tACS group and 234 in the sham group). Compared with the control group, the intervention resulted in a significant improvement in sleep quality (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;1.13, 95% CI: \u0026minus;1.38 to \u0026minus;\u0026thinsp;0.88, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), with moderate heterogeneity across studies (I\u0026sup2; = 46.9%, p\u0026thinsp;=\u0026thinsp;0.0935). The effect of the intervention was further examined at follow-up time points of 2, 4, 6, and 8 weeks.\u003c/p\u003e\u003cp\u003eAt 2 weeks, Wang (2025) reported a marked improvement in the intervention group compared with the control group (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;1.50, 95% CI: \u0026minus;1.84 to \u0026minus;\u0026thinsp;1.16).\u003c/p\u003e\u003cp\u003eAt 4 weeks, three studies were included, yielding a pooled mean difference of \u0026minus;\u0026thinsp;0.90 (95% CI: \u0026minus;1.30 to \u0026minus;\u0026thinsp;0.51), favoring the intervention, with moderate heterogeneity (I\u0026sup2; = 39.6%, p\u0026thinsp;=\u0026thinsp;0.1912).\u003c/p\u003e\u003cp\u003eAt 6 weeks, Wang (2025) also reported a significant improvement (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;1.20, 95% CI: \u0026minus;1.54 to \u0026minus;\u0026thinsp;0.86).\u003c/p\u003e\u003cp\u003eAt 8 weeks, Zhu (2024) found sustained benefits, with the intervention group continuing to show lower scores (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;1.10, 95% CI: \u0026minus;1.69 to \u0026minus;\u0026thinsp;0.51), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig13\" class=\"InternalRef\"\u003e7\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section3\"\u003e\u003ch2\u003e4.4.3 Depression Scores\u003c/h2\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eDepression scores were reported in four study arms (n\u0026thinsp;=\u0026thinsp;408; 204 in the tACS group and 204 in the sham group). Compared with the control group, the intervention resulted in a significant reduction in depression scores (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;3.46, 95% CI: \u0026minus;6.61 to \u0026minus;\u0026thinsp;0.30, p\u0026thinsp;=\u0026thinsp;0.0319), with considerable heterogeneity across studies (I\u0026sup2; = 97.2%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). The effect of the intervention was further examined at follow-up durations of 2, 4, 6, and 8 weeks.\u003c/p\u003e\u003cp\u003eAt 2 weeks, Wang (2025) reported a notable reduction in depression scores in the intervention group compared with the control group (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;6.20, 95% CI: \u0026minus;7.64 to \u0026minus;\u0026thinsp;4.76).\u003c/p\u003e\u003cp\u003eAt 4 weeks, three comparisons were included. Wang (2025) and Zhu (2024) yielded a pooled mean difference of \u0026minus;\u0026thinsp;2.74 (95% CI: \u0026minus;9.67 to 4.19), with high heterogeneity.\u003c/p\u003e\u003cp\u003eAt 6 weeks, Wang (2025) reported a significant reduction (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;5.60, 95% CI: \u0026minus;7.23 to \u0026minus;\u0026thinsp;3.97), favoring the intervention.\u003c/p\u003e\u003cp\u003eAt 8 weeks, Zhu (2024) observed a smaller mean difference (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.18, 95% CI: \u0026minus;1.16 to 0.80), indicating no statistically significant difference between groups at this time point, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig15\" class=\"InternalRef\"\u003e8\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section3\"\u003e\u003ch2\u003e4.4.4 Anxiety Scores\u003c/h2\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAnxiety scores were reported in four study arms (n\u0026thinsp;=\u0026thinsp;408; 204 in the tACS group and 204 in the sham group). Compared with the control group, the intervention produced a significant reduction in anxiety scores (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;3.48, 95% CI: \u0026minus;6.26 to \u0026minus;\u0026thinsp;0.70, p\u0026thinsp;=\u0026thinsp;0.0142), with considerable heterogeneity across studies (I\u0026sup2; = 93.0%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). The effect of the intervention was further assessed at follow-up periods of 2, 4, 6, and 8 weeks.\u003c/p\u003e\u003cp\u003eAt 2 weeks, Wang (2025) reported a marked reduction in anxiety scores in the intervention group compared with the control group (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;6.00, 95% CI: \u0026minus;7.89 to \u0026minus;\u0026thinsp;4.11).\u003c/p\u003e\u003cp\u003eAt 4 weeks, two comparisons (Wang 2025; Zhu 2024) yielded a pooled mean difference of \u0026minus;\u0026thinsp;2.74 (95% CI: \u0026minus;8.87 to 3.40), suggesting a trend toward improvement in the intervention group but with substantial variability between studies.\u003c/p\u003e\u003cp\u003eAt 6 weeks, Wang (2025) reported a significant reduction (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;5.60, 95% CI: \u0026minus;7.80 to \u0026minus;\u0026thinsp;3.40), favoring the intervention.\u003c/p\u003e\u003cp\u003eAt 8 weeks, Zhu (2024) reported a smaller effect size (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.65, 95% CI: \u0026minus;1.74 to 0.44), indicating no statistically significant difference between groups at this time point, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig17\" class=\"InternalRef\"\u003e9\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec21\" class=\"Section3\"\u003e\u003ch2\u003e4.4.5 Remission Rate\u003c/h2\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe remission rate was assessed in four study arms (n\u0026thinsp;=\u0026thinsp;228; 114 in the tACS group and 114 in the sham group). Compared with the control group, the intervention significantly increased the remission rate (RR\u0026thinsp;=\u0026thinsp;6.79, 95% CI: 2.12 to 21.71, p\u0026thinsp;=\u0026thinsp;0.0012), with moderate heterogeneity across studies (I\u0026sup2; = 53.1%, p\u0026thinsp;=\u0026thinsp;0.0940). The effect of the intervention was further examined at follow-up periods of 2, 4, and 6 weeks.\u003c/p\u003e\u003cp\u003eAt 2 weeks, Wang (2025) reported a substantial increase in remission in the intervention group compared with the control group (RR\u0026thinsp;=\u0026thinsp;15.00, 95% CI: 2.12 to 105.99).\u003c/p\u003e\u003cp\u003eAt 4 weeks, two studies (Wang 2020; Wang 2025) yielded a pooled risk ratio of 4.33 (95% CI: 0.90 to 20.90), suggesting a trend toward higher remission with the intervention; however, the wide confidence interval included the null value.\u003c/p\u003e\u003cp\u003eAt 6 weeks, Wang (2025) again reported a notable increase in remission rates (RR\u0026thinsp;=\u0026thinsp;12.00, 95% CI: 1.67 to 86.19), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig19\" class=\"InternalRef\"\u003e10\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec22\" class=\"Section3\"\u003e\u003ch2\u003e4.4.6 Response Rate\u003c/h2\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe response rate was reported in six study arms (n\u0026thinsp;=\u0026thinsp;228; 114 in the intervention group and 114 in the control group). The intervention produced a significantly higher response rate compared with the control group (RR\u0026thinsp;=\u0026thinsp;11.21, 95% CI: 3.20 to 39.23, p\u0026thinsp;=\u0026thinsp;0.0002), with moderate heterogeneity observed across studies (I\u0026sup2; = 61.2%, p\u0026thinsp;=\u0026thinsp;0.0521). The effect on response rate was further assessed at follow-up periods of 2, 4, and 6 weeks.\u003c/p\u003e\u003cp\u003eAt 2 weeks, Wang (2025) reported a substantial increase in response rates in the intervention group compared with the control group (RR\u0026thinsp;=\u0026thinsp;23.00, 95% CI: 3.33 to 158.84).\u003c/p\u003e\u003cp\u003eAt 4 weeks, two studies (Wang 2020; Wang 2025) showed a pooled risk ratio of 7.12 (95% CI: 1.26 to 40.29), again favoring the intervention. Moderate heterogeneity was present (I\u0026sup2; = 66.4%, p\u0026thinsp;=\u0026thinsp;0.0846).\u003c/p\u003e\u003cp\u003eAt 6 weeks, Wang (2025) reported a continued benefit, with a risk ratio of 20.00 (95% CI: 2.88 to 139.02), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig21\" class=\"InternalRef\"\u003e11\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec23\" class=\"Section3\"\u003e\u003ch2\u003e4.4.7 Adverse Events\u003c/h2\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAdverse events were reported in three study arms (n\u0026thinsp;=\u0026thinsp;168; 84 in the intervention group and 84 in the control group). Across all time points, there was no significant difference in the risk of adverse events between the intervention and control groups (RR\u0026thinsp;=\u0026thinsp;1.06, 95% CI: 0.16 to 6.95, p\u0026thinsp;=\u0026thinsp;0.9525), with no heterogeneity observed (I\u0026sup2; = 0.0%, p\u0026thinsp;=\u0026thinsp;0.3707).\u003c/p\u003e\u003cp\u003eAt 2 weeks, Wang (2025) reported a risk ratio of 2.00 (95% CI: 0.19 to 20.82), with a small number of events in both groups.\u003c/p\u003e\u003cp\u003eAt 4 weeks, the risk ratio was 0.33 (95% CI: 0.01 to 7.84), suggesting fewer adverse events in the intervention group, although the wide confidence interval reflects the limited number of events.\u003c/p\u003e\u003cp\u003eNo adverse events were reported at the 6-week follow-up, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig23\" class=\"InternalRef\"\u003e12\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003e4.5 Certainty of the evidence\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe certainty of the evidence for each outcome, assessed using the GRADE approach, is summarized in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Evidence concerning improvements in \u003cb\u003eSleep Onset Latency (SOL)\u003c/b\u003e was rated as \u003cb\u003eHigh\u003c/b\u003e certainty. Although the evidence was downgraded by one level due to moderate heterogeneity (I\u0026sup2; = 46.9%), no other limitations (risk of bias, imprecision) were identified, and subgroup analyses addressed the inconsistency. Similarly, evidence for reductions in \u003cb\u003eDaytime Disturbances\u003c/b\u003e was also \u003cb\u003eHigh\u003c/b\u003e certainty, with no identified limitations across assessed domains (risk of bias, inconsistency, imprecision). Evidence for improvement in the \u003cb\u003eSleep Quality Sub-score\u003c/b\u003e was also assessed as \u003cb\u003eHigh\u003c/b\u003e certainty; while downgraded one level for moderate heterogeneity (I\u0026sup2; = 94.8%), no other limitations were present, and subgroup analyses were applied.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eGRADE Evidence Profile for Outcomes in Chronic Insomnia Management\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOutcome\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo. of studies\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRisk of Bias\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eInconsistency\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eImprecision\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePublication of Bias\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eFinal Assessment\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSleep Onset Latency (SOL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDowngraded by one level \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSubgrouping analysis- Moderate heterogeneity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eHigh\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePSQI Total Score Reduction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDowngraded by one level \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSubgrouping analysis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eModerate\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal Sleep Time (TST)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDowngraded by one level \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSubgrouping analysis- significant heterogeneity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eModerate\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDaytime Disturbances\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eHigh\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSleep Quality Sub- score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDowngraded by one level \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSubgrouping analysis- Moderate heterogeneity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eHigh\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDepression Scores\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDowngraded by one level \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDowngraded by one level \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSubgrouping analysis- some concerns in randomization process\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnxiety Scores\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDowngraded by one level \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDowngraded by one level \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSubgrouping analysis- significant heterogeneity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRemission Rate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDowngraded by one level \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDowngraded by one level \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLarge effect size (RR)- Moderate heterogeneity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eModerate\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eResponse Rate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDowngraded by one level \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDowngraded by one level \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLarge effect size (RR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eModerate\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdverse Events\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDowngraded by one level \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDowngraded by one level \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLimited data- wide 95% CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAbbreviations: N/A, Not applicable due to small number of studies or insufficient data to assess heterogeneity or publication bias.\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003csup\u003e\u003cb\u003ea\u003c/b\u003e\u003c/sup\u003e \u003cb\u003eOwing to potential Risk of Bias due to concerns in randomization in the study by\u003c/b\u003e \u003cb\u003eWang 2025\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e \u003cb\u003eOwing to Presence of Heterogeneity in outcomes of ( Sleep Onset Latency, PSQI Total Score Reduction, Total Sleep Time, Sleep Quality Sub- score, Depression, anxiety Scores, remission and response rate\u003c/b\u003e. \u003cb\u003e(I\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;46.9%, 91.5%, 96%, 94.8%,97.2%, 93%, 53.1% and 61.2%).\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003csup\u003e\u003cb\u003ec\u003c/b\u003e\u003c/sup\u003e \u003cb\u003eOwing to wide confidence intervals and small sample sizes; outcomes like (Remission, response rates and adverse events).\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eEvidence for reductions in the \u003cb\u003ePSQI Total Score\u003c/b\u003e and increases in \u003cb\u003eTotal Sleep Time (TST)\u003c/b\u003e was judged to be of \u003cb\u003eModerate\u003c/b\u003e certainty. Both outcomes were downgraded by one level due to significant heterogeneity (I\u0026sup2; = 91.5% and 96%, respectively), mitigated by the application of subgroup analysis. No limitations were found for risk of bias or imprecision. Evidence for \u003cb\u003eRemission Rate\u003c/b\u003e and \u003cb\u003eResponse Rate\u003c/b\u003e was also rated \u003cb\u003eModerate\u003c/b\u003e certainty. While both demonstrated large effect sizes (RR) and used subgroup analysis to address moderate heterogeneity (I\u0026sup2; = 53.1% and 61.2%, respectively), each was downgraded by one level for imprecision, attributable to wide confidence intervals and small sample sizes.\u003c/p\u003e\u003cp\u003eEvidence concerning reductions in \u003cb\u003eDepression Scores\u003c/b\u003e and \u003cb\u003eAnxiety Scores\u003c/b\u003e was assessed as \u003cb\u003eLow\u003c/b\u003e certainty. Both outcomes were downgraded by one level for risk of bias (due to concerns in the randomization process in the Wang 2025 study) and by one level for substantial heterogeneity (I\u0026sup2; = 97.2% and 93%, respectively). Subgroup analyses were performed but residual concerns remained. Evidence for \u003cb\u003eAdverse Events\u003c/b\u003e was also rated \u003cb\u003eLow\u003c/b\u003e certainty, being downgraded by one level for risk of bias (concerns in randomization in Wang 2025) and by one level for serious imprecision (wide 95% confidence intervals and small sample size).\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eTranscranial alternating current stimulation (tACS) delivers rhythmic microcurrents to targeted cortical areas, simulating the brain\u0026rsquo;s natural oscillatory activity. It has recently been introduced into clinical treatment trials for neuropsychiatric disorders. Unlike transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS), which primarily modulate neural activity through excitation or inhibition, tACS is a distinct type of non-invasive brain stimulation that is simple, cost-effective, and safe. It allows for precise control by adjusting the phase, amplitude, and frequency of neural oscillations (Sun et al. \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Q. Zhou et al. \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e2021\u003c/span\u003e), enabling modification and entrainment of inherent oscillations through the injection of sinusoidal currents to the scalp, typically at frequencies ranging from 0.1 to 100 Hz (Elyamany et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Tavakoli and Yun 2017).\u003c/p\u003e\u003cp\u003eWhile cognitive behavioral therapy for insomnia (CBT-I) remains the gold-standard non-pharmacological intervention and pharmacotherapy (e.g., benzodiazepines, z-drugs) offers short-term symptomatic relief (Rossman \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e2019\u003c/span\u003e), transcranial alternating current stimulation (tACS) represents a mechanistically distinct neuromodulatory approach. Unlike CBT-I, which targets maladaptive sleep-related cognitions and behaviors, tACS directly modulates cortical oscillations implicated in sleep-wake regulation (Geffen, Bland, and Sale 2021).\u003c/p\u003e\u003cp\u003eThis is the first meta-analysis to evaluate both the efficacy and adverse events associated with tACS in patients with chronic insomnia. Our findings provide long-term evidence that tACS significantly improves key outcomes such as sleep quality, total sleep time (TST), and reduces daytime impairments, including symptoms of depression and anxiety, while maintaining a favorable safety profile.\u003c/p\u003e\u003cp\u003eSleep Quality Latency (SQL) is widely used in psychology, nursing, and medicine to refer to the duration needed to fall asleep, although a standardized definition is lacking (Sateia \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). Our results showed that tACS significantly reduced SQL after two weeks of treatment; however, this improvement did not increase with therapy extension to eight weeks, suggesting that the primary benefit may occur during the initial treatment period. This aligns with Ayanampudi et al., who applied tACS at 5 Hz and 10 Hz for 15 minutes before sleep in 25 adults (13 with chronic insomnia), reporting significant improvements in TST and SQL, with a 28% reduction in SQL favoring personalized tACS (Ayanampudi et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Similarly, Wang (2020) demonstrated that 20 sessions of 40-minute tACS significantly reduced SQL in patients with chronic insomnia. Another randomized controlled trial reported a 28% reduction in SQL compared with sham stimulation, suggesting that tACS facilitates faster sleep initiation via modulation of neural oscillations linked to sleep readiness (H. X. Wang et al. \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; L. Wang et al. 2025).\u003c/p\u003e\u003cp\u003eThe Pittsburgh Sleep Quality Index (PSQI) is a 19-item self-report questionnaire assessing multiple aspects of sleep over the previous month, with higher scores indicating poorer sleep quality (Carpi \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Our study revealed significant PSQI reduction and subjective sleep quality improvement after 2, 4, and 6 weeks of tACS, with the largest effects at two weeks, sustained through week 6. The slightly lower effect at week 4 may be due to variability in patient characteristics. These findings are consistent with Shao et al., who showed that 5-Hz tACS significantly reduced PSQI in individuals with chronic insomnia (Shao et al. \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2024\u003c/span\u003e), and with studies by Wang, Zhu, and Wang et al., which reported similar results across different frequencies and treatment durations (H. X. Wang et al. \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; L. Wang et al. 2025; Zhu et al. \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Zhu et al. further demonstrated benefits in older patients, while Wang et al. reported more than a 50% PSQI reduction in the tACS group versus sham (Zhu et al. \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTotal sleep time (TST) is the total duration of sleep across all stages (N1, N2, N3, and REM). It was significantly increased from baseline after two weeks of treatment, with sustained improvement in weeks 6 to 8 and moderate yet statistically significant gains at week 4. These results suggest that tACS induces rapid and sustained sleep restoration. Motamedi et al. reported increased TST after two 0.75-Hz tACS sessions in nine patients compared with sham (Motamedi et al. \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Ayanampudi, Wang, and Zhu et al. similarly reported increased TST, with Wang and Zhu showing gains of 102 and 33 minutes over controls, respectively (H. X. Wang et al. \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Zhu et al. \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2024\u003c/span\u003e), and Ayanampudi reporting a 28% increase (Ayanampudi et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDaytime disturbances such as fatigue, impaired concentration, and mood instability were also reduced after 2 to 8 weeks of tACS, with benefits evident by week 2. While Motamedi et al. observed improvements in sleep quality and TST after two short sessions (Motamedi et al. \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2023\u003c/span\u003e), Wang et al. did not find significant changes in daytime disturbances (Zhu et al. \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2024\u003c/span\u003e), suggesting that effects may be delayed. Zhu et al. also reported smaller reductions in daytime symptoms by week 8 (Ryan et al. \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; H. X. Wang et al. \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). These findings align with previous research demonstrating that neuromodulatory therapies can improve nocturnal sleep quality and daytime functioning in patients with insomnia or related conditions (Teruel-Hern\u0026aacute;ndez et al. 2023). Daytime disruptions, including fatigue, cognitive impairment, and mood disturbances, are common consequences of inadequate sleep, and their improvement is considered a clinically relevant outcome (Pearson et al. \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe Sleep Quality Subscore from the PSQI, which measures subjective sleep quality, improved significantly after two weeks and was maintained through eight weeks. This was consistent across RCTs and pilot studies using various stimulation protocols (Motamedi et al. \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Shao et al. \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; L. Wang et al. 2025; Zhu et al. \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e\u003cp\u003etACS significantly increased response rates compared to sham (RR\u0026thinsp;=\u0026thinsp;11.21, 95% CI: 3.20\u0026ndash;39.23, p\u0026thinsp;=\u0026thinsp;0.0002; I\u0026sup2; = 61.2%), with the largest short-term effects at 2 weeks (RR\u0026thinsp;=\u0026thinsp;23.00) and sustained efficacy at 6 weeks (RR\u0026thinsp;=\u0026thinsp;20.00) (H. X. Wang et al. \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; L. Wang et al. 2025). These early improvements may reflect successful modulation of maladaptive brain oscillations via high-frequency tACS, consistent with dose\u0026ndash;response patterns seen in tDCS and rTMS. However, a marked decline in response was observed beyond 8 to 14 weeks, suggesting the need for consolidation therapy. High-definition tACS (HD-tACS) offers more focal stimulation, potentially enhancing therapeutic effects compared to conventional electrode setups (Dond\u0026eacute; et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Herrero Babiloni et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Kuo et al. \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Ma et al. \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Q. Zhou et al. \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Nevertheless, sham controls remain a methodological challenge, particularly with high-intensity, focal protocols where active and sham conditions may be distinguishable (Ambrus et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2012\u003c/span\u003e).\u003c/p\u003e\u003cp\u003etACS also increased depression remission rates versus sham (RR\u0026thinsp;=\u0026thinsp;6.79, 95% CI: 2.12\u0026ndash;21.71, p\u0026thinsp;=\u0026thinsp;0.0012; I\u0026sup2; = 53.1%), with the largest benefits at 2 and 6 weeks. Similar improvements were seen in anxiety scores, though benefits diminished by 8 weeks. This pattern suggests that acute modulation of cortical oscillations may yield early mood improvements that require maintenance strategies to persist (Brunoni et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Hertenstein et al. \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Motamedi et al. \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Scott et al. \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; D. Zhou et al. \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). The overlap between neural circuits regulating sleep, mood, and anxiety may explain these effects (Bresser et al. 2020; Falg\u0026agrave;s et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Gruber and Cassoff 2014; Hong et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Pace-Schott et al. \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eOur meta-analysis found no significant difference in adverse event risk between tACS and sham (RR\u0026thinsp;=\u0026thinsp;1.06, 95% CI: 0.16\u0026ndash;6.95, p\u0026thinsp;=\u0026thinsp;0.9525; I\u0026sup2; = 0.0%). No phosphenes, somatosensory discomfort, headaches, dizziness, or nausea were reported (Elyamany et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Fertonani, Ferrari, and Miniussi 2015; Matsumoto and Ugawa 2017). This aligns with the broader literature showing tACS to be safe, well-tolerated, and associated only with mild, transient sensations (Alexander et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Latr\u0026egrave;che et al. \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Wei et al. \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eSeveral important limitations should be acknowledged. The number of included RCTs remains limited, sample sizes were often small, and substantial heterogeneity was present in stimulation protocols. High statistical inconsistency (I\u0026sup2; = 46.9\u0026ndash;97.2% for primary outcomes) reduces confidence in the precision and generalizability of the pooled effect estimates. This heterogeneity arises primarily from substantial variations in clinical application: the included trials employed markedly different tACS protocols with respect to stimulation frequency (0.75\u0026ndash;10 Hz), intensity, session duration, electrode montage (e.g., frontal vs. parietal), and total treatment dose.\u003c/p\u003e\u003cp\u003eIn addition, differences in participant characteristics such as baseline insomnia severity, comorbidity profiles, and age distributions likely contributed to variable treatment responses. Although the random-effects model and subgroup analyses by time point were applied to account for this variability, the small number of studies (k\u0026thinsp;=\u0026thinsp;4) precluded meaningful subgroup analyses based on stimulation parameters or patient subtypes, as well as the use of meta-regression to explore potential sources of heterogeneity. The reliance on subjective outcome measures and relatively short follow-up durations limits the ability to draw conclusions about long-term treatment durability. Methodological challenges, including difficulties in achieving effective blinding and variability in patient characteristics, further constrain interpretation.\u003c/p\u003e\u003cp\u003eFuture large-scale RCTs employing standardized, biologically informed stimulation protocols and rigorous participant stratification are needed to clarify the specific role of tACS in the management of chronic insomnia and to address key sources of uncertainty. Future research should prioritize strategies to extend the durability of tACS benefits beyond the acute treatment phase (2\u0026ndash;6 weeks), during which maximal therapeutic effects have been observed. Booster session protocols warrant systematic investigation, modeled on successful paradigms in depression neuromodulation (e.g., weekly or monthly maintenance tACS following initial response), with optimization of timing, frequency, and dose-response relationships.\u003c/p\u003e\u003cp\u003eClosed-loop systems that deliver stimulation contingent on real-time EEG biomarkers of hyperarousal or sleep-state transitions may enhance long-term efficacy by providing dynamic, state-dependent neuromodulation. Technical innovations such as high-definition tACS (HD-tACS) could improve precision in target engagement, while home-based tACS platforms may facilitate accessible maintenance therapy. Combination approaches integrating tACS with CBT-I or pharmacological agents also merit investigation to leverage potential synergistic effects on neural plasticity and sleep-wake regulation. Such trials should incorporate extended follow-up periods of at least 6 months, objective sleep monitoring with actigraphy or polysomnography, and patient-centered outcomes to rigorously assess the clinical sustainability of treatment effects.\u003c/p\u003e\u003cp\u003eIn summary, tACS appears to be an effective, non-invasive, and safe intervention for chronic insomnia, offering improvements in sleep parameters and short-term mood outcomes, with minimal side effects. The most prominent effects occur within the first 2 to 6 weeks, but long-term maintenance remains uncertain. Standardized protocols, objective sleep assessments, improved sham designs, and booster strategies are needed to optimize and sustain therapeutic benefits.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003etACS represents a promising, well-tolerated, non-pharmacological intervention for chronic insomnia, offering rapid improvements in sleep quality, duration, initiation, and associated daytime impairments, alongside beneficial effects on mood. Future research should prioritize larger, methodologically rigorous trials featuring standardized stimulation protocols, longer follow-up durations, incorporation of objective sleep measures (e.g., polysomnography, actigraphy), optimized sham controls to minimize unblinding risk, and exploration of strategies (e.g., HD-tACS, booster sessions) to enhance and sustain the therapeutic gains observed primarily in the acute treatment phase.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYehia Nabil\u003c/strong\u003e revised and organized the manuscript, reviewed its content, and oversaw study conceptualization, design, and protocol development, as well as abstract preparation. \u003cstrong\u003eSalma Allam\u003c/strong\u003e drafted the Introduction. \u003cstrong\u003eNourhan Hatem\u003c/strong\u003e \u003cstrong\u003eand Ahmad\u003c/strong\u003e \u003cstrong\u003eAlkheder\u003c/strong\u003e contributed to study screening, data extraction, risk of bias assessment, and drafting of the Methods section. \u003cstrong\u003eAnas Mansour\u003c/strong\u003e conducted the statistical analysis and drafted the Results section. \u003cstrong\u003eMenna Aboelkhier\u003c/strong\u003e performed data extraction, risk of bias assessment, GRADE evaluation, and contributed to drafting the Discussion. \u003cstrong\u003eKholoud Elsamman\u003c/strong\u003e participated in study screening and contributed to drafting the Discussion. \u003cstrong\u003eAya Samy\u003c/strong\u003e carried out data extraction, risk of bias assessment, and prepared tables. \u003cstrong\u003eKiro Ehab\u003c/strong\u003e \u003cstrong\u003eand Ahmed Noufal\u003c/strong\u003e performed data extraction, risk of bias assessment, and coordinated PRISMA reporting.\u003c/p\u003e\n\u003cp\u003eAll authors critically reviewed the manuscript, provided intellectual input, and approved the final version for submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure:\u0026nbsp;\u003c/strong\u003eNone of the authors received payments or services via his or her institution or from third parties.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u003c/strong\u003e This article does not contain human participants or animals performed. This is a review study and does not require ethical approval.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent:\u0026nbsp;\u003c/strong\u003eNot applicable. this is systematic review study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate declarations:\u003c/strong\u003e not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eAll authors' consent has been obtained by the corresponding author for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e No any funding.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAcademy of Sleep Medicine, American. \u0026ldquo;AASM Sleep Prioritization Survey Chronic Insomnia.\u0026rdquo;\u003c/li\u003e\n\u003cli\u003eAgboada, Desmond, Zhihe Zhao, and Miles Wischnewski. 2025. \u0026ldquo;Neuroplastic Effects of Transcranial Alternating Current Stimulation (TACS): From Mechanisms to Clinical Trials.\u0026rdquo; \u003cem\u003eFrontiers in Human Neuroscience\u003c/em\u003e 19: 1548478. doi:10.3389/FNHUM.2025.1548478/XML.\u003c/li\u003e\n\u003cli\u003eAlexander, Morgan L., Sankaraleengam Alagapan, Courtney E. 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\u003cem\u003eFrontiers in Psychiatry\u003c/em\u003e 14: 1308437. doi:10.3389/FPSYT.2023.1308437/XML.\u003c/li\u003e\n\u003cli\u003eWischnewski, Miles, Ivan Alekseichuk, and Alexander Opitz. 2023. \u0026ldquo;Neurocognitive, Physiological, and Biophysical Effects of Transcranial Alternating Current Stimulation.\u0026rdquo; \u003cem\u003eTrends in Cognitive Sciences\u003c/em\u003e 27(2): 189\u0026ndash;205. doi:10.1016/j.tics.2022.11.013.\u003c/li\u003e\n\u003cli\u003eZhou, Dongsheng, Xingxing Li, Shuochi Wei, Chang Yu, Dongmei Wang, Yuchen Li, Jiaxin Li, et al. 2024. \u0026ldquo;Transcranial Direct Current Stimulation Combined With Repetitive Transcranial Magnetic Stimulation for Depression: A Randomized Clinical Trial.\u0026rdquo; \u003cem\u003eJAMA network open\u003c/em\u003e 7(11): e2444306. doi:10.1001/JAMANETWORKOPEN.2024.44306,.\u003c/li\u003e\n\u003cli\u003eZhou, Qi, Gangqiao Qi, Jun Liu, Xi Mei, Xiaoli Liu, Xingxing Li, Wenhao Zhuang, Dongsheng Zhou, and Huifei Ge. 2021. \u0026ldquo;Chronic Insomnia: Treatment with Transcranial Alternating Current Stimulation.\u0026rdquo; \u003cem\u003eBrain Stimulation\u003c/em\u003e 14(4): 848\u0026ndash;50. doi:10.1016/j.brs.2021.05.007.\u003c/li\u003e\n\u003cli\u003eZhou, Qi, Chang Yu, Haihang Yu, Yuanyuan Zhang, Zhiwang Liu, Zhenyu Hu, Ti Fei Yuan, and Dongsheng Zhou. 2020. \u0026ldquo;The Effects of Repeated Transcranial Direct Current Stimulation on Sleep Quality and Depression Symptoms in Patients with Major Depression and Insomnia.\u0026rdquo; \u003cem\u003eSleep Medicine\u003c/em\u003e 70: 17\u0026ndash;26. doi:10.1016/j.sleep.2020.02.003.\u003c/li\u003e\n\u003cli\u003eZhu, Xiaolin, Yanping Ren, Shuping Tan, and Xin Ma. 2024. \u0026ldquo;Efficacy of Transcranial Alternating Current Stimulation in Treating Chronic Insomnia and the Impact of Age on Its Effectiveness: A Multisite Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study.\u0026rdquo; \u003cem\u003eJournal of Psychiatric Research\u003c/em\u003e 170: 253\u0026ndash;61. doi:10.1016/J.JPSYCHIRES.2023.12.037.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Transcranial alternating current stimulation, chronic insomnia, meta-analysis, sleep quality, randomized controlled trial, neuromodulation, Pittsburgh Sleep Quality Index, sleep onset latency","lastPublishedDoi":"10.21203/rs.3.rs-7420412/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7420412/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eChronic insomnia affects approximately one-third of adults globally, imposing substantial health burdens with limited effective treatments. Transcranial alternating current stimulation (tACS) emerges as a non-invasive neuromodulatory approach, though its efficacy and safety profile require systematic evaluation.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe systematically searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials through July 2025 for randomized controlled trials (RCTs) evaluating tACS in adults with chronic insomnia. Primary outcomes included Pittsburgh Sleep Quality Index (PSQI) scores, sleep onset latency (SOL), total sleep time (TST), and sleep efficiency. Secondary outcomes encompassed remission/response rates, daytime disturbances, mood symptoms, and adverse events. Data were pooled using random-effects models. Risk of bias and evidence certainty were assessed via Cochrane RoB 2.0 and GRADE.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eFour RCTs (n\u0026thinsp;=\u0026thinsp;247) were included. tACS significantly reduced SOL at 2 weeks (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;56.90 min; 95% CI: \u0026minus;74.44 to \u0026minus;\u0026thinsp;39.36) and 4 weeks (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;52.20 min; \u0026minus;67.03 to \u0026minus;\u0026thinsp;37.37), improved PSQI (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;5.73; \u0026minus;8.35 to \u0026minus;\u0026thinsp;3.10; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), increased TST (MD\u0026thinsp;=\u0026thinsp;+\u0026thinsp;85.29 min; 33.42 to 137.15; p\u0026thinsp;=\u0026thinsp;0.0013), and reduced daytime disturbances (MD\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.94; \u0026minus;1.13 to \u0026minus;\u0026thinsp;0.76; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Response rates favored tACS (RR\u0026thinsp;=\u0026thinsp;11.21; 3.20\u0026ndash;39.23; p\u0026thinsp;=\u0026thinsp;0.0002). Mood improvements were not sustained beyond 8 weeks. No significant adverse events emerged versus sham (RR\u0026thinsp;=\u0026thinsp;1.06; 0.16\u0026ndash;6.95). Heterogeneity ranged moderate-to-high (I\u0026sup2; = 46.9\u0026ndash;97.2%).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003etACS demonstrates rapid efficacy (2\u0026ndash;6 weeks) and safety for core insomnia symptoms. Sustained benefits require protocol optimization and long-term evaluation.\u003c/p\u003e","manuscriptTitle":"Transcranial Alternating Current Stimulation for Chronic Insomnia: A Meta-Analytic Evaluation of Sleep Restoration and Safety in Adults","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-01 09:02:03","doi":"10.21203/rs.3.rs-7420412/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-20T08:57:57+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-16T09:05:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"78525737079512128983437485885945806052","date":"2026-01-11T02:09:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-14T12:01:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"177173406398736229784270933137843474450","date":"2025-09-30T12:21:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-12T15:30:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-12T15:24:56+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-12T14:50:22+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-12T09:11:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Psychiatry","date":"2025-08-28T21:39:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4aeb0f37-79fc-4ca6-80f9-6f1fe34a3947","owner":[],"postedDate":"October 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-23T16:05:38+00:00","versionOfRecord":{"articleIdentity":"rs-7420412","link":"https://doi.org/10.1186/s12888-026-07900-w","journal":{"identity":"bmc-psychiatry","isVorOnly":false,"title":"BMC Psychiatry"},"publishedOn":"2026-02-19 15:58:38","publishedOnDateReadable":"February 19th, 2026"},"versionCreatedAt":"2025-10-01 09:02:03","video":"","vorDoi":"10.1186/s12888-026-07900-w","vorDoiUrl":"https://doi.org/10.1186/s12888-026-07900-w","workflowStages":[]},"version":"v1","identity":"rs-7420412","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7420412","identity":"rs-7420412","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}