Homeopathy for the Treatment of Insomnia: A Systematic Review and Meta-analysis

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Sumsuzzman, Daniel Wrzałko, Robbert van Haselen, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9439398/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Insomnia is a prevalent disorder associated with substantial impairment. Homeopathy has been proposed as a complementary treatment for insomnia, but its clinical effects remain uncertain. This systematic review assessed the efficacy, effectiveness, and safety of homeopathic treatments for insomnia. Methods : Prospective comparative studies evaluating any homeopathic preparation for insomnia were included. Searches in MEDLINE, EMBASE, seven additional databases, and three trial registries were conducted through August 2025. Risk of bias, intervention complexity, model validity, and pragmatism were assessed using respectively RoB 2, ROBINS-I, iCAT, MVHT, and RITES. Data were synthesized using random-effects meta-analyses, and certainty of evidence was evaluated using GRADE. Results : Eight randomized controlled trials (RCTs; n = 364 participants) and four non-randomized studies on interventions (NRSIs; n = 517) met the inclusion criteria. In adults, sleep quality (MD = −2.6 points; 95% CI −5.5 to 2.6; low certainty) and insomnia severity (MD = −3.2; 95% CI −5.68 to −0.72, moderate certainty) were reported in one RCT each. For total sleep time, the pooled MD of three RCTs was 0.65 hours (95% CI −0.9 to 2.2; low certainty). In children, one open-label RCT suggested a difference in insomnia severity, but certainty of evidence was very low. Adverse events were rarely reported, resulting in low certainty evidence. Conclusions : The current evidence is mainly limited by imprecision and risk of bias. The available evidence does not allow firm conclusions regarding the effects of homeopathy for insomnia. High-quality, replicated trials with systematic adverse-event monitoring are needed . Registration : Prospero 2025 CRD420251015627 Insomnia Homeopathy Systematic Review Meta-analysis Sleep disorders Funding: Software AG Stiftung Darmstadt Germany Figures Figure 1 INTRODUCTION Insomnia is a prevalent and disabling sleep disorder defined as persistent difficulty with sleep initiation, maintenance, or early-morning awakening despite adequate sleep opportunity, causing significant daytime distress and impairment [1-3]. Recent estimates suggest that insomnia affects 16.2% of adults globally, with 7.9% experiencing severe insomnia, and the highest burden observed among older adults, women, and individuals with comorbid medical or psychiatric conditions [4, 5]. Beyond individual suffering, chronic insomnia is increasingly recognized both as a clinical and a public health issue, contributing to impaired cognitive and physical functioning, increased risks for cardiovascular and metabolic diseases, reduced quality of life, and substantial societal costs including work absenteeism, productivity loss, and elevated healthcare utilization [4, 6, 7]. Clinical management of insomnia remains challenging despite advances in understanding its pathophysiology and an expanding array of interventions. Pharmacologic therapies, notably benzodiazepine receptor agonists, are commonly prescribed but raise concerns about tolerance, dependence, residual sedation, and cognitive impairment with long-term use [5]. Cognitive behavioural therapy for insomnia (CBT-I) is recommended as the first-line treatment, but implementation is hampered by restricted access, patient adherence barriers, and gradual response times [8]. These limitations have spurred interest in alternative or complementary therapies that may offer safer, accessible, and effective options for those who are refractory to, or prefer, nonpharmacologic strategies. Homeopathy, based on the principle of “treat likes by likes” and individualized use of highly diluted substances [9], is an alternative approach for insomnia treatment: The clinical evidence base remains inconsistent and subject to methodological criticism, such as small sample sizes, population heterogeneity, variable homeopathic preparations, and outcome measure inconsistency [10]. Current interest in integrating traditional, complementary and integrative medicine modalities into mainstream care, underscores the need for a rigorous, up-to-date evidence synthesis employing comprehensive search strategies and robust bias assessment tools. Earlier systematic reviews concluded that evidence for homeopathy in insomnia was unconvincing, but these reviews were conducted more than a decade ago and did not include quantitative synthesis or more recent trials and grey literature [10, 11]. Accordingly, this systematic review and outcome-specific meta-analysis updates and extends earlier syntheses to evaluate the efficacy, effectiveness and safety of homeopathic interventions for insomnia, adopting a complex systems perspective that incorporates patient involvement, model validity, and efficacy–effectiveness considerations [12]. METHODS This systematic review was conducted in accordance with the methodological guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions [13]. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement [14], the PRISMA-S extension for literature searches [15], and the GRIPP2 guideline for patient involvement [16]. The review protocol was prospectively registered in the PROSPERO database (registration number: CRD420251015627) in combination with a template protocol [14]. The present review adopts the template protocol in full [17], with insomnia-specific adaptations (see supp. 1 ). Literature search and study selection On February, 21st, 2025 (last update by rerunning all searches: 13.8.2025), we conducted a systematic literature search according to chapter 4 of the Cochrane Handbook of Systematic Reviews [18] and the PRESS peer review guideline [19]; one experienced reviewer (ML) and an information specialist (SK) were involved in the process. We searched databases (the HOMIS database [20], MEDLINE, EMBASE, CINAHL, LILACS, AMED, PsycInfo, Cochrane Library, Web of Science) from the beginning of the databases until February 20th, trial registries (clinicaltrials.gov, trialsearch.who.int, clinicaltrialsregister.eu), preprint servers (OSF, medRxiv), ProQuest Dissertations & Theses Citation Index and oatd.org for theses, as well as the Indian Ministry of AYUSH research portal (ayushportal.nic.in, google scholar). The search strategy combined terms regarding homeopathy, study design (randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs), and insomnia, without language or search filter restrictions. The search strategy was developed by one reviewer (ML) and checked by an information specialist (SK). Details of the search strategy are documented in supp. 2. Results from the literature searches were exported to Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia (available at www.covidence.org). After removal of duplicates, two reviewers (ML, SK) independently assessed study eligibility. Differences of opinion were resolved through discussion. Eligibility criteria Studies were eligible if they were prospective, comparative, and evaluated the efficacy, effectiveness, or safety of homeopathic preparations (HPs) in individuals with insomnia disorder. We included randomized controlled trials (RCTs) and prospective non-randomized studies of interventions (NRSIs) to capture both experimental and real-world evidence. Participants had insomnia as the condition under investigation. For study selection, insomnia was operationalized as a primary diagnosis of insomnia disorder, as reported by the study authors. This operationalization was used to distinguish studies in which insomnia was the index condition from populations treated for other primary conditions in which sleep or sleep quality was assessed only as a secondary outcome. All exclusions were documented. Interventions comprised any HP prepared in accordance with a nationally recognized homeopathic pharmacopoeia, administered by any route (e.g., oral, sublingual, topical). Both individualized (classical) and non-individualized homeopathy were eligible. Co-interventions were permitted if the comparator group received an identical regimen excluding the HMP, ensuring the specific effect of homeopathy could be isolated. Comparator arms included inactive controls (e.g., placebo, no treatment, waiting list) and active comparators (e.g., pharmacological agents, psychological therapies, or physical interventions). Studies were required to assess at least one clinical outcome at a minimum of two time points (pre- and post-intervention). Studies reporting only economic outcomes were excluded. We excluded retrospective designs, cross-sectional studies, uncontrolled before–after studies, interrupted time series, case series, case reports, and any study subject to retraction or formal expression of concern. A detailed summary of the inclusion and exclusion criteria is provided in supp. 3. No language restrictions or other limitations were applied. Details of studies excluded after full-text screening, including reasons for exclusion, are provided in supp. 4 , table S.3. Data-extraction Two reviewers (ML, DS) independently extracted data into Covidence using a structured codebook, describing the extracted variables. Variables included publication details (country, year), study design, participant demographics (mean age, gender, sample size, dropouts), intervention characteristics (type of homeopathy, potency, frequency), comparator type, duration of intervention, primary and secondary outcomes, effect size estimates, and funding sources. Discrepancies between reviewers were resolved through discussion. The codebook is provided in supp. 5. For each study, pre–post mean differences and their corresponding standard deviations were extracted for treatment and control groups and analysed as outcome measures. Further details on author contact are provided in Supp. 4 . Risk of bias To assess the risk of bias, the Cochrane risk-of-bias tool for randomized trials (RoB 2) was used for RCTs and its supplement for crossover trials [22] and Cochrane’s ROBINS-I V2 for NRSIs [23]. Assessments followed the standard domains and decision algorithms as specified in the respective tools. Studies were evaluated on an outcome-specific basis by two reviewers independently (ML, DS), and disagreements were resolved through discussion. Further assessments Model validity of RCTs was assessed using the MVHT instrument (overall judgement: inadequate, uncertain, acceptable) [24]. Two experienced physicians and homeopaths (AD, DW) rated all studies independently; disagreements were resolved by discussion mediated by a third reviewer (ML). To position trials on the efficacy–effectiveness continuum, we applied the RITES tool (scale from 1 to 5, with 1 = strong emphasis on efficacy and 5 = strong emphasis on effectiveness) [25]. The same reviewers (AD, DW) performed independent ratings; disagreements were resolved by discussion mediated by a third reviewer (ML). We applied a modified version of the Intervention Complexity Assessment Tool for Systematic Reviews (iCAT_SR), adapted to homeopathy-relevant dimensions, including the degree of individualization, consultation characteristics, and integration with co-interventions [26]. Two reviewers (DW, ML) independently coded eligible studies according to these dimensions, with disagreements resolved by consensus. The resulting profiles were summarized descriptively. Statistical analysis Data synthesis was guided by the Intervention Synthesis Questions (InSynQ) framework [27]. The corresponding checklist and synthesis plan are provided in supp. 6. Mean differences (MDs) were reported in their natural scale direction to preserve the interpretability of the original instruments (e.g., higher scores indicating worse outcomes). When necessary to synthesize outcomes across different scales, standardized mean differences (SMDs) were computed using Hedges’ g, following the standard formula where J is the small-sample correction factor and s p is the pooled standard deviation [28]. Effect directions were standardized such that positive values (>0) reflect a beneficial intervention effect. If multiple time points were reported, data from the longest follow-up were extracted. Missing standard deviations for change-from-baseline values were imputed according to the Cochrane Handbook (Section 6.5.2.8) [20], assuming a correlation coefficient of 0.5 as recommended by Fu et al. [29]. When required information was not directly reported, additional statistics were derived where possible from other reported information (e.g., confidence intervals, p-values, test statistics) following [13]. Where necessary, effect estimates were aligned to a consistent direction across studies; odds ratios were converted to standardized mean differences using the method described by [21] (see supp 4 ). Sensitivity analyses were conducted where approximations were necessary. For symptomatic outcomes, RCTs and NRSIs were synthesized separately. HP was compared independently against placebo and active controls. Analyses were also stratified by age group, with adults and children analysed separately. For adverse events, RCTs and NRSIs were analysed together using a narrative approach. We conducted random-effects meta-analyses using the Paule-Mandel estimator for between-study variance τ2 [31], with confidence intervals calculated using the Knapp-Hartung adjustment (KNHA) [32]. Between-study heterogeneity was evaluated using Cochrane’s Q test and quantified with the I² statistic [33] as well as a prediction interval [34]. According to commonly used benchmarks, I² values in the range of 30–60% suggest moderate heterogeneity, 50–90% indicate substantial heterogeneity, and 75–100% reflect considerable heterogeneity [35]. As an exploratory analysis, we calculated the overall symptom reduction to estimate the effect of HPs on insomnia across different studies with varying outcomes. To account for potential dependencies among effect sizes originating from the same study, we employed a multilevel meta-analytic approach. This model considers sampling variance at the level of individual effects (level 1), variance within studies (level 2), and variance between studies (level 3) [31, 36-38]. The analysis was conducted using the rma.mv function from the metafor package in R, assuming an intra-study correlation (rho) of 0.5 and incorporating the HKNA for aggregated data [39]. To test for possible publication bias, we visually controlled for funnel plot asymmetry, but did not conduct statistical tests due to the low number of studies [40]. Sensitivity analyses We conducted sensitivity analyses to assess the robustness of our findings and to examine the impact of alternative assumptions or methods: Sleep Quality: We included the within-subject crossover study by Bell et al. (2011). Total Sleep Duration: We assessed the effect of (a) excluding studies with data imputations as specified in supp. 4.1 , (b) including the Bell et al. (2011) study, and (c) including only studies with low or moderate risk of bias. Overall Symptom Reduction: We examined the impact of varying the intracluster correlation coefficient (rho), comparing values of rho=0, rho=0.5, and rho=0.9. Certainty of evidence We assessed the certainty of evidence using the GRADE approach [41] and rated the certainty in a non-null effect. Ratings of certainty started from “high certainty” for both RCTs and NRSIs, as the later were assessed with ROBINS-I [42], and included consideration of risk of bias, inconsistency, indirectness, imprecision, and publication bias. GRADE was assessed by two reviewers (DS, ML) with evidence synthesis background, checked by a reviewer with a medical background (AD) and also checked by a GRADE expert (LY, see acknowledgement). Software The meta-analyses were conducted using R 4.3.3 [43] and the packages metafor 4.8-0, meta 7.0-0, and bayesmeta 3.4.. Patient and Public Involvement Patient and public involvement (PPI) was incorporated to improve the accessibility and relevance of the Plain Language Summary (PLS) accompanying this systematic review. Following guideline from the Cochrane Consumer Network and GRIPP2, a draft PLS was shared with nine stakeholders, including six individuals with lived experience of insomnia, three public and/or health-system stakeholders experienced in reviewing patient information materials. Participants provided feedback on clarity, terminology, interpretation of findings, and relevance for patients. Feedback was thematically analyzed, and revisions were made to enhance accessibility while preserving accuracy of the evidence synthesis. RESULTS Literature Search and Study Selection The database search identified 1,143 records. After removing 263 duplicates and one retracted article, 876 records were excluded during title and abstract screening. Following full-text screening of 22 reports, 16 reports pertaining to 12 independent studies were included; in two cases, the same study was reported in both a doctoral dissertation and a journal article. The study selection process is detailed in the PRISMA flow diagram ( Figure 1 ). During full-text screening, six studies were excluded; four due to heterogeneous, non–insomnia-specific study populations. Study Characteristics Study characteristics are presented in in detail in supp. 7 . Eight RCTs [44-51] and four NRSIs [52-55] met the eligibility criteria. Study populations comprised adults and children with insomnia disorder as the primary condition under investigation, with sample sizes ranging from 28 to 320 subjects; diagnostic criteria were not applied uniformly across studies. The studies comprised journal articles [44, 45, 47, 49-52, 54, 55], conference abstracts or proceedings [46, 53], and a thesis [48]. Study durations ranged from four weeks ([45-48, 50, 52, 55], 6 weeks [51], 3 months [44, 49, 53] to follow-up periods of up to six months [54]. Interventions included individualized homeopathic treatment [44, 49-51, 54], specific single remedies such as Nux vomica or Coffea cruda [46, 48, 52], and complex homeopathic preparations [45, 47, 53, 55]. Comparators comprised placebo controls in most randomized trials [44, 45, 48-51] as well as active or usual-care controls in RCTs [46, 47] and non-randomized studies [53-55]. Outcomes varied substantially across studies, covering multiple domains of sleep architecture, insomnia severity, daytime functioning, psychological symptoms, and patient-reported outcomes. Risk of bias Risk of bias was assessed separately for each outcome and is reported alongside the corresponding meta-analyses ( supp. 8 ). Differences in risk of bias across outcomes within individual studies were rare. Michael et al. was the only RCT rated at low risk of bias across all assessed outcomes. Three of four NRSIs were judged to have a serious [55] or critical risk of bias [53, 54], which led to the exclusion of the two studies with critical risk of bias from the analysis of the total sleep duration (see fig. 2d, supp. 12). The predominant sources of bias were residual confounding due to inadequate adjustment, selection bias, and serious bias in outcome measurement. One RCT [44] and one NRSI [52] were assessed using the risk-of-bias instrument for cross-over RCTs (see fig. 2c, supp. 8 ). Intervention-specific assessments Model validity, assessing the degree to which the intervention reflects adequate homeopathic practice, was acceptable in four of the RCTs [48-51], indicating that the intervention was sufficiently representative of standard homeopathic practice. The validity of the four remaining RCTs was classified as uncertain, largely due to insufficient reporting regarding the rationale (Domain I) or principles (Domain II) of the therapy. The position of the studies on the efficacy–effectiveness continuum was assessed using the RITES tool, revealing considerable heterogeneity in trial design and real-world applicability. The mean of the domain-specific average scores of the eight RCTs on the RITES scale (1 = efficacy-oriented, 5 = effectiveness-oriented) was m = 2.25 (range: 1.25–4). The details of MVHT and RITES assessment scores are provided in s upp. 9. The NRSIs were assessed with the instruments on an exploratory basis only. Intervention complexity assessed with iCAT_SR varied across the studies (8 RCTs, 2 NRSIs). Half of the studies assessed single-component interventions (50%). Tailoring was most often complex or fully individualized (30% each). Practitioner skill, component interaction, and dependence on recipient or provider factors showed bimodal distributions, with equal proportions at low and high levels. The details of iCAT assessment are shown in s upp. 10 . Effects of Intervention Homeopathy vs. Placebo in Adults An overview of the results is presented in Table 1 and Certainty of Evidence is presented in Supp. 11. Table-1: Homeopathy vs. Placebo in Adults for Sleep-related Outcomes in Adults Outcome Moderator Scales Studies MD 95% CI I 2 Figure in supp. 8 quality of sleep - Pittsburgh Sleep Quality Index 1 -2.62 points -5.5 0.26 1a inclusion of non-randomized study (Bell 2011) Pittsburgh Sleep Quality Index 2 -0.99 points -3.21 1.23 61% 9 total sleep duration - Sleep diary 3 0.65 hours -0.9 2.2 77% 2a excluding studies with imputed data (Harrison 2013; Kolia-Adams 2010); =only study with low risk of bias Sleep diary 1 0.7 hours 0.42 0.98 10 inclusion of non-randomized study (Bell 2011) Sleep diary, in-home ambulatory polysomnography 4 0.77 hours -0.13 1.68 76% 11 studies with low/moderate risk of bias Sleep diary 2 0.4 hours -0.24 1.05 80% 12 insomnia severity - Insomnia severity index 1 -3.2 points -5.68 -0.72 3a sleep onset latency - Sleep diary 1 5.6 minutes -15.35 4.15 4a sleep efficiency - Sleep diary 1 6.9 points 3.99 9.86 5a Sleep Quality : Sleep quality was informed by a single RCT (n=30) [51]; the certainty of evidence for this outcome was rated as low. In the primary analysis, individualized homeopathy did not significantly improve sleep quality compared with placebo (MD=-2.62, 95% CI -5.50 to 0.26) [ fig. 1a/b, supp. 8 ] which was supported in sensitivity analysis when including a within subject crossover NRSI [ fig. 9, supp. 8 ]. Total Sleep Duration : Three RCTs [45, 48, 49], comprising a total of 124 participants, assessed total sleep duration (hours) using sleep diaries. The primary meta-analysis demonstrated no statistically significant difference between homeopathy and placebo (MD = 0.65; 95% CI −0.9 to 2.2), [ Fig. 2a/b, supp. 8 ]. The certainty of evidence was rated as low. Sensitivity analyses yielded consistent findings (see tab. 1). Naudé et al. (2010) reported between-group differences in sleep diary–based sleep duration but were excluded from the quantitative synthesis due to unavailable variance estimates (see supp. 4 ). Insomnia Severity : One RCT involving 60 participants assessed the Insomnia Severity Index and was included in the quantitative synthesis (MD = −3.2; 95% CI −5.7 to −0.7) [Fig. 3a/b; supp. 10]. The certainty of evidence was rated as moderate. Naudé et al. (2010) also assessed insomnia severity using the Sleep Impairment Index and reported between-group differences. Sleep onset latency and sleep efficiency. One RCT [49]; n=60), judged at low risk of bias, assessed both outcomes. Homeopathy was associated with an MD=−5.60 minutes (95% CI −15.35 to 4.15; low certainty) in sleep onset latency and a improvement in sleep efficiency (MD = 6.90; 95% CI 3.99 to 9.81; moderate certainty) compared with placebo [Figs. 4a/b and 5a/b; supp. 8]. Adverse Events : Only 2 of the 9 studies reported on adverse events [49, 55], [see tab. S12.1, supp. 8]. In Michael et al. (3-month intervention), one mild case of rectal bleeding occurred and was managed with homeopathic treatment; no serious AEs were reported [49] [see Fig. 7a, supp. 8 for risk of bias]. In one NRSI (4-week intervention), a single case of mild caffeine intolerance was observed [Fig. 7b, supp. 8 for risk of bias]. Both studies explicitly monitored AEs and reported high tolerability [55]. The remaining studies either did not monitor or did not report AEs, limiting the ability to estimate AE frequency reliably. This outcome is assessed to have low certainty of evidence. In an exploratory analysis, multiple sleep-related outcomes (total sleep time, insomnia severity, sleep-onset latency, sleep efficiency, and sleep quality) from five studies [45, 48, 49, 51] were pooled, yielding an SMD of 0.73 (95% CI [0.04, 1.41]). [Fig. 8 and fig. 13a-c, supp. 8]. Homeopathy vs. Placebo in Children Insomnia Severity: Evidence for this outcome was derived from a single open-label randomized trial in children (n=176) [47]. The certainty of evidence was rated as very low. The study reported a large effect favoring homeopathy over the active comparator (glycine) in reducing insomnia severity (SMD: 0.82, 95% CI 0.56 to 1.09) [Fig. 6a/b, supp. 8] which corresponds to a reported odds ratio of 4.45 (95% CI 2.77 to 7.14). Adverse Events: In the same trial involving 179 children under 6 years with sleep disorders [47], adverse events were systematically monitored (low certainty of evidence). Eleven non-serious adverse events were reported (six in the homeopathy group and five in the comparator group), most of which were considered unrelated to treatment. One child in the homeopathy group discontinued due to excitability. No serious adverse events were observed [see Fig. 7c, supp. 8 for risk of bias]. Reporting Biases The risk of bias due to missing results was assessed by visual inspection of funnel plots, however, given the small number of studies, funnel plots provide limited information and cannot be reliably interpreted, so no firm conclusions can be drawn. Formal tests for funnel plot asymmetry were not performed due to the small number of studies [Fig. 14-15, supp. 8]. Certainty of the Evidence For adults, evidence for adverse events, sleep quality, total sleep duration, and sleep onset latency was rated as low certainty, primarily due to high risk of bias (missing data, inadequate analyses) and imprecision (see supp. 11). Evidence for insomnia severity and sleep efficiency reached moderate certainty. For children, evidence for insomnia severity was of very low certainty and limited to a single open-label, industry-funded trial using a non-validated, proxy-reported measure. Evidence for adverse events in children was of low certainty (see supp. 12). Impact of Patient and Public Involvement Patient and public reviewers primarily suggested improvements to clarity and presentation. Explanatory phrases were added for methodological terms such as randomized and non-randomized studies, and a brief neutral description of homeopathy was included. Reviewers also recommended presenting the review’s main message earlier, acknowledging patient experiences of insomnia, and clarifying that different types of homeopathic interventions were evaluated. The section on adverse events was slightly expanded to emphasise safety considerations, and the glossary was referenced earlier in the text to improve navigation. The final version of the Plain Language Summary is presented at supp. 13. DISCUSSION Summary of Findings This systematic review assessed the evidence regarding the efficacy, effectiveness, and safety of homeopathic interventions for insomnia. Overall, the available evidence did not provide clear or consistent evidence of robust effects and was associated with uncertainty, driven by small sample sizes, high risk of bias and heterogeneity in study designs, reporting, patient populations, interventions, and outcomes. Notably, several trials were judged to reflect adequate homeopathic practice and covered a broad range along the efficacy-effectiveness continuum, indicating substantial heterogeneity in intervention complexity and real-world applicability. In adults, placebo-controlled evidence was inconclusive with respect to consistent benefits of homeopathy for core sleep outcomes. Signals of potential improvement in sleep duration emerged but were not statistically significant. Evidence for insomnia severity and other sleep parameters was limited to single studies, yielding low to moderate certainty. In children, evidence was restricted to one open-label RCT reporting large improvements compared with an active comparator; however, very low certainty of evidence and important design limitations preclude firm conclusions. Reporting of adverse events was sparse across studies, precluding firm conclusions regarding safety. Although the reported data did not indicate major tolerability concerns, the certainty of evidence regarding adverse events was rated as low to very low. Interpretation in the context of other evidence Taken together, our findings do not contradict earlier systematic reviews, which described the evidence for homeopathic interventions in insomnia as limited and inconclusive [10, 11]. Although the magnitude observed in our exploratory, non–outcome-specific analysis appears comparable to the large effects reported in a recent preprint pooling sleep outcomes [56], this estimate is substantially driven by a single study contributing multiple outcomes and around 50% of the meta-analytic weight. Any alignment between findings should therefore be considered tentative. While a complex systems perspective would predict effects across multiple outcomes rather than a single primary endpoint, the current evidence is insufficient to draw such inferences. Adverse events were infrequent and non-serious, consistent with findings from observational studies [57]. In that review, however, adverse events were systematically monitored and comprehensively reported in most included studies. By contrast, only a minority of trials in the present analysis reported active monitoring of adverse events. Due to a likely absence of reporting, estimates of adverse event frequency remain imprecise. Our assessment of the certainty of evidence was anchored to the null threshold, focusing on the presence of a relative effect rather than its magnitude, in line with established conceptual guidance [41] and considerations for complex interventions [58]. In parallel, and consistent with recent GRADE guidance [59], we examined whether observed point estimates were smaller than the smallest plausible minimal important differences (MIDs) to evaluate whether a target of little or no effect would be more appropriate. For several outcomes, including total sleep time and sleep onset latency, the absence of established MID values precluded application of this approach. For sleep quality, the observed effect exceeded the proposed MID of 2.5 points [60] and the non-null target was retained. For insomnia severity, published thresholds are heterogeneous and population-specific, and include estimates derived from different instruments or patient populations [61, 62]. Given these limitations, no definitive MID-based target modification was applied. A MID for total sleep duration has recently been proposed [63]; however, its applicability to the present evidence base remains uncertain given the heterogeneity across studies. For sleep onset latency and sleep efficiency, interpretation was further constrained by the lack of established MID thresholds. Against this background, the effects observed for homeopathic interventions should be interpreted with caution. The available evidence is constrained by imprecision, heterogeneity, small study numbers, and limited adverse-event reporting, which together preclude firm conclusions regarding both effectiveness and safety. This pattern of findings aligns with current insomnia guidelines, which consistently recommend cognitive behavioral therapy for insomnia (CBT-I) as first-line treatment, while reserving pharmacological therapies for selected patients and typically for short-term use [64, 65]. The preferential position of CBT-I in clinical guidelines is supported by a large and coherent body of evidence demonstrating clinically meaningful and durable improvements in insomnia severity and key sleep parameters [66]. Pharmacological treatments, by contrast, may offer short-term benefits, as shown in network meta-analyses, but require careful benefit–risk assessment [67]; concerns are particularly pronounced for Z-drugs in older adults, where associations with falls and fractures have been reported [68]. More broadly, the adverse-effect burden of pharmacological insomnia treatments is a clinically relevant reason to prioritize non-pharmacological strategies whenever feasible. At the same time, CBT-I remains underutilized in routine care due to barriers in access, availability, and implementation [69]. In this context, patient interest in low-threshold and perceived low-risk complementary approaches remains understandable, particularly where patients wish to avoid or minimize exposure to pharmacological treatment [70-72]. However, the current evidence does not allow homeopathy to be positioned as an evidence-based alternative or adjunct in insomnia care. Interpreting the findings of this review through a complexity-informed lens provides additional context for understanding the pronounced heterogeneity observed across studies. Homeopathy, as examined in the included trials, does not constitute a single, uniform intervention but rather encompasses approaches that differ with respect to treatment individualization, prescribing strategies, and trial design. A modified iCAT was applied with the aim of supporting a more structured reflection on intervention complexity within the evidence base [73]; however, limited reporting in the primary studies rarely allowed a differentiated assessment across multiple dimensions. Consequently, its application was largely restricted to a high-level characterization, most notably with respect to treatment individualization, illustrating the challenges of operationalizing complexity-oriented frameworks when key contextual and process-related information is insufficiently reported. Complementary assessments of model validity and trial pragmatism further highlighted the heterogeneity of the evidence base. According to the MVHT assessment, fewer than half of the included studies demonstrated acceptable concordance with contemporary homeopathic practice, while the RITES tool indicated a broad spectrum of designs ranging from more explanatory trials to studies with more pragmatic features. Together, these findings indicate that variability in intervention characteristics and study design is a key source of uncertainty in effect estimation and interpretation. Strengths and Limitations of the Evidence The results of this review should be interpreted in light of general limitations of the available evidence base. The included studies were predominantly small, frequently exhibited an elevated risk of bias, and showed substantial heterogeneity, including variability in reported outcomes. Several studies were identified as grey literature and demonstrated shortcomings in reporting quality. Only three studies defined their populations according to diagnostic reference standards (Riemann et al., 2022). The broad inclusion strategy of this review, which encompassed all prospective homeopathy RCTs and NRSIs in insomnia disorder, reflects the characteristics of the existing research field but also entails considerable clinical heterogeneity. This is particularly relevant given the joint consideration of individualized homeopathy and complex preparations and may have contributed to the observed statistical heterogeneity. Even if diagnostic procedures had been more consistently reported, the small number of available studies precluded moderator analyses to assess the influence of these or other factors on effect estimates. Another limitation is that effectiveness under routine care conditions could not be determined due to the lack of reliable NRSIs. Two of the four identified NRSIs were judged to be at critical risk of bias and were therefore excluded from further analyses. The remaining NRSIs either had a serious risk of bias or a cross-sectional design, which does not allow conclusions regarding real-world effectiveness. In addition, it was not possible to analyze global measures of symptom improvement or patient satisfaction based on the reported data, outcomes that are of particular relevance for holistic medical approaches such as homeopathy. The exploratory analysis intended to approximate overall symptom reduction by pooling different outcomes is limited, as it combines different constructs and measurement scales [74] and, in this review, is driven to a substantial extent by a single pilot study. The evidence was further limited by methodological weaknesses in most trials, restricted safety reporting, and scarcity of pediatric data, all of which reduce confidence in the estimates and limit generalizability. One strength of this review is the comprehensive literature search and non-restrictive inclusion criteria, which reduced the risk of missing relevant studies, including those not published in peer-reviewed journals. All stages of the review were conducted independently by two reviewers. Domain experts were involved in the MVHT and RITES assessments as well as in the clinical evaluation. Patients were involved in the development of both the protocol and the manuscript, and patient perspectives were considered in relation to clinical relevance. Although the protocol initially prioritized the CATHIS tool, insufficient inter-rater reliability identified in a parallel validation study [75] necessitated an adapted methodological approach. The use of MVHT and RITES instead allowed a more reliable characterization of intervention fidelity and trial pragmatism based on the available reporting. Finally, PPI improved the accessibility of the review outputs by identifying areas where technical language could limit understanding for non-specialist readers. Feedback also highlighted the importance of clearly communicating uncertainty and safety, which are key concerns for patients considering complementary treatments. Although PPI focused on improving knowledge translation rather than influencing analytical stages of the review, it helped produce a clearer and more accessible summary of the evidence. Implications and conclusions Overall, the available evidence for homeopathic treatments for insomnia is limited, and the effects remain uncertain, with no reliable evidence demonstrating a specific therapeutic effect. The existing literature is dominated by small and exploratory studies, many of which exhibit limitations in design and reporting. These shortcomings align with previously documented challenges in internal, external, and model validity within homeopathic clinical research, some of which may be attributable to incomplete or inconsistent reporting rather than study conduct per se [76]. From a clinical perspective, the current evidence does not provide consistent or high-certainty support for the use of homeopathy as a treatment for insomnia or general sleep disturbances in adults. While certain analyses, particularly for insomnia severity and sleep efficiency, suggest potential benefits, these signals are sensitive to methodological decisions, heterogeneity, and the inclusion of lower-quality studies. Clinicians should therefore exercise caution when considering homeopathy for insomnia and prioritize evidence-based interventions with stronger and more reliable therapeutic profiles. In paediatric populations, where only one open-label trial was available, the very low certainty of evidence and methodological limitations preclude us from providing any clinical recommendation. In this context, additional small or methodologically limited studies are unlikely to substantially advance the evidence base and may continue to contribute only marginally to knowledge accumulation. Future research efforts should therefore focus on a rigorously designed, independently conducted confirmatory replication based on the protocol of Michael et al., which currently represents the only study within the evidence base demonstrating both low risk of bias and acceptable homeopathic model validity. Such a trial should be prospectively registered, strictly adhere to CONSORT reporting standards, and ensure full transparency and reproducibility. In addition to placebo-controlled designs, future studies may also consider comparative effectiveness designs evaluating the incremental benefit of homeopathic treatment as an adjunct to established standard care, such as cognitive behavioral therapy for insomnia. In line with contemporary frameworks for evidence synthesis of complex and whole medical systems, which emphasize the role of context and complexity, future trials should also systematically capture and report relevant contextual factors, including consultation characteristics, patient expectations and prior experiences with homeopathy, as well as global and patient-reported outcomes such as overall satisfaction [12]. These elements are essential for the adequate evaluation and interpretation of homeopathy as a complex intervention. In addition, trials must incorporate active and systematic surveillance for adverse events to allow a robust assessment of safety. From a policy and research governance perspective, these findings support greater methodological standardization, including core outcome sets, trial preregistration, and transparent safety reporting. At the same time, given the current uncertainty of the evidence, policy decisions regarding the inclusion or exclusion of homeopathy-based interventions for insomnia in public health programs or insurance coverage would benefit from a cautious and proportionate approach. Any future investment in this field should prioritize well-powered, placebo-controlled trials with standardized outcomes and comprehensive adverse-event reporting. Accordingly, in the absence of reproducible evidence meeting these methodological and reporting standards, the specific therapeutic value of homeopathy for insomnia remains uncertain. Declarations Registration and protocol The protocol was registered under Prospero with the number CRD420251015627. Protocol amendments The protocol did not specify how insomnia should be operationalized during study selection. Prior to data extraction and analysis, we clarified the population definition by operationalizing insomnia as a primary diagnosis. This was done to distinguish insomnia as the condition under investigation from studies assessing sleep outcomes secondary to other primary conditions. This clarification did not alter the set of included studies. The DART-Europe e-theses portal, originally planned as a search source, was permanently closed on 3 February 2025. As an alternative, we searched Google Scholar using the search terms "homeopathy insomnia" and screened the first 100 results, sorted by relevance. Because a validation study conducted in parallel with the systematic review revealed low interrater reliability of the CATHIS core [75], the instrument was replaced by MVHT and RITES for assessing model validity and clinical relevance; the corresponding methods and results are provided in the project’s online repository. Acknowledgement We thank Prof. Ashley Hilton Adrian Ross (Durban university of technology, South Africa) for providing raw material of the Naudé publications, Prof. Liang Yao (Nanyang Technological University, Singapore) for support in assessing GRADE, Dr. Subhranil Saha (D N De Homoeopathic Medical College and Hospital, Kolkata, Govt. of West Bengal. India) for participating in the CATHIS core assessment, and Dr. Hebatullah Mohamed Abdulazeem (Technical University of Munich, Germany) for helpful comments. Support This study was supported by the Software AG Stiftung, Darmstadt, Germany. SK has been financed by the Ursimone Wietlisbach Foundation. Declaration of generative AI and AI-assisted technologies in the writing process Artificial intelligence tools were accessed via web interface to draft a plain language summary, to refine the language and structure of the manuscript, and to support R code debugging and optimization. OpenAI ChatGPT (version 5.2; February 2026) generated an initial draft of the plain language summary which was revised by the authors. A GPT-5 series ChatGPT model (November 2025–March 2026) was used for language editing, restructuring for clarity, and consistency checks against cited literature within the manuscript. All AI-generated outputs were critically reviewed and verified by the authors, who retain full responsibility for the content, methods, and conclusions of the review. Conflict of interest DS, SK, PW, and ML declare that no competing financial interests exist. AD, DW, PW, KG work as homeopathic doctors. RvH provided consultancy services to Heel Biologische Heilmittel GmbH, a manufacturer of Homeopathic Preparations, and to the 'European Coalition on Homeopathic and Anthroposophic Medicinal Products' (ECHAMP), which is a European Economic Interest Grouping (EEIG) of companies active in the production and distribution of Homeopathic Products. 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Herman, P.M., et al., The current state of the quality of homeopathic clinical research. Complementary Therapies in Medicine, 2025. 88 : p. 103108. Additional Declarations No competing interests reported. Supplementary Files Supplement1.docx Supplement2.docx Supplement3.docx Supplement4.docx Supplement5.docx Supplement6.xlsx Supplement7.xlsx Supplement8RoBMA.docx Supplement9MVHTRITES.docx Supplement10iCAT.xlsx Supplement11.docx Supplement12.docx Supplement13PlainLanguageSummary.docx SupplementLegends.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Recent estimates suggest that insomnia affects 16.2% of adults globally, with 7.9% experiencing severe insomnia, and the highest burden observed among older adults, women, and individuals with comorbid medical or psychiatric conditions [4, 5]. Beyond individual suffering, chronic insomnia is increasingly recognized both as a clinical and a public health issue, contributing to impaired cognitive and physical functioning, increased risks for cardiovascular and metabolic diseases, reduced quality of life, and substantial societal costs including work absenteeism, productivity loss, and elevated healthcare utilization [4, 6, 7].\u003c/p\u003e\n\u003cp\u003eClinical management of insomnia remains challenging despite advances in understanding its pathophysiology and an expanding array of interventions. Pharmacologic therapies, notably benzodiazepine receptor agonists, are commonly prescribed but raise concerns about tolerance, dependence, residual sedation, and cognitive impairment with long-term use [5]. Cognitive behavioural therapy for insomnia (CBT-I) is recommended as the first-line treatment, but implementation is hampered by restricted access, patient adherence barriers, and gradual response times [8]. These limitations have spurred interest in alternative or complementary therapies that may offer safer, accessible, and effective options for those who are refractory to, or prefer, nonpharmacologic strategies.\u003c/p\u003e\n\u003cp\u003eHomeopathy, based on the principle of \u0026ldquo;treat likes by likes\u0026rdquo; and individualized use of highly diluted substances [9], is an alternative approach for insomnia treatment: The clinical evidence base remains inconsistent and subject to methodological criticism, such as small sample sizes, population heterogeneity, variable homeopathic preparations, and outcome measure inconsistency [10].\u003c/p\u003e\n\u003cp\u003eCurrent interest in integrating traditional, complementary and integrative medicine modalities into mainstream care, underscores the need for a rigorous, up-to-date evidence synthesis employing comprehensive search strategies and robust bias assessment tools. Earlier systematic reviews concluded that evidence for homeopathy in insomnia was unconvincing, but these reviews were conducted more than a decade ago and did not include quantitative synthesis or more recent trials and grey literature [10, 11]. Accordingly, this systematic review and outcome-specific meta-analysis updates and extends earlier syntheses to evaluate the efficacy, effectiveness and safety of homeopathic interventions for insomnia, adopting a complex systems perspective that incorporates patient involvement, model validity, and efficacy\u0026ndash;effectiveness considerations [12].\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eThis systematic review was conducted in accordance with the methodological guidance provided in the \u003cem\u003eCochrane Handbook for Systematic Reviews of Interventions\u003c/em\u003e [13]. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement [14], the PRISMA-S extension for literature searches [15], and the GRIPP2 guideline for patient involvement [16]. The review protocol was prospectively registered in the PROSPERO database (registration number: CRD420251015627) in combination with a template protocol [14]. The present review adopts the template protocol in full [17], with insomnia-specific adaptations (see \u003cstrong\u003esupp. 1\u003c/strong\u003e).\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eLiterature search and study selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn February, 21st, 2025 (last update by rerunning all searches: 13.8.2025), we conducted a systematic literature search according to chapter 4 of the Cochrane Handbook of Systematic Reviews [18] and the PRESS peer review guideline [19]; one experienced reviewer (ML) and an information specialist (SK) were involved in the process. We searched databases (the HOMIS database [20], MEDLINE, EMBASE, CINAHL, LILACS, AMED, PsycInfo, Cochrane Library, Web of Science) from the beginning of the databases until February 20th, trial registries (clinicaltrials.gov, trialsearch.who.int, clinicaltrialsregister.eu), preprint servers (OSF, medRxiv), ProQuest Dissertations \u0026amp; Theses Citation Index and oatd.org for theses, as well as the Indian Ministry of AYUSH research portal (ayushportal.nic.in, google scholar). The search strategy combined terms regarding homeopathy, study design (randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs), and insomnia, without language or search filter restrictions. The search strategy was developed by one reviewer (ML) and checked by an information specialist (SK). Details of the search strategy are documented in \u003cstrong\u003esupp. 2.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResults from the literature searches were exported to Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia (available at www.covidence.org). After removal of duplicates, two reviewers (ML, SK) independently assessed study eligibility. Differences of opinion were resolved through discussion.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eEligibility criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudies were eligible if they were prospective, comparative, and evaluated the efficacy, effectiveness, or safety of homeopathic preparations (HPs) in individuals with insomnia disorder. We included randomized controlled trials (RCTs) and prospective non-randomized studies of interventions (NRSIs) to capture both experimental and real-world evidence.\u003c/p\u003e\n\u003cp\u003eParticipants had insomnia as the condition under investigation. For study selection, insomnia was operationalized as a primary diagnosis of insomnia disorder, as reported by the study authors. This operationalization was used to distinguish studies in which insomnia was the index condition from populations treated for other primary conditions in which sleep or sleep quality was assessed only as a secondary outcome. All exclusions were documented.\u003c/p\u003e\n\u003cp\u003eInterventions comprised any HP prepared in accordance with a nationally recognized homeopathic pharmacopoeia, administered by any route (e.g., oral, sublingual, topical). Both individualized (classical) and non-individualized homeopathy were eligible. Co-interventions were permitted if the comparator group received an identical regimen excluding the HMP, ensuring the specific effect of homeopathy could be isolated.\u003c/p\u003e\n\u003cp\u003eComparator arms included inactive controls (e.g., placebo, no treatment, waiting list) and active comparators (e.g., pharmacological agents, psychological therapies, or physical interventions). Studies were required to assess at least one clinical outcome at a minimum of two time points (pre- and post-intervention). Studies reporting only economic outcomes were excluded.\u003c/p\u003e\n\u003cp\u003eWe excluded retrospective designs, cross-sectional studies, uncontrolled before\u0026ndash;after studies, interrupted time series, case series, case reports, and any study subject to retraction or formal expression of concern. A detailed summary of the inclusion and exclusion criteria is provided in \u003cstrong\u003esupp. 3.\u003c/strong\u003e No language restrictions or other limitations were applied. Details of studies excluded after full-text screening, including reasons for exclusion, are provided in \u003cstrong\u003esupp. 4\u003c/strong\u003e, \u003cstrong\u003etable S.3.\u003c/strong\u003e \u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eData-extraction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo reviewers (ML, DS) independently extracted data into Covidence using a structured codebook, describing the extracted variables. Variables included publication details (country, year), study design, participant demographics (mean age, gender, sample size, dropouts), intervention characteristics (type of homeopathy, potency, frequency), comparator type, duration of intervention, primary and secondary outcomes, effect size estimates, and funding sources. Discrepancies between reviewers were resolved through discussion. The codebook is provided in \u003cstrong\u003esupp. 5.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor each study, pre\u0026ndash;post mean differences and their corresponding standard deviations were extracted for treatment and control groups and analysed as outcome measures. Further details on author contact are provided in \u003cstrong\u003eSupp. 4\u003c/strong\u003e.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eRisk of bias\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo assess the risk of bias, the Cochrane risk-of-bias tool for randomized trials (RoB 2) was used for RCTs and its supplement for crossover trials [22] and Cochrane\u0026rsquo;s ROBINS-I V2 for NRSIs [23]. Assessments followed the standard domains and decision algorithms as specified in the respective tools. Studies were evaluated on an outcome-specific basis by two reviewers independently (ML, DS), and disagreements were resolved through discussion.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFurther assessments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eModel validity of RCTs was assessed using the MVHT instrument (overall judgement: inadequate, uncertain, acceptable) [24]. Two experienced physicians and homeopaths (AD, DW) rated all studies independently; disagreements were resolved by discussion mediated by a third reviewer (ML). To position trials on the efficacy\u0026ndash;effectiveness continuum, we applied the RITES tool (scale from 1 to 5, with 1 = strong emphasis on efficacy and 5 = strong emphasis on effectiveness) [25]. The same reviewers (AD, DW) performed independent ratings; disagreements were resolved by discussion mediated by a third reviewer (ML). We applied a modified version of the Intervention Complexity Assessment Tool for Systematic Reviews (iCAT_SR), adapted to homeopathy-relevant dimensions, including the degree of individualization, consultation characteristics, and integration with co-interventions [26]. Two reviewers (DW, ML) independently coded eligible studies according to these dimensions, with disagreements resolved by consensus. The resulting profiles were summarized descriptively. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData synthesis was guided by the Intervention Synthesis Questions (InSynQ) framework [27]. The corresponding checklist and synthesis plan are provided in \u003cstrong\u003esupp. 6.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMean differences (MDs) were reported in their natural scale direction to preserve the interpretability of the original instruments (e.g., higher scores indicating worse outcomes). When necessary to synthesize outcomes across different scales, standardized mean differences (SMDs) were computed using Hedges\u0026rsquo; g, following the standard formula \u003cv:shapetype id=\"_x0000_t75\" coordsize=\"21600,21600\" o:spt=\"75\" o:preferrelative=\"t\" path=\"m@4@5l@4@11@9@11@9@5xe\" filled=\"f\" stroked=\"f\"\u003e \u003cv:stroke joinstyle=\"miter\"\u003e \u003cv:formulas\u003e \u003cv:f eqn=\"if lineDrawn pixelLineWidth 0\"\u003e \u003cv:f eqn=\"sum @0 1 0\"\u003e \u003cv:f eqn=\"sum 0 0 @1\"\u003e \u003cv:f eqn=\"prod @2 1 2\"\u003e \u003cv:f eqn=\"prod @3 21600 pixelWidth\"\u003e \u003cv:f eqn=\"prod @3 21600 pixelHeight\"\u003e \u003cv:f eqn=\"sum @0 0 1\"\u003e \u003cv:f eqn=\"prod @6 1 2\"\u003e \u003cv:f eqn=\"prod @7 21600 pixelWidth\"\u003e \u003cv:f eqn=\"sum @8 21600 0\"\u003e \u003cv:f eqn=\"prod @7 21600 pixelHeight\"\u003e \u003cv:f eqn=\"sum @10 21600 0\"\u003e \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:f\u003e\n \u003c/v:formulas\u003e\n \u003cv:path o:extrusionok=\"f\" gradientshapeok=\"t\" o:connecttype=\"rect\"\u003e \u003c/v:path\u003e\n \u003c/v:stroke\u003e\n \u003c/v:shapetype\u003e\n \u003cv:shape id=\"_x0000_i1025\" type=\"#_x0000_t75\"\u003e \u003cv:imagedata src=\"file:///C%3A/Users/btr8097/AppData/Local/Packages/oice_16_974fa576_32c1d314_38e4/AC/Temp/msohtmlclip1/01/clip_image001.png\" o:title=\"\" chromakey=\"white\"\u003e \u003c/v:imagedata\u003e\n \u003c/v:shape\u003e\n\u003c/p\u003e\n\u003cp\u003ewhere J is the small-sample correction factor and s\u003csub\u003ep\u003c/sub\u003e is the pooled standard deviation [28]. Effect directions were standardized such that positive values (\u0026gt;0) reflect a beneficial intervention effect. \u003c/p\u003e\n\u003cp\u003eIf multiple time points were reported, data from the longest follow-up were extracted. Missing standard deviations for change-from-baseline values were imputed according to the Cochrane Handbook (Section 6.5.2.8) [20], assuming a correlation coefficient of 0.5 as recommended by Fu et al. [29]. When required information was not directly reported, additional statistics were derived where possible from other reported information (e.g., confidence intervals, p-values, test statistics) following [13]. Where necessary, effect estimates were aligned to a consistent direction across studies; odds ratios were converted to standardized mean differences using the method described by [21] (see \u003cstrong\u003esupp 4\u003c/strong\u003e). Sensitivity analyses were conducted where approximations were necessary.\u003c/p\u003e\n\u003cp\u003eFor symptomatic outcomes, RCTs and NRSIs were synthesized separately. HP was compared independently against placebo and active controls. Analyses were also stratified by age group, with adults and children analysed separately. For adverse events, RCTs and NRSIs were analysed together using a narrative approach.\u003c/p\u003e\n\u003cp\u003eWe conducted random-effects meta-analyses using the Paule-Mandel estimator for between-study variance \u0026tau;2 [31], with confidence intervals calculated using the Knapp-Hartung adjustment (KNHA) [32]. Between-study heterogeneity was evaluated using Cochrane\u0026rsquo;s Q test and quantified with the I\u0026sup2; statistic [33] as well as a prediction interval [34]. According to commonly used benchmarks, I\u0026sup2; values in the range of 30\u0026ndash;60% suggest moderate heterogeneity, 50\u0026ndash;90% indicate substantial heterogeneity, and 75\u0026ndash;100% reflect considerable heterogeneity [35].\u003c/p\u003e\n\u003cp\u003eAs an exploratory analysis, we calculated the overall symptom reduction to estimate the effect of HPs on insomnia across different studies with varying outcomes. To account for potential dependencies among effect sizes originating from the same study, we employed a multilevel meta-analytic approach. This model considers sampling variance at the level of individual effects (level 1), variance within studies (level 2), and variance between studies (level 3) [31, 36-38]. The analysis was conducted using the rma.mv function from the metafor package in R, assuming an intra-study correlation (rho) of 0.5 and incorporating the HKNA for aggregated data [39]. \u003c/p\u003e\n\u003cp\u003eTo test for possible publication bias, we visually controlled for funnel plot asymmetry, but did not conduct statistical tests due to the low number of studies [40].\u003c/p\u003e\n\n\u003cp\u003e\u003cu\u003eSensitivity analyses\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted sensitivity analyses to assess the robustness of our findings and to examine the impact of alternative assumptions or methods: \u003c/p\u003e\n\u003cul class=\"decimal_type\"\u003e\n\u003cli\u003eSleep Quality: We included the within-subject crossover study by Bell et al. (2011).\u003c/li\u003e\n\u003cli\u003eTotal Sleep Duration: We assessed the effect of (a) excluding studies with data imputations as specified in \u003cstrong\u003esupp. 4.1\u003c/strong\u003e, (b) including the Bell et al. (2011) study, and (c) including only studies with low or moderate risk of bias.\u003c/li\u003e\n\u003cli\u003eOverall Symptom Reduction: We examined the impact of varying the intracluster correlation coefficient (rho), comparing values of rho=0, rho=0.5, and rho=0.9.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cu\u003eCertainty of evidence\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eWe assessed the certainty of evidence using the GRADE approach [41] and rated the certainty in a non-null effect. Ratings of certainty started from \u0026ldquo;high certainty\u0026rdquo; for both RCTs and NRSIs, as the later were assessed with ROBINS-I [42], and included consideration of risk of bias, inconsistency, indirectness, imprecision, and publication bias. GRADE was assessed by two reviewers (DS, ML) with evidence synthesis background, checked by a reviewer with a medical background (AD) and also checked by a GRADE expert (LY, see acknowledgement).\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eSoftware\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe meta-analyses were conducted using R 4.3.3 [43] and the packages metafor 4.8-0, meta 7.0-0, and bayesmeta 3.4..\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePatient and Public Involvement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient and public involvement (PPI) was incorporated to improve the accessibility and relevance of the Plain Language Summary (PLS) accompanying this systematic review. Following guideline from the Cochrane Consumer Network and GRIPP2, a draft PLS was shared with nine stakeholders, including six individuals with lived experience of insomnia, three public and/or health-system stakeholders experienced in reviewing patient information materials. Participants provided feedback on clarity, terminology, interpretation of findings, and relevance for patients. Feedback was thematically analyzed, and revisions were made to enhance accessibility while preserving accuracy of the evidence synthesis.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003eLiterature Search and Study Selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe database search identified 1,143 records. After removing 263 duplicates and one retracted article, 876 records were excluded during title and abstract screening. Following full-text screening of 22 reports, 16 reports pertaining to 12 independent studies were included; in two cases, the same study was reported in both a doctoral dissertation and a journal article. The study selection process is detailed in the PRISMA flow diagram (\u003cstrong\u003eFigure 1\u003c/strong\u003e). During full-text screening, six studies were excluded; four due to heterogeneous, non\u0026ndash;insomnia-specific study populations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy characteristics are presented in in detail in \u003cstrong\u003esupp. 7\u003c/strong\u003e. Eight RCTs [44-51] and four NRSIs [52-55] met the eligibility criteria. Study populations comprised adults and children with insomnia disorder as the primary condition under investigation, with sample sizes ranging from 28 to 320 subjects; diagnostic criteria were not applied uniformly across studies. The studies comprised journal articles [44, 45, 47, 49-52, 54, 55], conference abstracts or proceedings [46, 53], and a thesis [48]. Study durations ranged from four weeks ([45-48, 50, 52, 55], 6 weeks [51], 3 months [44, 49, 53] to follow-up periods of up to six months [54]. Interventions included individualized homeopathic treatment [44, 49-51, 54], specific single remedies such as \u003cem\u003eNux vomica\u003c/em\u003e or \u003cem\u003eCoffea cruda\u003c/em\u003e [46, 48, 52], and complex homeopathic preparations [45, 47, 53, 55]. Comparators comprised placebo controls in most randomized trials [44, 45, 48-51] as well as active or usual-care controls in RCTs [46, 47] and non-randomized studies [53-55]. Outcomes varied substantially across studies, covering multiple domains of sleep architecture, insomnia severity, daytime functioning, psychological symptoms, and patient-reported outcomes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRisk of bias\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRisk of bias was assessed separately for each outcome and is reported alongside the corresponding meta-analyses (\u003cstrong\u003esupp. 8\u003c/strong\u003e). Differences in risk of bias across outcomes within individual studies were rare. Michael et al. was the only RCT rated at low risk of bias across all assessed outcomes. Three of four NRSIs were judged to have a serious [55] or critical risk of bias [53, 54], which led to the exclusion of the two studies with critical risk of bias from \u0026nbsp;the analysis of the total sleep duration (see fig. 2d, supp. 12). The predominant sources of bias were residual confounding due to inadequate adjustment, selection bias, and serious bias in outcome measurement. One RCT [44] and one NRSI [52] were assessed using the risk-of-bias instrument for cross-over RCTs (see \u003cstrong\u003efig. 2c, supp. 8\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention-specific assessments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eModel validity, assessing the degree to which the intervention reflects adequate homeopathic practice, was acceptable in four of the RCTs [48-51], indicating that the intervention was sufficiently representative of standard homeopathic practice. The validity of the four remaining RCTs was classified as uncertain, largely due to insufficient reporting regarding the rationale (Domain I) or principles (Domain II) of the therapy. The position of the studies on the efficacy\u0026ndash;effectiveness continuum was assessed using the RITES tool, revealing considerable heterogeneity in trial design and real-world applicability. The mean of the domain-specific average scores of the eight RCTs on the RITES scale (1 = efficacy-oriented, 5 = effectiveness-oriented) was m = 2.25 (range: 1.25\u0026ndash;4). The details of MVHT and RITES assessment scores are provided in \u003cstrong\u003es\u003c/strong\u003e\u003cstrong\u003eupp. 9.\u003c/strong\u003e The NRSIs were assessed with the instruments on an exploratory basis only.\u003c/p\u003e\n\u003cp\u003eIntervention complexity assessed with iCAT_SR varied across the studies (8 RCTs, 2 NRSIs). Half of the studies assessed single-component interventions (50%). Tailoring was most often complex or fully individualized (30% each). Practitioner skill, component interaction, and dependence on recipient or provider factors showed bimodal distributions, with equal proportions at low and high levels. The details of iCAT assessment are shown in \u003cstrong\u003es\u003c/strong\u003e\u003cstrong\u003eupp. 10\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffects of Intervention\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eHomeopathy vs. Placebo in Adults\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAn overview of the results is presented in \u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003eand Certainty of Evidence is presented in\u003cstrong\u003e\u0026nbsp;Supp. 11.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable-1: Homeopathy vs. Placebo in Adults for Sleep-related Outcomes in Adults\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width: 100%;border: none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eModerator\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eScales\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eStudies\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eI\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eFigure in supp. 8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" rowspan=\"2\"\u003e\n \u003cp\u003equality of sleep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePittsburgh Sleep Quality Index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e-2.62 points\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e-5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e1a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003einclusion of non-randomized study (Bell 2011)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePittsburgh Sleep Quality Index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e-0.99 points\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e-3.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e1.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e61%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" rowspan=\"4\"\u003e\n \u003cp\u003etotal sleep duration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSleep diary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e0.65 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e-0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e77%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e2a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eexcluding studies with imputed data (Harrison 2013; Kolia-Adams 2010); =only study with low risk of bias\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSleep diary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e0.7 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003einclusion of non-randomized study (Bell 2011)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSleep diary, in-home ambulatory polysomnography\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e0.77 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e-0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e1.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e76%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003estudies with low/moderate risk of bias\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSleep diary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e0.4 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e-0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e80%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003einsomnia severity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eInsomnia severity index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e-3.2 points\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e-5.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e-0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e3a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003esleep onset latency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSleep diary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e5.6 minutes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e-15.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e4.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e4a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003esleep efficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSleep diary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e6.9 points\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e3.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e9.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\"\u003e\n \u003cp\u003e5a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eSleep Quality\u003c/em\u003e: Sleep quality was informed by a single RCT (n=30) [51]; the certainty of evidence for this outcome was rated as low. In the primary analysis, individualized homeopathy did not significantly improve sleep quality compared with placebo (MD=-2.62, 95% CI -5.50 to 0.26) [\u003cstrong\u003efig. 1a/b, supp. 8\u003c/strong\u003e] which was supported in sensitivity analysis when including a within subject crossover NRSI [\u003cstrong\u003efig. 9, supp. 8\u003c/strong\u003e].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTotal Sleep Duration\u003c/em\u003e: Three RCTs [45, 48, 49], comprising a total of 124 participants, assessed total sleep duration (hours) using sleep diaries. The primary meta-analysis demonstrated no statistically significant difference between homeopathy and placebo (MD = 0.65; 95% CI \u0026minus;0.9 to 2.2), [\u003cstrong\u003eFig. 2a/b, supp. 8\u003c/strong\u003e]. The certainty of evidence was rated as low. Sensitivity analyses yielded consistent findings (see tab. 1). Naud\u0026eacute; et al. (2010) reported between-group differences in sleep diary\u0026ndash;based sleep duration but were excluded from the quantitative synthesis due to unavailable variance estimates (see \u003cstrong\u003esupp. 4\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eInsomnia Severity\u003c/em\u003e: One RCT involving 60 participants assessed the Insomnia Severity Index and was included in the quantitative synthesis (MD = \u0026minus;3.2; 95% CI \u0026minus;5.7 to \u0026minus;0.7) [Fig. 3a/b; supp. 10]. The certainty of evidence was rated as moderate. Naud\u0026eacute; et al. (2010) also assessed insomnia severity using the Sleep Impairment Index and reported between-group differences.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSleep onset latency and sleep efficiency.\u0026nbsp;\u003c/em\u003eOne RCT [49]; n=60), judged at low risk of bias, assessed both outcomes. Homeopathy was associated with an MD=\u0026minus;5.60 minutes (95% CI \u0026minus;15.35 to 4.15; low certainty) in sleep onset latency and a improvement in sleep efficiency (MD = 6.90; 95% CI 3.99 to 9.81; moderate certainty) compared with placebo [Figs. 4a/b and 5a/b; supp. 8].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAdverse Events\u003c/em\u003e: Only 2 of the 9 studies reported on adverse events [49, 55], [see tab. S12.1, supp. 8]. In Michael et al. (3-month intervention), one mild case of rectal bleeding occurred and was managed with homeopathic treatment; no serious AEs were reported [49] [see Fig. 7a, supp. 8 for risk of bias]. In one NRSI (4-week intervention), a single case of mild caffeine intolerance was observed [Fig. 7b, supp. 8 for risk of bias]. Both studies explicitly monitored AEs and reported high tolerability [55]. The remaining studies either did not monitor or did not report AEs, limiting the ability to estimate AE frequency reliably. This outcome is assessed to have low certainty of evidence.\u003c/p\u003e\n\u003cp\u003eIn an exploratory analysis, multiple sleep-related outcomes (total sleep time, insomnia severity, sleep-onset latency, sleep efficiency, and sleep quality) from five studies [45, 48, 49, 51] were pooled, yielding an SMD of 0.73 (95% CI [0.04, 1.41]). [Fig. 8 and fig. 13a-c, supp. 8].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eHomeopathy vs. Placebo in Children\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eInsomnia Severity:\u003c/em\u003e Evidence for this outcome was derived from a single open-label randomized trial in children (n=176) [47]. The certainty of evidence was rated as very low. The study reported a large effect favoring homeopathy over the active comparator (glycine) in reducing insomnia severity (SMD: 0.82, 95% CI 0.56 to 1.09) [Fig. 6a/b, supp. 8] which corresponds to a reported odds ratio of 4.45 (95% CI 2.77 to 7.14).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAdverse Events:\u0026nbsp;\u003c/em\u003eIn the same trial involving 179 children under 6 years with sleep disorders [47], adverse events were systematically monitored (low certainty of evidence). Eleven non-serious adverse events were reported (six in the homeopathy group and five in the comparator group), most of which were considered unrelated to treatment. One child in the homeopathy group discontinued due to excitability. No serious adverse events were observed [see Fig. 7c, supp. 8 for risk of bias].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReporting Biases\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe risk of bias due to missing results was assessed by visual inspection of funnel plots, however, given the small number of studies, funnel plots provide limited information and cannot be reliably interpreted, so no firm conclusions can be drawn. Formal tests for funnel plot asymmetry were not performed due to the small number of studies [Fig. 14-15,\u0026nbsp;supp. 8].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCertainty of the Evidence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor adults, evidence for adverse events, sleep quality, total sleep duration, and sleep onset latency was rated as low certainty, primarily due to high risk of bias (missing data, inadequate analyses) and imprecision (see supp. 11). Evidence for insomnia severity and sleep efficiency reached moderate certainty.\u003c/p\u003e\n\u003cp\u003eFor children, evidence for insomnia severity was of very low certainty and limited to a single open-label, industry-funded trial using a non-validated, proxy-reported measure. Evidence for adverse events in children was of low certainty (see supp. 12).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImpact of Patient and Public Involvement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient and public reviewers primarily suggested improvements to clarity and presentation. Explanatory phrases were added for methodological terms such as randomized and non-randomized studies, and a brief neutral description of homeopathy was included.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eReviewers also recommended presenting the review\u0026rsquo;s main message earlier, acknowledging patient experiences of insomnia, and clarifying that different types of homeopathic interventions were evaluated. The section on adverse events was slightly expanded to emphasise safety considerations, and the glossary was referenced earlier in the text to improve navigation. The final version of the Plain Language Summary is presented at \u003cstrong\u003esupp. 13.\u003c/strong\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003e\u003cstrong\u003eSummary of Findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis systematic review assessed the evidence regarding the efficacy, effectiveness, and safety of homeopathic interventions for insomnia. Overall, the available evidence did not provide clear or consistent evidence of robust effects and was associated with uncertainty, driven by small sample sizes, high risk of bias and heterogeneity in study designs, reporting, patient populations, interventions, and outcomes. Notably, several trials were judged to reflect adequate homeopathic practice and covered a broad range along the efficacy-effectiveness continuum, indicating substantial heterogeneity in intervention complexity and real-world applicability.\u003c/p\u003e\n\u003cp\u003eIn adults, placebo-controlled evidence was inconclusive with respect to consistent benefits of homeopathy for core sleep outcomes. Signals of potential improvement in sleep duration emerged but were not statistically significant. Evidence for insomnia severity and other sleep parameters was limited to single studies, yielding low to moderate certainty.\u003c/p\u003e\n\u003cp\u003eIn children, evidence was restricted to one open-label RCT reporting large improvements compared with an active comparator; however, very low certainty of evidence and important design limitations preclude firm conclusions.\u003c/p\u003e\n\u003cp\u003eReporting of adverse events was sparse across studies, precluding firm conclusions regarding safety. Although the reported data did not indicate major tolerability concerns, the certainty of evidence regarding adverse events was rated as low to very low.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterpretation in the context of other evidence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTaken together, our findings do not contradict earlier systematic reviews, which described the evidence for homeopathic interventions in insomnia as limited and inconclusive [10, 11]. Although the magnitude observed in our exploratory, non\u0026ndash;outcome-specific analysis appears comparable to the large effects reported in a recent preprint pooling sleep outcomes [56], this estimate is substantially driven by a single study contributing multiple outcomes and around 50% of the meta-analytic weight. Any alignment between findings should therefore be considered tentative. While a complex systems perspective would predict effects across multiple outcomes rather than a single primary endpoint, the current evidence is insufficient to draw such inferences.\u003c/p\u003e\n\u003cp\u003eAdverse events were infrequent and non-serious, consistent with findings from observational studies [57]. In that review, however, adverse events were systematically monitored and comprehensively reported in most included studies. By contrast, only a minority of trials in the present analysis reported active monitoring of adverse events. Due to a likely absence of reporting, estimates of adverse event frequency remain imprecise.\u003c/p\u003e\n\u003cp\u003eOur assessment of the certainty of evidence was anchored to the null threshold, focusing on the presence of a relative effect rather than its magnitude, in line with established conceptual guidance [41] and considerations for complex interventions [58]. In parallel, and consistent with recent GRADE guidance [59], we examined whether observed point estimates were smaller than the smallest plausible minimal important differences (MIDs) to evaluate whether a target of little or no effect would be more appropriate.\u003c/p\u003e\n\u003cp\u003eFor several outcomes, including total sleep time and sleep onset latency, the absence of established MID values precluded application of this approach. For sleep quality, the observed effect exceeded the proposed MID of 2.5 points [60] and the non-null target was retained. For insomnia severity, published thresholds are heterogeneous and population-specific, and include estimates derived from different instruments or patient populations [61, 62]. Given these limitations, no definitive MID-based target modification was applied. \u0026nbsp;A MID for total sleep duration has recently been proposed [63]; however, its applicability to the present evidence base remains uncertain given the heterogeneity across studies. For sleep onset latency and sleep efficiency, interpretation was further constrained by the lack of established MID thresholds.\u003c/p\u003e\n\u003cp\u003eAgainst this background, the effects observed for homeopathic interventions should be interpreted with caution. The available evidence is constrained by imprecision, heterogeneity, small study numbers, and limited adverse-event reporting, which together preclude firm conclusions regarding both effectiveness and safety. This pattern of findings aligns with current insomnia guidelines, which consistently recommend cognitive behavioral therapy for insomnia (CBT-I) as first-line treatment, while reserving pharmacological therapies for selected patients and typically for short-term use [64, 65].\u003c/p\u003e\n\u003cp\u003eThe preferential position of CBT-I in clinical guidelines is supported by a large and coherent body of evidence demonstrating clinically meaningful and durable improvements in insomnia severity and key sleep parameters [66]. Pharmacological treatments, by contrast, may offer short-term benefits, as shown in network meta-analyses, but require careful benefit\u0026ndash;risk assessment [67]; concerns are particularly pronounced for Z-drugs in older adults, where associations with falls and fractures have been reported [68]. More broadly, the adverse-effect burden of pharmacological insomnia treatments is a clinically relevant reason to prioritize non-pharmacological strategies whenever feasible.\u003c/p\u003e\n\u003cp\u003eAt the same time, CBT-I remains underutilized in routine care due to barriers in access, availability, and implementation [69]. In this context, patient interest in low-threshold and perceived low-risk complementary approaches remains understandable, particularly where patients wish to avoid or minimize exposure to pharmacological treatment [70-72]. However, the current evidence does not allow homeopathy to be positioned as an evidence-based alternative or adjunct in insomnia care.\u003c/p\u003e\n\u003cp\u003eInterpreting the findings of this review through a complexity-informed lens provides additional context for understanding the pronounced heterogeneity observed across studies. Homeopathy, as examined in the included trials, does not constitute a single, uniform intervention but rather encompasses approaches that differ with respect to treatment individualization, prescribing strategies, and trial design.\u003c/p\u003e\n\u003cp\u003eA modified iCAT was applied with the aim of supporting a more structured reflection on intervention complexity within the evidence base [73]; however, limited reporting in the primary studies rarely allowed a differentiated assessment across multiple dimensions. Consequently, its application was largely restricted to a high-level characterization, most notably with respect to treatment individualization, illustrating the challenges of operationalizing complexity-oriented frameworks when key contextual and process-related information is insufficiently reported.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eComplementary assessments of model validity and trial pragmatism further highlighted the heterogeneity of the evidence base. According to the MVHT assessment, fewer than half of the included studies demonstrated acceptable concordance with contemporary homeopathic practice, while the RITES tool indicated a broad spectrum of designs ranging from more explanatory trials to studies with more pragmatic features. Together, these findings indicate that variability in intervention characteristics and study design is a key source of uncertainty in effect estimation and interpretation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrengths and Limitations of the Evidence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results of this review should be interpreted in light of general limitations of the available evidence base. The included studies were predominantly small, frequently exhibited an elevated risk of bias, and showed substantial heterogeneity, including variability in reported outcomes. Several studies were identified as grey literature and demonstrated shortcomings in reporting quality. Only three studies defined their populations according to diagnostic reference standards (Riemann et al., 2022).\u003c/p\u003e\n\u003cp\u003eThe broad inclusion strategy of this review, which encompassed all prospective homeopathy RCTs and NRSIs in insomnia disorder, reflects the characteristics of the existing research field but also entails considerable clinical heterogeneity. This is particularly relevant given the joint consideration of individualized homeopathy and complex preparations and may have contributed to the observed statistical heterogeneity. Even if diagnostic procedures had been more consistently reported, the small number of available studies precluded moderator analyses to assess the influence of these or other factors on effect estimates.\u003c/p\u003e\n\u003cp\u003eAnother limitation is that effectiveness under routine care conditions could not be determined due to the lack of reliable NRSIs. Two of the four identified NRSIs were judged to be at critical risk of bias and were therefore excluded from further analyses. The remaining NRSIs either had a serious risk of bias or a cross-sectional design, which does not allow conclusions regarding real-world effectiveness.\u003c/p\u003e\n\u003cp\u003eIn addition, it was not possible to analyze global measures of symptom improvement or patient satisfaction based on the reported data, outcomes that are of particular relevance for holistic medical approaches such as homeopathy. The exploratory analysis intended to approximate overall symptom reduction by pooling different outcomes is limited, as it combines different constructs and measurement scales [74] and, in this review, is driven to a substantial extent by a single pilot study.\u003c/p\u003e\n\u003cp\u003eThe evidence was further limited by methodological weaknesses in most trials, restricted safety reporting, and scarcity of pediatric data, all of which reduce confidence in the estimates and limit generalizability.\u003c/p\u003e\n\u003cp\u003eOne strength of this review is the comprehensive literature search and non-restrictive inclusion criteria, which reduced the risk of missing relevant studies, including those not published in peer-reviewed journals. All stages of the review were conducted independently by two reviewers. Domain experts were involved in the MVHT and RITES assessments as well as in the clinical evaluation. Patients were involved in the development of both the protocol and the manuscript, and patient perspectives were considered in relation to clinical relevance.\u003c/p\u003e\n\u003cp\u003eAlthough the protocol initially prioritized the CATHIS tool, insufficient inter-rater reliability identified in a parallel validation study [75] necessitated an adapted methodological approach. The use of MVHT and RITES instead allowed a more reliable characterization of intervention fidelity and trial pragmatism based on the available reporting.\u003c/p\u003e\n\u003cp\u003eFinally, PPI improved the accessibility of the review outputs by identifying areas where technical language could limit understanding for non-specialist readers. Feedback also highlighted the importance of clearly communicating uncertainty and safety, which are key concerns for patients considering complementary treatments. Although PPI focused on improving knowledge translation rather than influencing analytical stages of the review, it helped produce a clearer and more accessible summary of the evidence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImplications and conclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOverall, the available evidence for homeopathic treatments for insomnia is limited, and the effects remain uncertain, with no reliable evidence demonstrating a specific therapeutic effect. The existing literature is dominated by small and exploratory studies, many of which exhibit limitations in design and reporting. These shortcomings align with previously documented challenges in internal, external, and model validity within homeopathic clinical research, some of which may be attributable to incomplete or inconsistent reporting rather than study conduct per se [76].\u003c/p\u003e\n\u003cp\u003eFrom a clinical perspective, the current evidence does not provide consistent or high-certainty support for the use of homeopathy as a treatment for insomnia or general sleep disturbances in adults. While certain analyses, particularly for insomnia severity and sleep efficiency, suggest potential benefits, these signals are sensitive to methodological decisions, heterogeneity, and the inclusion of lower-quality studies. Clinicians should therefore exercise caution when considering homeopathy for insomnia and prioritize evidence-based interventions with stronger and more reliable therapeutic profiles. In paediatric populations, where only one open-label trial was available, the very low certainty of evidence and methodological limitations preclude us from providing any clinical recommendation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn this context, additional small or methodologically limited studies are unlikely to substantially advance the evidence base and may continue to contribute only marginally to knowledge accumulation. Future research efforts should therefore focus on a rigorously designed, independently conducted confirmatory replication based on the protocol of Michael et al., which currently represents the only study within the evidence base demonstrating both low risk of bias and acceptable homeopathic model validity. Such a trial should be prospectively registered, strictly adhere to CONSORT reporting standards, and ensure full transparency and reproducibility. In addition to placebo-controlled designs, future studies may also consider comparative effectiveness designs evaluating the incremental benefit of homeopathic treatment as an adjunct to established standard care, such as cognitive behavioral therapy for insomnia.\u003c/p\u003e\n\u003cp\u003eIn line with contemporary frameworks for evidence synthesis of complex and whole medical systems, which emphasize the role of context and complexity, future trials should also systematically capture and report relevant contextual factors, including consultation characteristics, patient expectations and prior experiences with homeopathy, as well as global and patient-reported outcomes such as overall satisfaction [12]. These elements are essential for the adequate evaluation and interpretation of homeopathy as a complex intervention. In addition, trials must incorporate active and systematic surveillance for adverse events to allow a robust assessment of safety.\u003c/p\u003e\n\u003cp\u003eFrom a policy and research governance perspective, these findings support greater methodological standardization, including core outcome sets, trial preregistration, and transparent safety reporting.\u003c/p\u003e\n\u003cp\u003eAt the same time, given the current uncertainty of the evidence, policy decisions regarding the inclusion or exclusion of homeopathy-based interventions for insomnia in public health programs or insurance coverage would benefit from a cautious and proportionate approach. Any future investment in this field should prioritize well-powered, placebo-controlled trials with standardized outcomes and comprehensive adverse-event reporting.\u003c/p\u003e\n\u003cp\u003eAccordingly, in the absence of reproducible evidence meeting these methodological and reporting standards, the specific therapeutic value of homeopathy for insomnia remains uncertain.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003e \u003cstrong\u003eRegistration and protocol\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe protocol was registered under Prospero with the number CRD420251015627.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eProtocol amendments\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe protocol did not specify how insomnia should be operationalized during study selection. Prior to data extraction and analysis, we clarified the population definition by operationalizing insomnia as a primary diagnosis. This was done to distinguish insomnia as the condition under investigation from studies assessing sleep outcomes secondary to other primary conditions. This clarification did not alter the set of included studies.\u003c/p\u003e\n\u003cp\u003eThe DART-Europe e-theses portal, originally planned as a search source, was permanently closed on 3 February 2025. As an alternative, we searched Google Scholar using the search terms \u0026quot;homeopathy insomnia\u0026quot; and screened the first 100 results, sorted by relevance.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBecause a validation study conducted in parallel with the systematic review revealed low interrater reliability of the CATHIS core [75], the instrument was replaced by MVHT and RITES for assessing model validity and clinical relevance; the corresponding methods and results are provided in the project\u0026rsquo;s online repository.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eWe thank Prof. Ashley Hilton Adrian Ross (Durban university of technology, South Africa) for providing raw material of the Naud\u0026eacute; publications, Prof. Liang Yao (Nanyang Technological University, Singapore) for support in assessing GRADE, Dr. Subhranil Saha (D N De Homoeopathic Medical College and Hospital, Kolkata, Govt. of West Bengal. India) for participating in the CATHIS core assessment, and Dr. Hebatullah Mohamed Abdulazeem (Technical University of Munich, Germany) for helpful comments.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eSupport\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThis study was supported by the Software AG Stiftung, Darmstadt, Germany.\u003c/p\u003e\n\u003cp\u003eSK has been financed by the Ursimone Wietlisbach Foundation.\u003c/p\u003e\n\u003ch2\u003eDeclaration of generative AI and AI-assisted technologies in the writing process\u003c/h2\u003e\n\u003cp\u003eArtificial intelligence tools were accessed via web interface to draft a plain language summary, to refine the language and structure of the manuscript, and to support R code debugging and optimization. OpenAI ChatGPT (version 5.2; February 2026) generated an initial draft of the plain language summary which was revised by the authors. A GPT-5 series ChatGPT model (November 2025\u0026ndash;March 2026) was used for language editing, restructuring for clarity, and consistency checks against cited literature within the manuscript. All AI-generated outputs were critically reviewed and verified by the authors, who retain full responsibility for the content, methods, and conclusions of the review.\u003c/p\u003e\n\u003ch2\u003eConflict of interest\u003c/h2\u003e\n\u003cp\u003eDS, SK, PW, and ML declare that no competing financial interests exist. AD, DW, PW, KG work as homeopathic doctors. RvH provided consultancy services to Heel Biologische Heilmittel GmbH, a manufacturer of Homeopathic Preparations, and to the \u0026apos;European Coalition on Homeopathic and Anthroposophic Medicinal Products\u0026apos; (ECHAMP), which is a European Economic Interest Grouping (EEIG) of companies active in the production and distribution of Homeopathic Products. As an employee of the Government of India, AD declares that the views and contribution expressed in this article are his own and do not necessarily reflect the official policy or position of the Ministry of Ayush or the Government of India.\u003c/p\u003e\n\u003ch2\u003eData Availability Statement\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe data supporting the findings of this study are available as supplementary material with this article and/or will be made openly accessible on the Open Science Framework (OSF) at osf.io/bnk5t.\u003c/p\u003e\n\u003cp\u003eThis review will be maintained as a living systematic review. Searches will be re-run at least annually, and updates will be issued when new evidence is likely to affect the conclusions. The living mode will be continued only as long as relevant new research emerges and resources permit. Details will be made available at the following website: homeopathy-evidence.info.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAmerican Academy of Sleep, M., \u003cem\u003eInternational classification of sleep disorders\u0026mdash;third edition (ICSD-3)\u003c/em\u003e. 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Homeopathy has been proposed as a complementary treatment for insomnia, but its clinical effects remain uncertain. This systematic review assessed the efficacy, effectiveness, and safety of homeopathic treatments for insomnia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: Prospective comparative studies evaluating any homeopathic preparation for insomnia were included. Searches in MEDLINE, EMBASE, seven additional databases, and three trial registries were conducted through August 2025. Risk of bias, intervention complexity, model validity, and pragmatism were assessed using respectively RoB 2, ROBINS-I, iCAT, MVHT, and RITES. Data were synthesized using random-effects meta-analyses, and certainty of evidence was evaluated using GRADE.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Eight randomized controlled trials (RCTs; n = 364 participants) and four non-randomized studies on interventions (NRSIs; n = 517) met the inclusion criteria. In adults, sleep quality (MD = −2.6 points; 95% CI −5.5 to 2.6; low certainty) and insomnia severity (MD = −3.2; 95% CI −5.68 to −0.72, moderate certainty) were reported in one RCT each. For total sleep time, the pooled MD of three RCTs was 0.65 hours (95% CI −0.9 to 2.2; low certainty). In children, one open-label RCT suggested a difference in insomnia severity, but certainty of evidence was very low. Adverse events were rarely reported, resulting in low certainty evidence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: The current evidence is mainly limited by imprecision and risk of bias. The available evidence does not allow firm conclusions regarding the effects of homeopathy for insomnia. High-quality, replicated trials with systematic adverse-event monitoring are needed\u003cem\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRegistration\u003c/strong\u003e: Prospero 2025 CRD420251015627\u003c/p\u003e","manuscriptTitle":"Homeopathy for the Treatment of Insomnia: A Systematic Review and Meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-21 15:22:05","doi":"10.21203/rs.3.rs-9439398/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"07abe67b-dd49-4f26-9864-bf188f87b070","owner":[],"postedDate":"April 21st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-24T18:24:10+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-21 15:22:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9439398","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9439398","identity":"rs-9439398","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}