High adherence to pharmacological treatment guidelines in recovery and remission states among patients with schizophrenia: A cross-sectional study

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However, no studies have examined recovery and pharmacological therapy or guideline adherence's impact on various schizophrenia states. This study aimed to investigate adherence to pharmacological guidelines across recovery, remission, and non-remission states in patients with schizophrenia. Methods This cross-sectional study included 72 patients with schizophrenia who met the criteria for recovery, remission, or non-remission. Adherence to pharmacological guidelines was measured using the Individual Fitness Score (IFS). Results IFS was significantly higher in the recovery (88.1 ± 18.9) and remission (89.0 ± 16.7) groups than in the non-remission group (65.59 ± 21.8) (p < 0.01). However, no significant differences were observed between the recovery and remission groups. Receiver operating characteristic (ROC) analysis identified 72 points on the IFS as a potential cutoff point between remission and non-remission. Conclusion These results indicate that adherence to pharmacological guidelines may contribute to achieving remission from non-remission, and an IFS of 72 could be an indicator of pharmacotherapy, though it may not be enough to achieve recovery in patients with schizophrenia. Clinical practice guidelines have been developed to standardize and improve the quality of medical care, and several schizophrenia guidelines have been published worldwide. Treatments following these guidelines have been reported to be effective. Guideline Pharmacotherapy Schizophrenia Recovery Remission Non-remission Figures Figure 1 Figure 2 Background Several guidelines for schizophrenia have been published, and treatments based on these guidelines and algorithms have been shown to be effective in patients with schizophrenia [ 1 ], [ 2 ]. In schizophrenia pharmacotherapy, many guidelines recommend antipsychotic monotherapy to minimize the side effects of antipsychotics or other psychotropics [ 3 ] [ 4 ] [ 5 ]. In Japan, pharmacological therapy guidelines for schizophrenia have been published by the Japanese Society of Neuropsychopharmacology (JSNP) [ 5 ]. These guidelines recommend second-generation antipsychotic (SGA) monotherapy without the combination of other psychotropic drugs for acute and chronic patients with schizophrenia. The individual fitness score (IFS) is a new tool used to evaluate schizophrenia treatment adherence to guidelines [ 6 ] and assess compliance with the JSNP guidelines. Previous studies using the IFS to evaluate adherence to these guidelines showed that high adherence may contribute to improved psychiatric symptoms [ 7 ] and working time [ 8 ]. Recovery after achieving remission is considered one of the goals of patients with schizophrenia. Recovery involves improving symptoms, social function, and personal relationships [ 9 ]. However, a systematic review reported a recovery rate of 13.5% [ 10 ], which has remained low compared with the remission rate [ 11 ]. Furthermore, to the best of our knowledge, no studies have examined the relationship between recovery in schizophrenia and pharmacological therapy. In addition, previous studies using the IFS evaluated treatment-resistant schizophrenia (TRS) and non-TRS [ 7 ] [ 8 ]; however, no evidence has demonstrated that adherence to guidelines contributes to several states of schizophrenia, including recovery or remission. Thus, adherence to the guidelines may improve psychiatric symptoms, including hallucinations or delusions. However, it remains unclear whether adherence to the guidelines contributes to achieving recovery or remission in patients with schizophrenia. We hypothesized that the IFS would differ depending on the state, such as recovery, remission, and non-remission, in patients with schizophrenia, and some points on the IFS could be indicators to differentiate between these groups. Therefore, this study aimed to compare the IFS across recovery, remission, and non-remission patients with schizophrenia. The secondary purpose was to evaluate the cutoff points for each group. Methods Participants This cross-sectional study recruited participants from five psychiatric institutions (Fukuoka University Hospital, Aburayama Hospital, Rainbow and Sea Hospital, Kawano Clinic, and UNB Sumiyoshi Jinja Mae Clinic in Japan) between 2021 and 2024. In total, 72 Japanese patients with schizophrenia were enrolled in this study. The inclusion criteria were as follows: 1) diagnosis of schizophrenia based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria [ 12 ], 2) age 20–65 years; 3) no change in the dose of antipsychotics for ≥ 3 months; 4) not taking anticholinergic drugs; and 5) willingness to provide written informed consent. The exclusion criteria were as follows: 1) history of trauma with loss of consciousness or serious organic disease, including central nervous system diseases, and 2) diagnosis of substance-related and addictive disorders based on the DSM-5 [ 12 ]. We collected clinical (medication prescriptions, duration of illness, age of onset, and number of admissions) and demographic data (age, sex, body mass index (BMI), marital status, smoking, and duration of education or employment) from medical records and interviewed the participants. Clinical trial number: not applicable. Definition of recovery, remission, and non-remission The definition of recovery in patients with schizophrenia is based on established criteria [ 9 ]. This criterion consisted of the following components: 1) symptoms: score ≤ 4 on the positive and negative symptoms assessed by the Brief Psychiatric Rating Scale (BPRS) [ 13 ]; 2) vocational function: successful employment in a competitive job or attending school at least half-time; 3) independent living: living independently without daily supervision; 4) peer relationships: engaging in social interactions with people outside the family at least once per week, maintained for ≥ 2 years. Symptomatic remission was defined by the following criteria [ 14 ]: a score ≤ 3 on the items associated with positive symptoms (items 8, 11, and 15), disorganization (items 4 and 7), and negative symptoms (item 16) on the BPRS, maintained for ≥ 6 months. Non-remission was defined as not meeting the recovery, remission, or TRS criteria. TRS criteria were defined as not improving a Global Functioning Assessment (GAF) ≧ 41 despite the use of ≥ two antipsychotics (Chlorpromazine (CPZ) equivalent dose of 600 mg or more) for at least 4 weeks. Participants were categorized into three groups using the following procedure: Participants who met the recovery criteria were defined as the recovery group. Patients who did not meet the recovery criteria and met the remission criteria were assigned to the remission group. Those who did not meet the remission and TRS criteria were included in the non-remission group. Evaluation of adherence to the guidelines The IFS (see Table 1 by [ 6 ]) was used to evaluate adherence to the guidelines. The IFS calculations differed for non-TRS and TRS; in this study, we used the non-TRS version. A prescription of SGA monotherapy below the maximum therapeutic dose (MTD) was scored 100 points without deduction. If SGA monotherapy exceeded the appropriate dose, the IFS was calculated as follows: 25 points were deducted for doses within 1.5 × MTD and 50 points for doses exceeding 1.5 MTD. For SGA polypharmacy involving two agents, the IFS was calculated as follows: 25 points were deducted for CPZ equivalents ≤ 1000, 35 points for CPZ equivalents > 1000 and ≤ 2000, and 50 points for CPZ equivalent > 2000. For SGA polypharmacy involving ≥ three agents, 65 points were deducted. Regarding first-generation antipsychotic (FGA) monotherapy, the IFS was calculated as follows: 5 points were deducted within the MTD, 30 points for doses exceeding the MTD within 1.5 × MTD, and 55 points for doses exceeding 1.5 × MTD. For FGA polypharmacy involving two agents, the IFS was calculated as follows: 35 points were deducted for CPZ equivalents ≤ 1000, 45 points for CPZ equivalents > 1000 ≤ 2000, and 60 points for CPZ equivalents > 2000. Regarding SGA- FGA combination therapy, the IFS was calculated as follows: 30 points were deducted for CPZ equivalents ≤ 1000, 40 points for CPZ equivalents > 1000 ≤ 2000, and 55 points for CPZ equivalents > 2000. For SGA and FGA polypharmacy involving ≥ three agents, 70 points were deducted. For concomitant prescription of antidepressants, anxiolytic hypnotics, mood stabilizers, antiepileptic drugs, and other psychotropic drugs (except dopaminergic and anticholinergic drugs), the IFS was calculated as follows: 15 points were deducted for one drug, 35 points for two drugs, and 55 points for ≥ three drugs. For concomitant medication with dopaminergic drugs (dopaminergic anti-parkinsonian drugs and psychostimulants), 80 points were deducted per drug. The IFS ranged from 0 to 100, with higher scores indicating greater adherence to the guidelines. Table 1 Demographics, clinical characteristics and IFS among each schizophrenia group. Recovery Remission Non-Remission SD SD SD pValue Post hoc Sex (male/female) 11/13 11/19 11/7 0.258 Age (year) 43.3 10.3 39.1 10.9 44.8 13.0 0.193 BMI 23.6 3.9 26.1 5.0 25.3 4.3 0.619 Education (year) 14.1 1.8 13.6 2.4 13.9 2.3 0.619 Duration of employment (year) 14.5 9.7 6.1 7.1 5.4 7.1 REM > NREM Smoking (yes/no) 4/20 4/25 6/12 0.321 Marital status (single/married/divorced) 14 / 9 / 1 23 / 4 / 3 15 / 2 / 1 0.160 Duration of illness (year) 17.2 8.9 11.5 7.9 15.8 11.3 0.003 NREM > REM Average daily dosage (CPZ-equivalent, mg/day) 355.0 196.7 405.5 174.3 543.2 223.5 0.003 NREM > REC Number of admission 1.8 1.2 1.1 0.7 4.1 3.1 0.001 NREM > REM Age at onset (year) 26.0 7.4 27.7 9.5 23.3 6.0 0.369 GAF 73.2 5.8 59.9 7.0 51.3 6.7 REM > NREM BPRS 29.4 6.2 30.0 5.3 43.4 8.0 REC, REM CDSS 1.1 1.2 2.9 3.0 4.6 3.7 0.005 NREM > REC, REM IFS 88.1 18.9 89.0 16.7 65.9 21.8 NREM BMI: body Mass Index, CPZ- equivalent: Chlorpromazine equivalent, GAF: Global Functioning Assessment, BPRS: Brief Psychiatric Rating Scale, CDSS: Calgary Depression Scale for Schizophrenia, IFS: Individual fitness score, REC: Recovery, REM: Remission, NREM: Non-remission Psychiatric symptoms Psychiatric symptoms were assessed using the BPRS and Calgary Depression Scale for Schizophrenia (CDSS) [ 15 ]. The BPRS comprises 18 items, each scored on a scale from 1 (not present) to 7 (most severe), with a total score ranging from 18 to 126. Higher scores indicated severe psychiatric symptoms. The CDSS, which consists of nine items, was used to assess depressive symptoms in schizophrenia. Each scale ranged from 0 to 2, with higher scores indicating more severe depressive symptoms. Evaluation of functions The GAF has been widely used to evaluate symptoms and social functioning in psychiatric illnesses [ 16 ]. The score ranged from 0 to 100, with a high score suggesting milder symptoms and higher functions. Statistical analysis The recovery, remission, and non-remission groups included 24, 30, and 18 patients, respectively. The Statistical Package for the Social Sciences version 27.0 was used for data analysis. The chi-square test was used for categorical variables, including sex, smoking, and marital status. The Shapiro‒Wilk test was used to analyze normality. Age, BMI, and BPRS followed a normal distribution and were analyzed using a one-way analysis of variance. Education, duration of employment, duration of illness, average daily dose, number of admissions, age at onset, GAF, CDSS, and IFS did not follow a normal distribution and were analyzed using the Kruskal‒Wallis test. The Bonferroni correction was used for post-hoc comparisons. The IFS cutoff points between the remission and non-remission groups were determined using ROC curve analysis. Statistical significance was set at p < 0.05. Results Demographic data The clinical characteristics and demographics of each group are shown in Table 1 . Significant differences were observed in duration of employment, duration of illness, average daily dose, and number of admissions between the groups. The duration of illness was significantly higher in the non-remission group than in the remission group; however, the duration of illness was not significantly different between the recovery and remission or non-remission groups. The average daily dose in the non-remission group was significantly higher than that in the recovery group; however, no significant difference was observed between the recovery and remission or remission and non-remission groups. The BPRS and CDSS scores of the non-remission group were significantly higher than those of the recovery and remission groups. However, no significant difference was observed between the recovery and remission groups. The GAF score in the recovery group was significantly higher than that in the remission group and significantly higher in the remission group than in the non-remission group. Comparison of IFS between three groups Figure 1 presents the comparison of IFS between the three groups, showing significantly higher IFS in recovery and remission groups than in the non-remission group (p < 0.01). In the post hoc test, the IFS was significantly higher in the recovery group than in the non-remission group (p < 0.01), and the IFS of the remission group was also significantly higher than that of the non-remission group (p < 0.01). Conversely, no significant difference was observed in the IFS between the recovery and remission groups (p = 0.86). Correlation between IFS and clinical characteristics Table 2 shows the correlation between IFS and demographic or clinical characteristics across the groups. No significant correlation was observed, except for the age of onset in the recovery group. Table 2 Correlation between IFS and clinical characteristics among each schizophrenia group. Recovery Remission Non-remission r p-Value r p-Value r p-Value Age (year) -0.155 0.471 -0.070 0.712 -0.168 0.506 BMI -0.305 0.147 0.129 0.497 -0.238 0.341 Education (year) -0.023 0.914 0.117 0.537 -0.234 0.350 Duration of employment (year) -0.369 0.076 -0.022 0.909 0.441 0.067 Duration of illness (year) 0.017 0.937 -0.092 0.628 -0.371 0.129 Average daily dosage (CPZ-equivalent, mg/day) -0.131 0.543 -0.011 0.954 -0.049 0.846 Number of admissions 0.011 0.961 -0.157 0.407 -0.211 0.401 Age at onset (year) -0.572 0.004 -0.030 0.875 0.180 0.475 GAF -0.027 0.901 0.102 0.593 0.397 0.115 BPRS -0.195 0.361 -0.094 0.623 0.194 0.441 CDSS 0.067 0.754 -0.176 0.351 0.152 0.547 CPZ- equivalent: Chlorpromazine equivalent, GAF: Global Functioning Assessment, BPRS: Brief Psychiatric Rating Scale, CDSS: Calgary Depression Scale for Schizophrenia ROC analysis of remission and non-remission group Based on the ROC curve, an IFS cutoff point of 72 showed 83.3% sensitivity and 67.67% specificity, with an area under the curve of 81% (Fig. 2 ). Discussion This is the first study to evaluate the association between guideline adherence and the state of patients with schizophrenia. We found that the IFS in patients with schizophrenia in recovery and remission was significantly higher than that in patients with schizophrenia in non-remission. In addition, an IFS cutoff of 72 points may help distinguish between remission and non-remission pharmacotherapy. However, no significant difference in IFS was observed between the recovery and remission groups. In recovery and remission patients with schizophrenia, adherence to guidelines was higher than that in non-remission patients; however, no significant difference in IFS was observed between the recovery and remission groups. This suggests that adherence to the guidelines may contribute to achieving remission in patients with schizophrenia. This study suggests that adherence to the guidelines may be effective, as indicated in previous studies [ 7 ] [ 8 ]. However, this study uniquely evaluated the different states of schizophrenia, including recovery, remission, and non-remission. A Japanese prescription survey showed that 43% of patients received antipsychotic polypharmacy, and 85% of patients were prescribed antipsychotics and other psychotropics, including hypnotic or antianxiety medications, antidepressants, and mood stabilizers [ 17 ]. Another study showed that the rate of polypharmacy in Japan was higher to that in other countries [ 18 ]. We considered that the number of antipsychotics or concomitant use of psychotropics might have a greater influence on the difference in IFS than the dose of antipsychotics, as the CPZ equivalent was < 600 mg/day across the three groups in the present study. Furthermore, this study showed that an IFS of 72 points was the cutoff for distinguishing remission and non-remission schizophrenia. Several guidelines have outlined the appropriate dose and duration of antipsychotics [ 3 ] [ 4 ]; however, no indicator exists for the overall prescription for each patient. This result may provide a clinical target for achieving remission in non-remission patients with schizophrenia. No significant difference in IFS was observed between the recovery and remission states. Our findings showed that adherence to the guidelines was not sufficient to achieve recovery, which may indicate limitations in the guidelines for pharmacological therapy. The IFS of recovery and remission were higher than those in previous reports comparing [ 7 ] [ 8 ], and we considered that adherence to the guidelines remained important. Conversely, the results of this study indicate that psychosocial factors are more important than pharmacotherapy for achieving recovery from remission. In fact, several psychological interventions, such as cognitive remediation, psychoeducation, social skills training, and cognitive behavioral therapy, were useful for improving social functions and preventing relapse [ 19 ]. Psychological interventions may need to be implemented to achieve recovery from remission. This study indicated that the IFS has two aspects in evaluating pharmacotherapy, serving as a comprehensive evaluation tool for prescriptions and therapeutic indicators. First, the JSNP guideline includes some recommendations, regarding the number of medications, dose of antipsychotics, and concomitant use of psychotropics [ 5 ], and IFS could evaluate these quality indicators (QIs) simultaneously. The difference in IFS may indicate a comprehensive adherence to these QIs, and we considered that adherence to multiple QIs may contribute to achieving remission in patients with schizophrenia. However, the IFS of the recovery and remission groups also suggest that complete adherence to the guidelines may not necessarily contribute to achieving recovery or remission in patients with schizophrenia. In fact, some studies have reported the efficacy of antipsychotic polypharmacy for positive symptoms or the prevention of rehospitalization [ 20 ] [ 21 ], and combining antipsychotics and antidepressants improved negative symptoms in patients with schizophrenia [ 22 ]. While adherence to treatment guidelines is generally beneficial, some clinical situations may require individualized modifications, such as dose adjustments or selective polypharmacy, to achieve optimal outcomes. Second, the IFS could be used as a clinical indicator for pharmacotherapy. We clearly showed the cutoff points between remission and non-remission in patients with schizophrenia. Only a few biomarkers are associated with remission in patients with schizophrenia [ 23 ]. This study suggests that an IFS ≥ 72 points may be an indicator of comprehensive pharmacotherapy for achieving remission in these patients. Based on these findings, we propose the “Remission criterion,” where an IFS of 72 points is the cutoff for remission in patients with schizophrenia. In the future, if various IFS cutoff points depended on the state are known, an appropriate pharmacotherapy targeting IFS for each patient with schizophrenia may be proposed. Thus, the IFS may serve not only as a tool for evaluating adherence to guidelines but also as a clinical target for pharmacotherapy across different states in patients with schizophrenia. This study has some limitations. First, the cross-sectional study design could not reveal causality between the IFS and recovery, remission, and non-remission states; longitudinal studies are needed to assess causality. Second, the sample size was relatively small, and the results should be evaluated in a larger-scale study. Third, these results were influenced by the differences in education for psychiatrists, difference of treatment approach at each institution or the trend of psychotropics prescription because this study was conducted at five psychiatric institutions in Japan. Conclusion This study clearly showed high adherence to guidelines in patients in recovery and remission states of schizophrenia, compared with those in non-remission states, and no significant difference in IFS was observed between recovery and remission. In addition, an IFS of 72 could be a cutoff point, distinguishing between remission and non-remission. This study emphasized that adherence to guidelines is important for recovery and remission; however, psychological factors may be crucial for achieving recovery from remission. We believe that assessing IFS in long-term individual studies with large-scale samples is necessary. Abbreviations BMI Body Mass Index BPRS Brief Psychiatric Rating Scale CDSS Calgary Depression Scale for Schizophrenia CPZ Chlorpromazine DSM-5 Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition FGA First-Generation Antipsychotic GAF Global Functioning Assessment IFS Individual Fitness Score JSNP Japanese Society of Neuropsychopharmacology MTD Maximum Therapeutic Dose QIs Quality Indicator SGA Second-Generation Antipsychotic TRS Treatment-Resistant Schizophrenia Declarations Ethics approval and consent to participate This study was approved by the Fukuoka University Medical Ethics Review Board (approval number: U21-11-018), and all patients provided written informed consent before participation in this study. This study was conducted in accordance with to the latest version of the Declaration of Helsinki. Consent for publication Not applicable. Funding This work was supported by the Grant of The Clinical Research Promotion Foundation (2022). Author Contribution RA: Conceptualization, Software, Validation, Formal analysis, Investigation, Resources, Data Curation, Writing – Original Draft, Visualization, Project administration, Funding acquisition. HI: Methodology, Writing – Review & Editing. LG: Validation, Investigation, Writing – Review & Editing. KY: Data Curation. HH: Conceptualization, Methodology, Validation, Data Curation, Writing – Review & Editing, Supervision. All the authors have read and approved the final manuscript. Acknowledgements Not applicable. Availability of data and materials The datasets analyzed during the current study are not publicly available due to the lack of informed consent for the release of raw data but are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. References O'Donoghue B, Piacenza F, Plapp H, Siskind D, Lyne J. 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Efficacy and tolerability of antipsychotic polypharmacy for schizophrenia spectrum disorders. A systematic review and meta-analysis of individual patient data. Schizophr Res. 2024;272:1–11. Tiihonen J, Taipale H, Mehtala J, Vattulainen P, Correll CU, Tanskanen A. Association of Antipsychotic Polypharmacy vs Monotherapy With Psychiatric Rehospitalization Among Adults With Schizophrenia. JAMA Psychiatry. 2019;76(5):499–507. Galling B, Vernon JA, Pagsberg AK, Wadhwa A, Grudnikoff E, Seidman AJ, et al. Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia. Acta Psychiatr Scand. 2018;137(3):187–205. Asada R, Hori H, Gotoh L, Yasumatsu K, Iida H, Kawasaki H. Lower plasma tumor necrosis factor-alpha is associated with symptomatic remission in patients with schizophrenia. J Psychiatr Res. 2024;177:299–304. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6677621","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":501158640,"identity":"0afc128a-4f81-4ad7-844c-82b90cdbe1f7","order_by":0,"name":"Ryo Asada","email":"","orcid":"","institution":"Fukuoka University","correspondingAuthor":false,"prefix":"","firstName":"Ryo","middleName":"","lastName":"Asada","suffix":""},{"id":501158641,"identity":"960b011c-0a8e-4503-95ef-6e76fbbd1184","order_by":1,"name":"Hitoshi Iida","email":"","orcid":"","institution":"Fukuoka University","correspondingAuthor":false,"prefix":"","firstName":"Hitoshi","middleName":"","lastName":"Iida","suffix":""},{"id":501158642,"identity":"c60e0345-2725-49ef-95c7-024b0147c9fd","order_by":2,"name":"Leo Gotoh","email":"","orcid":"","institution":"Fukuoka University","correspondingAuthor":false,"prefix":"","firstName":"Leo","middleName":"","lastName":"Gotoh","suffix":""},{"id":501158643,"identity":"9fca7ec5-5336-43f3-859a-0d74cc7fe183","order_by":3,"name":"Kiyohiro Yasumatsu","email":"","orcid":"","institution":"Fukuoka University","correspondingAuthor":false,"prefix":"","firstName":"Kiyohiro","middleName":"","lastName":"Yasumatsu","suffix":""},{"id":501158644,"identity":"b3db9da1-d1fb-4f71-8186-8663d2e0b3c5","order_by":4,"name":"Hikaru Hori","email":"data:image/png;base64,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","orcid":"","institution":"Fukuoka University","correspondingAuthor":true,"prefix":"","firstName":"Hikaru","middleName":"","lastName":"Hori","suffix":""}],"badges":[],"createdAt":"2025-05-16 06:23:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6677621/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6677621/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89570172,"identity":"18a39aa8-5e35-4234-aef3-fc9fb278e852","added_by":"auto","created_at":"2025-08-21 12:03:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":90900,"visible":true,"origin":"","legend":"\u003cp\u003eThe comparison of IFS among recovery, remission and non-remission groups.\u003c/p\u003e\n\u003cp\u003eIFS: Individual fitness score\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-6677621/v1/c3dc796e327f8637e6bb28a0.png"},{"id":89570173,"identity":"f3a38932-f7f1-494f-b0cb-a58364211bb4","added_by":"auto","created_at":"2025-08-21 12:03:38","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":84183,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for cut off between remission and non-remission schizophrenia group\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-6677621/v1/cd41a80fab3bea2d09c703c8.png"},{"id":104400748,"identity":"0d14bba9-6f26-4f71-868a-0249f9459e63","added_by":"auto","created_at":"2026-03-11 12:10:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":855620,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6677621/v1/c4e40859-df3b-40a5-bf91-2a55c7198b14.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"High adherence to pharmacological treatment guidelines in recovery and remission states among patients with schizophrenia: A cross-sectional study","fulltext":[{"header":"Background","content":"\u003cp\u003eSeveral guidelines for schizophrenia have been published, and treatments based on these guidelines and algorithms have been shown to be effective in patients with schizophrenia [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In schizophrenia pharmacotherapy, many guidelines recommend antipsychotic monotherapy to minimize the side effects of antipsychotics or other psychotropics [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In Japan, pharmacological therapy guidelines for schizophrenia have been published by the Japanese Society of Neuropsychopharmacology (JSNP) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These guidelines recommend second-generation antipsychotic (SGA) monotherapy without the combination of other psychotropic drugs for acute and chronic patients with schizophrenia. The individual fitness score (IFS) is a new tool used to evaluate schizophrenia treatment adherence to guidelines [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and assess compliance with the JSNP guidelines. Previous studies using the IFS to evaluate adherence to these guidelines showed that high adherence may contribute to improved psychiatric symptoms [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and working time [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRecovery after achieving remission is considered one of the goals of patients with schizophrenia. Recovery involves improving symptoms, social function, and personal relationships [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, a systematic review reported a recovery rate of 13.5% [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], which has remained low compared with the remission rate [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Furthermore, to the best of our knowledge, no studies have examined the relationship between recovery in schizophrenia and pharmacological therapy. In addition, previous studies using the IFS evaluated treatment-resistant schizophrenia (TRS) and non-TRS [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]; however, no evidence has demonstrated that adherence to guidelines contributes to several states of schizophrenia, including recovery or remission.\u003c/p\u003e\u003cp\u003e Thus, adherence to the guidelines may improve psychiatric symptoms, including hallucinations or delusions. However, it remains unclear whether adherence to the guidelines contributes to achieving recovery or remission in patients with schizophrenia. We hypothesized that the IFS would differ depending on the state, such as recovery, remission, and non-remission, in patients with schizophrenia, and some points on the IFS could be indicators to differentiate between these groups. Therefore, this study aimed to compare the IFS across recovery, remission, and non-remission patients with schizophrenia. The secondary purpose was to evaluate the cutoff points for each group.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eParticipants\u003c/h2\u003e\u003cp\u003e This cross-sectional study recruited participants from five psychiatric institutions (Fukuoka University Hospital, Aburayama Hospital, Rainbow and Sea Hospital, Kawano Clinic, and UNB Sumiyoshi Jinja Mae Clinic in Japan) between 2021 and 2024. In total, 72 Japanese patients with schizophrenia were enrolled in this study. The inclusion criteria were as follows: 1) diagnosis of schizophrenia based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], 2) age 20\u0026ndash;65 years; 3) no change in the dose of antipsychotics for \u0026ge;\u0026thinsp;3 months; 4) not taking anticholinergic drugs; and 5) willingness to provide written informed consent. The exclusion criteria were as follows: 1) history of trauma with loss of consciousness or serious organic disease, including central nervous system diseases, and 2) diagnosis of substance-related and addictive disorders based on the DSM-5 [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. We collected clinical (medication prescriptions, duration of illness, age of onset, and number of admissions) and demographic data (age, sex, body mass index (BMI), marital status, smoking, and duration of education or employment) from medical records and interviewed the participants.\u003c/p\u003e\u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eDefinition of recovery, remission, and non-remission\u003c/h3\u003e\n\u003cp\u003eThe definition of recovery in patients with schizophrenia is based on established criteria [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This criterion consisted of the following components: 1) symptoms: score\u0026thinsp;\u0026le;\u0026thinsp;4 on the positive and negative symptoms assessed by the Brief Psychiatric Rating Scale (BPRS) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]; 2) vocational function: successful employment in a competitive job or attending school at least half-time; 3) independent living: living independently without daily supervision; 4) peer relationships: engaging in social interactions with people outside the family at least once per week, maintained for \u0026ge;\u0026thinsp;2 years.\u003c/p\u003e\u003cp\u003eSymptomatic remission was defined by the following criteria [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]: a score\u0026thinsp;\u0026le;\u0026thinsp;3 on the items associated with positive symptoms (items 8, 11, and 15), disorganization (items 4 and 7), and negative symptoms (item 16) on the BPRS, maintained for \u0026ge;\u0026thinsp;6 months.\u003c/p\u003e\u003cp\u003eNon-remission was defined as not meeting the recovery, remission, or TRS criteria. TRS criteria were defined as not improving a Global Functioning Assessment (GAF)\u0026thinsp;≧\u0026thinsp;41 despite the use of \u0026ge;\u0026thinsp;two antipsychotics (Chlorpromazine (CPZ) equivalent dose of 600 mg or more) for at least 4 weeks.\u003c/p\u003e\u003cp\u003eParticipants were categorized into three groups using the following procedure: Participants who met the recovery criteria were defined as the recovery group. Patients who did not meet the recovery criteria and met the remission criteria were assigned to the remission group. Those who did not meet the remission and TRS criteria were included in the non-remission group.\u003c/p\u003e\n\u003ch3\u003eEvaluation of adherence to the guidelines\u003c/h3\u003e\n\u003cp\u003eThe IFS (see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e by [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]) was used to evaluate adherence to the guidelines. The IFS calculations differed for non-TRS and TRS; in this study, we used the non-TRS version. A prescription of SGA monotherapy below the maximum therapeutic dose (MTD) was scored 100 points without deduction. If SGA monotherapy exceeded the appropriate dose, the IFS was calculated as follows: 25 points were deducted for doses within 1.5 \u0026times; MTD and 50 points for doses exceeding 1.5 MTD. For SGA polypharmacy involving two agents, the IFS was calculated as follows: 25 points were deducted for CPZ equivalents\u0026thinsp;\u0026le;\u0026thinsp;1000, 35 points for CPZ equivalents\u0026thinsp;\u0026gt;\u0026thinsp;1000 and \u0026le;\u0026thinsp;2000, and 50 points for CPZ equivalent\u0026thinsp;\u0026gt;\u0026thinsp;2000. For SGA polypharmacy involving\u0026thinsp;\u0026ge;\u0026thinsp;three agents, 65 points were deducted. Regarding first-generation antipsychotic (FGA) monotherapy, the IFS was calculated as follows: 5 points were deducted within the MTD, 30 points for doses exceeding the MTD within 1.5 \u0026times; MTD, and 55 points for doses exceeding 1.5 \u0026times; MTD. For FGA polypharmacy involving two agents, the IFS was calculated as follows: 35 points were deducted for CPZ equivalents\u0026thinsp;\u0026le;\u0026thinsp;1000, 45 points for CPZ equivalents\u0026thinsp;\u0026gt;\u0026thinsp;1000\u0026thinsp;\u0026le;\u0026thinsp;2000, and 60 points for CPZ equivalents\u0026thinsp;\u0026gt;\u0026thinsp;2000. Regarding SGA- FGA combination therapy, the IFS was calculated as follows: 30 points were deducted for CPZ equivalents\u0026thinsp;\u0026le;\u0026thinsp;1000, 40 points for CPZ equivalents\u0026thinsp;\u0026gt;\u0026thinsp;1000\u0026thinsp;\u0026le;\u0026thinsp;2000, and 55 points for CPZ equivalents\u0026thinsp;\u0026gt;\u0026thinsp;2000. For SGA and FGA polypharmacy involving\u0026thinsp;\u0026ge;\u0026thinsp;three agents, 70 points were deducted. For concomitant prescription of antidepressants, anxiolytic hypnotics, mood stabilizers, antiepileptic drugs, and other psychotropic drugs (except dopaminergic and anticholinergic drugs), the IFS was calculated as follows: 15 points were deducted for one drug, 35 points for two drugs, and 55 points for \u0026ge;\u0026thinsp;three drugs. For concomitant medication with dopaminergic drugs (dopaminergic anti-parkinsonian drugs and psychostimulants), 80 points were deducted per drug. The IFS ranged from 0 to 100, with higher scores indicating greater adherence to the guidelines.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographics, clinical characteristics and IFS among each schizophrenia group.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRecovery\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRemission\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNon-Remission\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003epValue\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ePost hoc\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex (male/female)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11/13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11/19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11/7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.258\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e43.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e39.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e10.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e44.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.193\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e25.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.619\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation (year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.619\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration of employment (year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eREC\u0026thinsp;\u0026gt;\u0026thinsp;REM\u0026thinsp;\u0026gt;\u0026thinsp;NREM\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking (yes/no)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4/20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4/25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.321\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMarital status (single/married/divorced)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 / 9 / 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23 / 4 / 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e15 / 2 / 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.160\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration of illness (year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e15.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e11.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNREM\u0026thinsp;\u0026gt;\u0026thinsp;REM\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAverage daily dosage \u003c/p\u003e\u003cp\u003e(CPZ-equivalent, mg/day)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e355.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e196.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e405.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e174.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e543.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e223.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNREM\u0026thinsp;\u0026gt;\u0026thinsp;REC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of admission\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNREM\u0026thinsp;\u0026gt;\u0026thinsp;REM\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at onset (year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e23.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.369\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGAF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e73.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e59.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e51.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eREC\u0026thinsp;\u0026gt;\u0026thinsp;REM\u0026thinsp;\u0026gt;\u0026thinsp;NREM\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBPRS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e43.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNREM\u0026thinsp;\u0026gt;\u0026thinsp;REC, REM\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCDSS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNREM\u0026thinsp;\u0026gt;\u0026thinsp;REC, REM\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIFS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e88.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e89.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e65.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e21.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eREC, REM\u0026thinsp;\u0026gt;\u0026thinsp;NREM\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003eBMI: body Mass Index, CPZ- equivalent: Chlorpromazine equivalent, GAF: Global Functioning Assessment, BPRS: Brief Psychiatric Rating Scale, CDSS: Calgary Depression Scale for Schizophrenia, IFS: Individual fitness score, REC: Recovery, REM: Remission, NREM: Non-remission\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003ePsychiatric symptoms\u003c/h3\u003e\n\u003cp\u003ePsychiatric symptoms were assessed using the BPRS and Calgary Depression Scale for Schizophrenia (CDSS) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The BPRS comprises 18 items, each scored on a scale from 1 (not present) to 7 (most severe), with a total score ranging from 18 to 126. Higher scores indicated severe psychiatric symptoms. The CDSS, which consists of nine items, was used to assess depressive symptoms in schizophrenia. Each scale ranged from 0 to 2, with higher scores indicating more severe depressive symptoms.\u003c/p\u003e\n\u003ch3\u003eEvaluation of functions\u003c/h3\u003e\n\u003cp\u003eThe GAF has been widely used to evaluate symptoms and social functioning in psychiatric illnesses [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The score ranged from 0 to 100, with a high score suggesting milder symptoms and higher functions.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eThe recovery, remission, and non-remission groups included 24, 30, and 18 patients, respectively. The Statistical Package for the Social Sciences version 27.0 was used for data analysis. The chi-square test was used for categorical variables, including sex, smoking, and marital status. The Shapiro‒Wilk test was used to analyze normality. Age, BMI, and BPRS followed a normal distribution and were analyzed using a one-way analysis of variance. Education, duration of employment, duration of illness, average daily dose, number of admissions, age at onset, GAF, CDSS, and IFS did not follow a normal distribution and were analyzed using the Kruskal‒Wallis test. The Bonferroni correction was used for post-hoc comparisons. The IFS cutoff points between the remission and non-remission groups were determined using ROC curve analysis. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003eDemographic data\u003c/h2\u003e\u003cp\u003eThe clinical characteristics and demographics of each group are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Significant differences were observed in duration of employment, duration of illness, average daily dose, and number of admissions between the groups. The duration of illness was significantly higher in the non-remission group than in the remission group; however, the duration of illness was not significantly different between the recovery and remission or non-remission groups. The average daily dose in the non-remission group was significantly higher than that in the recovery group; however, no significant difference was observed between the recovery and remission or remission and non-remission groups. The BPRS and CDSS scores of the non-remission group were significantly higher than those of the recovery and remission groups. However, no significant difference was observed between the recovery and remission groups. The GAF score in the recovery group was significantly higher than that in the remission group and significantly higher in the remission group than in the non-remission group.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eComparison of IFS between three groups\u003c/h2\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the comparison of IFS between the three groups, showing significantly higher IFS in recovery and remission groups than in the non-remission group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). In the post hoc test, the IFS was significantly higher in the recovery group than in the non-remission group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), and the IFS of the remission group was also significantly higher than that of the non-remission group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Conversely, no significant difference was observed in the IFS between the recovery and remission groups (p\u0026thinsp;=\u0026thinsp;0.86).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation between IFS and clinical characteristics\u003c/h2\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the correlation between IFS and demographic or clinical characteristics across the groups. No significant correlation was observed, except for the age of onset in the recovery group.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCorrelation between IFS and clinical characteristics among each schizophrenia group.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRecovery\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRemission\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNon-remission\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003er\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ep-Value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003er\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-Value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003er\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ep-Value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.155\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.471\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.070\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.712\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.168\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.506\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.305\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.147\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.129\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.497\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.238\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.341\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation (year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.023\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.914\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.117\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.537\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.234\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.350\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration of employment (year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.369\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.076\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.022\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.909\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.441\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.067\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration of illness (year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.937\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.092\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.628\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.371\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.129\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAverage daily dosage \u003c/p\u003e\u003cp\u003e(CPZ-equivalent, mg/day)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.131\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.543\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.011\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.954\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.049\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.846\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of admissions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.011\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.961\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.157\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.407\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.211\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.401\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at onset (year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.572\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.030\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.875\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.180\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.475\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGAF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.027\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.901\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.102\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.593\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.397\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.115\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBPRS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.195\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.361\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.094\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.623\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.194\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.441\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCDSS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.067\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.754\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.176\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.351\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.152\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.547\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eCPZ- equivalent: Chlorpromazine equivalent, GAF: Global Functioning Assessment, BPRS: Brief Psychiatric Rating Scale, CDSS: Calgary Depression Scale for Schizophrenia\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eROC analysis of remission and non-remission group\u003c/h2\u003e\u003cp\u003eBased on the ROC curve, an IFS cutoff point of 72 showed 83.3% sensitivity and 67.67% specificity, with an area under the curve of 81% (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003e This is the first study to evaluate the association between guideline adherence and the state of patients with schizophrenia. We found that the IFS in patients with schizophrenia in recovery and remission was significantly higher than that in patients with schizophrenia in non-remission. In addition, an IFS cutoff of 72 points may help distinguish between remission and non-remission pharmacotherapy. However, no significant difference in IFS was observed between the recovery and remission groups.\u003c/p\u003e\u003cp\u003e In recovery and remission patients with schizophrenia, adherence to guidelines was higher than that in non-remission patients; however, no significant difference in IFS was observed between the recovery and remission groups. This suggests that adherence to the guidelines may contribute to achieving remission in patients with schizophrenia. This study suggests that adherence to the guidelines may be effective, as indicated in previous studies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, this study uniquely evaluated the different states of schizophrenia, including recovery, remission, and non-remission. A Japanese prescription survey showed that 43% of patients received antipsychotic polypharmacy, and 85% of patients were prescribed antipsychotics and other psychotropics, including hypnotic or antianxiety medications, antidepressants, and mood stabilizers [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Another study showed that the rate of polypharmacy in Japan was higher to that in other countries [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. We considered that the number of antipsychotics or concomitant use of psychotropics might have a greater influence on the difference in IFS than the dose of antipsychotics, as the CPZ equivalent was \u0026lt;\u0026thinsp;600 mg/day across the three groups in the present study. Furthermore, this study showed that an IFS of 72 points was the cutoff for distinguishing remission and non-remission schizophrenia. Several guidelines have outlined the appropriate dose and duration of antipsychotics [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]; however, no indicator exists for the overall prescription for each patient. This result may provide a clinical target for achieving remission in non-remission patients with schizophrenia.\u003c/p\u003e\u003cp\u003eNo significant difference in IFS was observed between the recovery and remission states. Our findings showed that adherence to the guidelines was not sufficient to achieve recovery, which may indicate limitations in the guidelines for pharmacological therapy. The IFS of recovery and remission were higher than those in previous reports comparing [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], and we considered that adherence to the guidelines remained important. Conversely, the results of this study indicate that psychosocial factors are more important than pharmacotherapy for achieving recovery from remission. In fact, several psychological interventions, such as cognitive remediation, psychoeducation, social skills training, and cognitive behavioral therapy, were useful for improving social functions and preventing relapse [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Psychological interventions may need to be implemented to achieve recovery from remission.\u003c/p\u003e\u003cp\u003eThis study indicated that the IFS has two aspects in evaluating pharmacotherapy, serving as a comprehensive evaluation tool for prescriptions and therapeutic indicators. First, the JSNP guideline includes some recommendations, regarding the number of medications, dose of antipsychotics, and concomitant use of psychotropics [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and IFS could evaluate these quality indicators (QIs) simultaneously. The difference in IFS may indicate a comprehensive adherence to these QIs, and we considered that adherence to multiple QIs may contribute to achieving remission in patients with schizophrenia. However, the IFS of the recovery and remission groups also suggest that complete adherence to the guidelines may not necessarily contribute to achieving recovery or remission in patients with schizophrenia. In fact, some studies have reported the efficacy of antipsychotic polypharmacy for positive symptoms or the prevention of rehospitalization [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], and combining antipsychotics and antidepressants improved negative symptoms in patients with schizophrenia [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. While adherence to treatment guidelines is generally beneficial, some clinical situations may require individualized modifications, such as dose adjustments or selective polypharmacy, to achieve optimal outcomes. Second, the IFS could be used as a clinical indicator for pharmacotherapy. We clearly showed the cutoff points between remission and non-remission in patients with schizophrenia. Only a few biomarkers are associated with remission in patients with schizophrenia [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. This study suggests that an IFS\u0026thinsp;\u0026ge;\u0026thinsp;72 points may be an indicator of comprehensive pharmacotherapy for achieving remission in these patients. Based on these findings, we propose the \u0026ldquo;Remission criterion,\u0026rdquo; where an IFS of 72 points is the cutoff for remission in patients with schizophrenia. In the future, if various IFS cutoff points depended on the state are known, an appropriate pharmacotherapy targeting IFS for each patient with schizophrenia may be proposed. Thus, the IFS may serve not only as a tool for evaluating adherence to guidelines but also as a clinical target for pharmacotherapy across different states in patients with schizophrenia.\u003c/p\u003e\u003cp\u003eThis study has some limitations. First, the cross-sectional study design could not reveal causality between the IFS and recovery, remission, and non-remission states; longitudinal studies are needed to assess causality. Second, the sample size was relatively small, and the results should be evaluated in a larger-scale study. Third, these results were influenced by the differences in education for psychiatrists, difference of treatment approach at each institution or the trend of psychotropics prescription because this study was conducted at five psychiatric institutions in Japan.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e This study clearly showed high adherence to guidelines in patients in recovery and remission states of schizophrenia, compared with those in non-remission states, and no significant difference in IFS was observed between recovery and remission. In addition, an IFS of 72 could be a cutoff point, distinguishing between remission and non-remission. This study emphasized that adherence to guidelines is important for recovery and remission; however, psychological factors may be crucial for achieving recovery from remission. We believe that assessing IFS in long-term individual studies with large-scale samples is necessary.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBMI Body Mass Index\u003c/p\u003e\u003cp\u003eBPRS Brief Psychiatric Rating Scale\u003c/p\u003e\u003cp\u003eCDSS Calgary Depression Scale for Schizophrenia\u003c/p\u003e\u003cp\u003eCPZ Chlorpromazine\u003c/p\u003e\u003cp\u003eDSM-5 Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition\u003c/p\u003e\u003cp\u003eFGA First-Generation Antipsychotic\u003c/p\u003e\u003cp\u003eGAF Global Functioning Assessment\u003c/p\u003e\u003cp\u003eIFS Individual Fitness Score\u003c/p\u003e\u003cp\u003eJSNP Japanese Society of Neuropsychopharmacology\u003c/p\u003e\u003cp\u003eMTD Maximum Therapeutic Dose\u003c/p\u003e\u003cp\u003eQIs Quality Indicator\u003c/p\u003e\u003cp\u003eSGA Second-Generation Antipsychotic\u003c/p\u003e\u003cp\u003eTRS Treatment-Resistant Schizophrenia\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\u003cp\u003e This study was approved by the Fukuoka University Medical Ethics Review Board (approval number: U21-11-018), and all patients provided written informed consent before participation in this study. This study was conducted in accordance with to the latest version of the Declaration of Helsinki.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis work was supported by the Grant of The Clinical Research Promotion Foundation (2022).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eRA: Conceptualization, Software, Validation, Formal analysis, Investigation, Resources, Data Curation, Writing – Original Draft, Visualization, Project administration, Funding acquisition. HI: Methodology, Writing – Review \u0026amp; Editing. LG: Validation, Investigation, Writing – Review \u0026amp; Editing. KY: Data Curation. HH: Conceptualization, Methodology, Validation, Data Curation, Writing – Review \u0026amp; Editing, Supervision. All the authors have read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\u003cp\u003eThe datasets analyzed during the current study are not publicly available due to the lack of informed consent for the release of raw data but are available from the corresponding author on reasonable request.\u003c/p\u003e\u003cp\u003eCompeting interests\u003c/p\u003e\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eO'Donoghue B, Piacenza F, Plapp H, Siskind D, Lyne J. Response rates to sequential trials of antipsychotic medications according to algorithms or treatment guidelines in psychotic disorders. A systematic review and meta-analysis. 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Aust N Z J Psychiatry. 2016;50(5):410\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJapanese Society of Neuropsychopharmacology. Japanese Society of Neuropsychopharmacology: Guideline for Pharmacological Therapy of Schizophrenia. Neuropsychopharmacol Rep. 2021;41(3):266\u0026ndash;324.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eInada K, Fukumoto K, Hasegawa N, Yasuda Y, Yamada H, Hori H, et al. Development of individual fitness score for conformity of prescriptions to the Guidelines For Pharmacological Therapy of Schizophrenia. Neuropsychopharmacol Rep. 2022;42(4):502\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKodaka F, Ohi K, Yasuda Y, Fujimoto M, Yamamori H, Hasegawa N, et al. Relationships Between Adherence to Guideline Recommendations for Pharmacological Therapy Among Clinicians and Psychotic Symptoms in Patients With Schizophrenia. Int J Neuropsychopharmacol. 2023;26(8):557\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIto S, Ohi K, Yasuda Y, Fujimoto M, Yamamori H, Matsumoto J, et al. Better adherence to guidelines among psychiatrists providing pharmacological therapy is associated with longer work hours in patients with schizophrenia. Schizophrenia (Heidelb). 2023;9(1):78.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiberman RP, Kopelowicz A, Ventura J, Gutkind D. Operational criteria and factors related to recovery from schizophrenia. Int Rev Psychiatry. 2002;14(4):256\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJaaskelainen E, Juola P, Hirvonen N, McGrath JJ, Saha S, Isohanni M, et al. A systematic review and meta-analysis of recovery in schizophrenia. Schizophr Bull. 2013;39(6):1296\u0026ndash;306.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLally J, Ajnakina O, Stubbs B, Cullinane M, Murphy KC, Gaughran F, et al. Remission and recovery from first-episode psychosis in adults: systematic review and meta-analysis of long-term outcome studies. Br J Psychiatry. 2017;211(6):350\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAmerican Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5. 5th ed. American Psychiatric Pub.; 2013.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOverall JE, Gorham DR. The Brief Psychiatric Rating Scale. Psychol Rep. 1962;10(3):799\u0026ndash;812.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAndreasen NC, Carpenter WT Jr., Kane JM, Lasser RA, Marder SR, Weinberger DR. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry. 2005;162(3):441\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAddington D, Addington J, Maticka-tyndale E. Assessing Depression in Schizophrenia: The Calgary Depression Scale. Br J Psychiatry. 1993;163(S22):39\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStartup M, Jackson MC, Bendix S. The concurrent validity of the Global Assessment of Functioning (GAF). Br J Clin Psychol. 2002;41(Pt 4):417\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIchihashi K, Hori H, Hasegawa N, Yasuda Y, Yamamoto T, Tsuboi T, et al. Prescription patterns in patients with schizophrenia in Japan: First-quality indicator data from the survey of Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE) project. Neuropsychopharmacol Rep. 2020;40(3):281\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShinfuku N. Analysis of the trends of polypharmacy and high-dose prescriptions in Japan. Asia Pac Psychiatry. 2022;14(1):e12488.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMorin L, Franck N. Rehabilitation Interventions to Promote Recovery from Schizophrenia: A Systematic Review. Front Psychiatry. 2017;8:100.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evan Lochmann MWH, IntHout J, Gijsman HJ, Akdede BBK, Yagcioglu AEA, Barnes TRE, et al. Efficacy and tolerability of antipsychotic polypharmacy for schizophrenia spectrum disorders. A systematic review and meta-analysis of individual patient data. Schizophr Res. 2024;272:1\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTiihonen J, Taipale H, Mehtala J, Vattulainen P, Correll CU, Tanskanen A. Association of Antipsychotic Polypharmacy vs Monotherapy With Psychiatric Rehospitalization Among Adults With Schizophrenia. JAMA Psychiatry. 2019;76(5):499\u0026ndash;507.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGalling B, Vernon JA, Pagsberg AK, Wadhwa A, Grudnikoff E, Seidman AJ, et al. Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia. Acta Psychiatr Scand. 2018;137(3):187\u0026ndash;205.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAsada R, Hori H, Gotoh L, Yasumatsu K, Iida H, Kawasaki H. Lower plasma tumor necrosis factor-alpha is associated with symptomatic remission in patients with schizophrenia. J Psychiatr Res. 2024;177:299\u0026ndash;304.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"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},"keywords":"Guideline, Pharmacotherapy, Schizophrenia, Recovery, Remission, Non-remission","lastPublishedDoi":"10.21203/rs.3.rs-6677621/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6677621/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSeveral schizophrenia guidelines have been published, showing treatment efficacy. However, no studies have examined recovery and pharmacological therapy or guideline adherence's impact on various schizophrenia states. This study aimed to investigate adherence to pharmacological guidelines across recovery, remission, and non-remission states in patients with schizophrenia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis cross-sectional study included 72 patients with schizophrenia who met the criteria for recovery, remission, or non-remission. Adherence to pharmacological guidelines was measured using the Individual Fitness Score (IFS).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIFS was significantly higher in the recovery (88.1 ± 18.9) and remission (89.0 ± 16.7) groups than in the non-remission group (65.59 ± 21.8) (p \u0026lt; 0.01). However, no significant differences were observed between the recovery and remission groups. Receiver operating characteristic (ROC) analysis identified 72 points on the IFS as a potential cutoff point between remission and non-remission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThese results indicate that adherence to pharmacological guidelines may contribute to achieving remission from non-remission, and an IFS of 72 could be an indicator of pharmacotherapy, though it may not be enough to achieve recovery in patients with schizophrenia. Clinical practice guidelines have been developed to standardize and improve the quality of medical care, and several schizophrenia guidelines have been published worldwide. Treatments following these guidelines have been reported to be effective.\u003c/p\u003e","manuscriptTitle":"High adherence to pharmacological treatment guidelines in recovery and remission states among patients with schizophrenia: A cross-sectional study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-21 12:03:33","doi":"10.21203/rs.3.rs-6677621/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":"c0ab0cd4-f729-401a-a142-fe668f86cfbf","owner":[],"postedDate":"August 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-03T02:39:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-21 12:03:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6677621","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6677621","identity":"rs-6677621","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}