Better adherence to guidelines among psychiatrists providing pharmacological therapy is associated with longer work hours in patients with schizophrenia

Schizophrenia is frequently accompanied by social dysfunctions such as social withdrawal, impaired social cognition, social anxiety, and deficits in social skills, which can impede employment and reduce work hours. Pharmacological therapy with antipsychotics is central to symptom management, though side effects and common polypharmacy practices can affect functioning. Clinical guidelines (e.g., American Psychiatric Association, NICE, and Japanese Society of Neuropsychopharmacology) recommend antipsychotic monotherapy and minimizing adjunctive medications. The Effectiveness of Guideline for Dissemination and Education in psychiatric treatment (EGUIDE) project in Japan aims to enhance adherence to these guidelines. The authors developed an Individual Fitness Score (IFS) to quantify how closely psychiatrists’ prescriptions align with guideline recommendations for each patient. Prior work links guideline-concordant care to improved quality of life and milder symptoms, but its relationship to social functional outcomes like work hours was unclear. The study’s hypothesis was that higher IFS (better adherence) would be associated with longer work hours in patients with schizophrenia.

The paper reviews that antipsychotics are the foundation of schizophrenia treatment, mainly improving positive symptoms and to a lesser degree negative symptoms, cognition, and social functioning. Polypharmacy is common in practice despite limited evidence and increased side-effect burden, prompting guidelines to emphasize monotherapy and caution with adjunctive agents (anticholinergics, benzodiazepines, antidepressants, mood stabilizers). National and international guidelines (APA, NICE, Japanese) advocate monotherapy and minimal polypharmacy; Japanese guidelines also recommend avoiding unnecessary adjuncts. The EGUIDE project in Japan promotes guideline dissemination and adherence. To assess real-world adherence, the authors previously developed the Individual Fitness Score (IFS), a composite measure (0–100) of prescription conformity to guidelines, with separate algorithms for TRS and non-TRS. Prior studies have shown that adherence to schizophrenia treatment guidelines is associated with better quality of life, fewer symptoms, and that specific pharmacotherapy choices (e.g., switching from polypharmacy to monotherapy; clozapine in TRS) can improve functioning and employment. However, the direct link between comprehensive guideline adherence (IFS) and social outcomes such as work hours had not been established.

Design: Cross-sectional observational study. Participants: 286 inpatients and outpatients with schizophrenia recruited at Osaka University Hospital, overlapping with prior cohorts. Diagnosis was confirmed by at least two trained psychiatrists using DSM-IV criteria via the Structured Clinical Interview for DSM-IV (SCID). Patients were categorized as treatment-resistant schizophrenia (TRS) or non-TRS. TRS was defined per Japanese criteria: failure to achieve GAF ≥41 despite at least two adequate antipsychotic trials (chlorpromazine equivalent ≥600 mg/day; at least one atypical; ≥4 weeks each), corroborated by clozapine use or electroconvulsive therapy (ECT) history and documented poor response. Measures: Guideline adherence was quantified by the Individual Fitness Score (IFS) for schizophrenia (range 0–100; higher indicates better adherence). Separate scoring formulas were used for TRS and non-TRS. For non-TRS, 100 points indicates antipsychotic monotherapy without unnecessary adjuncts; for TRS, 100 points indicates clozapine use or ECT; points are deducted for additional antipsychotics and psychotropics. Work hours were assessed using the Social Activity Assessment (SAA), comprising “work for pay,” “work at home,” and “student” sections. Trained psychologists/physicians interviewed patients about the preceding 12 weeks; weekly hours (hr/week) were averaged over 12 weeks and summed across sections. Statistical analysis: Normality was assessed by Kolmogorov–Smirnov tests; given non-normal distributions, nonparametric analyses were used. The association between IFS and work hours was tested with Spearman’s rank correlation (two-tailed alpha < 0.05). Additional exploratory linear regressions examined the relationship including TRS diagnosis as a covariate and adjusting for potential confounders (age, sex, education, age at onset, illness duration, symptom severity). Ethics: Approved by the National Center of Neurology and Psychiatry (A2018-095) and Osaka University (706-11). Written informed consent obtained.

- Sample characteristics (n=286): Mean IFS 52.6 ± 39.1 (range 0–100). Mean work hours 10.7 ± 16.3 hr/week (range 0–82). - Primary association: Higher IFS was significantly correlated with longer work hours (Spearman rho = 0.18, p = 2.15 × 10^-3). - TRS vs non-TRS: 40 TRS (14.0%) and 246 non-TRS. Most TRS patients (34/40, 85.0%) did not work at all; TRS work hours: 1.1 ± 3.4 hr/week (range 0–15). Non-TRS work hours: 12.2 ± 17.0 hr/week (range 0–82). - Non-TRS subset: The positive correlation remained significant after excluding TRS (rho = 0.19, p = 3.32 × 10^-3). - Regression including TRS status: In all patients, the relationship between work hours and IFS remained significant when including TRS diagnosis as a covariate (beta = 0.16, p = 4.74 × 10^-3). - Sensitivity to confounders: The association between IFS and work hours remained significant after adjusting for age, sex, education, age at onset, duration of illness, and symptom severity (p < 0.05), except when adjusting for negative symptoms, where it was attenuated (beta = 0.054, p = 0.064).

The study demonstrates that better adherence to pharmacological treatment guidelines, as captured by the comprehensive IFS metric, is associated with greater work participation (longer weekly hours) among patients with schizophrenia. This supports the hypothesis that guideline-concordant prescribing—emphasizing antipsychotic monotherapy, appropriate use of clozapine/ECT in TRS, and minimization of adjunctive psychotropics—relates to improved social functioning. While TRS patients generally had minimal work engagement, the IFS–work hours association persisted both within the non-TRS subgroup and in the full sample after accounting for TRS status, suggesting the relationship is not solely driven by TRS/non-TRS differences. The findings align with prior evidence that monotherapy and appropriate TRS treatments can improve functioning and quality of life, extending these observations to a composite adherence index and a concrete social outcome (work hours). The persistence of the association after adjusting for multiple demographic and clinical covariates indicates robustness, though negative symptom severity may partially mediate or confound the relationship. Overall, enhancing psychiatrists’ adherence to guidelines (e.g., through dissemination and education initiatives like EGUIDE) may help improve functional outcomes, including employment-related activity, in schizophrenia.

Better comprehensive adherence to pharmacological guidelines by psychiatrists, measured via the IFS, is associated with longer work hours among patients with schizophrenia. This relationship holds after excluding TRS cases and after adjusting for TRS status and several confounders, suggesting a potentially generalizable link between guideline-concordant prescribing and social functioning. The study highlights the potential value of widespread education and training to improve guideline adherence in clinical practice. Future research should employ longitudinal designs, incorporate detailed treatment histories and social context variables, examine the roles of psychosocial interventions and family support, and explore domain-specific work activities (paid work, housework, student) to clarify causal pathways and mediators (e.g., negative symptoms, cognition).

- Cross-sectional design precludes causal inference between guideline adherence and work hours. - IFS was calculated from prescriptions at a single time point; duration of stable treatment, prior medication history, and treatment response trajectories were not captured. - Lack of detailed social background information, which may confound work outcomes. - No data on psychosocial interventions or family support, both of which can influence employment. - Cognitive dysfunction and psychiatric symptoms may mediate the relationship but were not fully modeled; negative symptoms, in particular, attenuated the association in adjusted analyses. - Work hours were aggregated across SAA domains (paid work, housework, student); differing skill demands may warrant domain-specific analyses. - Japanese prescribing regulations limit clozapine combination therapy, influencing guideline recommendations and IFS scoring; updates to systems/guidelines may necessitate revising IFS computation. - TRS definition followed Japanese criteria; international consensus criteria may differ.