BACKGROUND The Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project is a nationwide Japanese educational program promoting guideline-concordant pharmacotherapy for schizophrenia and major depressive disorder (MDD). Psychiatrists' self-reported clinical behavior (CB) scores after EGUIDE training are partially associated with objective quality indicators of specific practices. However, their association with comprehensive objective measures of overall guideline adherence remains unclear. METHODS This multicenter observational study included 1897 EGUIDE-trained psychiatrists. CB was assessed online immediately after training. The Guideline Adherence Rate (GAR) was calculated for 5328 patients with schizophrenia and 3538 patients with MDD whose discharge records were linked to their psychiatrist's CB score. Associations were evaluated using unadjusted patient-level Spearman correlations, without modeling clustering within psychiatrists or institutions. Sensitivity analyses aggregated the data to the psychiatrist-year level, adjusted for institution type, psychiatrist experience, and patient age, and used generalized estimating equations (GEE) to correct the patient-level inference for clustering. RESULTS CB scores showed positive but very weak correlations with GAR (schizophrenia, ρ = 0.09-0.14; MDD, ρ = 0.08-0.11; all p < 0.001). Squared coefficients (approximately 0.006-0.020) indicated that CB scores accounted for < 2% of the rank-order variation in GAR. These associations remained statistically significant in psychiatrist-year-level, covariate-adjusted, and clustering-corrected (GEE) sensitivity analyses. CONCLUSIONS Post-training self-reported CB scores were weakly associated with patient-level GAR. Given the cross-sectional, unadjusted analysis and the non-independence of patients treated by the same psychiatrist, these findings do not establish CB as a reliable proxy for actual clinical practice. TRIAL REGISTRATION University Hospital Medical Information Network Clinical Trials Registry, UMIN000022645.
BACKGROUND This study investigated pharmacotherapy treatment patterns, focusing on atypical antipsychotics (AAP) augmentation therapy, in patients with major depressive disorder (MDD) who initiated antidepressant monotherapy in Japan. METHODS This retrospective cohort study was conducted using a large Japanese claims database. Patients with MDD aged ≥ 18 years who were subsequently prescribed antidepressants between June 2013 and June 2020 were enrolled. We identified patients who initiated antidepressant monotherapy as the first line of treatment (LOT1). Treatment patterns, including the number, duration, and sequence of LOTs, were examined before and after AAP augmentation therapy. RESULTS In total, 50 355 patients received antidepressant monotherapy in LOT1; the most common therapy was selective serotonin reuptake inhibitors (SSRIs). The use of AAP augmentation therapy increased with progression of LOTs. Overall, 3811 patients (7.6%) received AAP augmentation therapy after a mean of 1.4 LOTs and 270 days from treatment initiation. Although 37.9% of these patients changed to other treatments in the next LOT within 180 days, 46.4% continued AAP augmentation therapy for ≥ 180 days. Among patients receiving antidepressant monotherapy in LOT1, 14.6% underwent ≥ 3 LOTs and the most common treatment pattern was SSRI-SSRI-SSRI. CONCLUSIONS The proportion of patients receiving AAP augmentation therapy was low. Although few LOTs were required before AAP augmentation therapy, the claims-defined interval before AAP augmentation therapy was relatively long. Approximately half of the patients demonstrated prescription persistence with AAP augmentation therapy for ≥ 180 days. These findings may help clinicians refine treatment strategies regarding the timing of AAP augmentation, providing a basis for future research on how such adjustments might influence therapeutic outcomes in MDD.
ABSTRACT Background Insomnia disorder affects approximately 10% of people. The persistence of insomnia, despite treatment, remains high. Cannabis‐based medicinal products (CBMPs) have been proposed as a potential treatment for insomnia. This study aims to use data from the UK Medical Cannabis Registry to analyze changes in self‐reported sleep quality in patients prescribed CBMPs for insomnia. Methods A prospective cohort study of patients treated with CBMPs for insomnia was completed. The primary outcome was the Single‐Item Sleep Quality Scale (SQS). This was assessed at baseline and at 1, 3, 6, 12, 18, and 24 months from baseline. Secondary outcomes included change in anxiety and general health‐related quality of life. p ‐values < 0.050 were considered statistically significant. Results Two hundred and eleven participants met the inclusion criteria. Over half ( n = 126; 59.72%) were users of cannabis at baseline. At the primary endpoint of 24 months, mean SQS improved from 2.46 ± 2.10 (mean ± standard deviation (SD)) at baseline to 5.14 ± 2.75 (mean difference +2.68; 95% confidence interval (CI) 2.23–3.14; p < 0.001), with improvements observed at all timepoints. SQS values of 0 (odds ratio (OR) 15.49; 95% CI 3.87–65.19; p < 0.001) and 1–3 (OR 4.90; 95% CI 1.87–13.80; p = 0.002) at baseline and prescription of dried flower CBMPs (OR 4.99; 95% CI 1.27–21.39; p = 0.025) were associated with clinically significant improvements in sleep quality at 24 months. Seventeen participants (8.06%) reported adverse events. Participants aged over 60 were more likely to report an adverse event (OR 19.08; 95% CI 1.52–535.75; p = 0.036). Conclusion Initiation of CBMPs was associated with improvements in self‐reported sleep quality across 2 years, with the largest associations observed in those with the most severe impairment. As an uncontrolled, observational study of a self‐selected and predominantly cannabis‐experienced cohort, placebo effects, regression to the mean, and selection bias cannot be excluded.
ABSTRACT The therapeutic effects of antipsychotic drugs are primarily achieved through dopamine D2 receptor antagonism. However, excessive striatal D2 receptor blockade is associated with extrapyramidal side effects (EPS) in schizophrenic patients. Clinical studies indicate a therapeutic window of approximately 60%–80% striatal D2 receptor occupancy, with higher occupancy increasing the risk of EPS. However, conventional rodent dosing paradigms rarely maintain clinically comparable receptor occupancy, limiting their translational relevance. Here, we investigated whether continuous antipsychotic administration designed to achieve clinically relevant striatal D2 receptor occupancy can be used to evaluate extrapyramidal motor liability in mice. Using an occupancy‐guided dosing paradigm, we continuously administered haloperidol or olanzapine and assessed catalepsy as an index of EPS. To validate catalepsy as an EPS‐like phenotype, we examined whether it could be attenuated by an anticholinergic agent, consistent with the clinical management of EPS. Catalepsy was observed only under high‐occupancy haloperidol condition. A significant increase in catalepsy time was observed only in mice receiving haloperidol at a dose producing approximately 90% D2 receptor occupancy on day 3, whereas no catalepsy was detected under lower occupancy conditions with either haloperidol or olanzapine. Importantly, haloperidol‐induced catalepsy was significantly attenuated by scopolamine. Together, these findings demonstrate that an occupancy‐guided continuous antipsychotic dosing paradigm enables evaluation of EPS‐like behavior under clinically relevant D2 receptor occupancy conditions in mice, providing a translational framework linking clinical PET studies with preclinical research.
ABSTRACT Aims Although combining long‐acting injectable antipsychotics (LAIs) with psychosocial treatments for schizophrenia is important, psychiatrists' attitudes toward this approach remain underexplored. We investigated Japanese psychiatrists' perceptions of combining atypical LAIs with psychosocial interventions. Methods An anonymous cross‐sectional web‐based survey was administered to 1038 mid‐career Japanese psychiatrists, of whom 69 provided complete responses. Participants' general attitude toward recommending atypical LAIs was dichotomized as positive or negative/neutral, and they rated on a 4‐point scale the usefulness of combining atypical LAIs with five psychosocial interventions: (1) psychosocial treatment (e.g., psychoeducation), (2) day/night care, (3) community care, (4) financial/employment support, and (5) housing support. Results Thirty‐nine respondents held a positive attitude toward recommending atypical LAIs, whereas 30 held a negative/neutral attitude. A positive attitude was significantly associated with perceiving the combination as useful for psychosocial treatment ( p = 0.038), financial/employment support ( p = 0.015), and housing support ( p = 0.041), but not for day/night care ( p = 0.090) or community care ( p = 0.079). Free‐text rationales most commonly cited improved adherence and relapse prevention, enhanced illness insight, and synergistic effects as reasons for valuing the combination. Conclusions This exploratory study suggests that mid‐career Japanese psychiatrists, particularly those with a favorable attitude toward atypical LAIs, perceive the combination of LAIs with psychosocial support not merely as an adherence tool but as a synergistic strategy promoting broader functional recovery. Because respondents represent a small, predominantly male, self‐selected sample, the generalizability of the findings is limited.
