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 Cannabis use may cause psychotic symptoms, such as hallucinations and delusions, as well as persistent amotivation with reduced motivation, inactivity, and cognitive impairment. Although described as cannabis‐related amotivational syndrome, it is not recognized as an independent diagnostic entity and overlaps clinically with the negative symptoms of schizophrenia and mood disorders. We report a case of persistent amotivation following cannabis‐related psychosis that improved after electroconvulsive therapy (ECT). Case A 19‐year‐old man developed auditory hallucinations, persecutory delusions, and agitation associated with cannabis use and was admitted to a psychiatric hospital. Antipsychotic treatment improved the psychotic symptoms, but marked amotivation and inactivity, accompanied by low performance on cognitive screening, and significantly impaired daily functioning. Depressed mood and appetite loss were not evident. Although negative symptoms of schizophrenia remained a differential diagnosis, the presentation was consistent with cannabis‐related amotivational syndrome. Amantadine produced limited improvement. Following ECT, the Apathy Scale score improved from 24 to 7 and the Mini‐Mental State Examination score increased from 19 to 26, with improvements in motivation, activity, and daily functioning. Discussion This case demonstrates that clinically significant amotivation may persist after cannabis‐related psychotic symptoms improve. Persistently reduced motivation and inactivity should not be assumed to represent primary negative symptoms of schizophrenia; rather, clinicians should carefully consider mood symptoms and cannabis‐related amotivation in the differential diagnosis. This case also suggests that ECT may represent a treatment option for severe, persistent amotivation following cannabis‐related psychosis. However, because this was a single case, further validation through additional cases and long‐term follow‐up is required.
ABSTRACT Background Venlafaxine (VEN) is converted to O‐desmethylvenlafaxine (ODV) mainly through CYP2D6‐mediated O‐demethylation. However, age‐related clinical factors may also influence VEN exposure in routine practice. We examined whether age and CYP2D6 genotype show different associations with parent‐drug exposure and metabolic conversion. Methods This retrospective therapeutic drug monitoring analysis included 78 Japanese psychiatric patients with available plasma VEN and ODV concentrations and CYP2D6 genotype data. Two prespecified outcomes were analyzed without body‐weight correction: VEN concentration divided by daily dose (VEN/dose) and the ODV/VEN ratio. CYP2D6*10 and *5 were coded as reduced‐ and no‐function alleles, respectively. Log‐transformed outcomes were analyzed using regression models including age and CYP2D6 reduced/no‐function allele count. Results Nineteen patients (24.4%) were aged 65 years or older. Age was correlated with VEN/dose (Spearman rho = 0.295, p = 0.0086), and older patients had higher VEN/dose than younger patients (median, 0.522 vs. 0.192 [ng/mL]/[mg/day], p = 0.0127). In regression analysis, the incremental R 2 for age was numerically larger than that for CYP2D6 allele count for VEN/dose (incremental R 2 , 0.058 vs. 0.026). Conversely, the ODV/VEN ratio was strongly associated with CYP2D6 allele count (standardized beta = −0.391, p < 0.001; incremental R 2 = 0.145) but not with age. Age‐by‐genotype interactions were not significant for either outcome. Conclusions Age appeared to be more closely related to dose‐corrected parent VEN exposure, whereas CYP2D6 genotype predominantly determined the ODV/VEN metabolic ratio. The relative contribution of age should be interpreted descriptively because no formal comparison of effect sizes was performed. Separating exposure and metabolic‐ratio outcomes may clarify how geriatric and pharmacogenetic factors contribute to VEN disposition.
