No studies have compared clinical outcomes after discontinuation of clozapine between patients who responded to clozapine and those who did not. Therefore, we examined 1-year clinical outcomes after clozapine discontinuation in responders and nonresponders. We reviewed data on patients who discontinued clozapine and retrospectively followed them for 1 year. Clinical information was collected from medical records starting at the initiation of clozapine administration, at discontinuation and at 1 year after discontinuation. In addition, clinical status was assessed using the Clinical Global Impression -Severity (CGI-S) and Clinical Global Impression -Improvement (CGI-I) scales. We classified the patients into clozapine responder and nonresponder groups according to the CGI-I score. Thirty-nine patients were enrolled in this study. Olanzapine was the most common antipsychotic prescribed after clozapine discontinuation in both the responder and nonresponder groups. The mean CGI-S score significantly increased 1 year after clozapine discontinuation in the responder group and significantly decreased in the nonresponder group; there was a significant difference in changes in the CGI-S scores between the groups. The difference remained significant after controlling for clozapine dose and duration of treatment. The findings suggest that clinicians may consider continuing and discontinuing clozapine treatment for patients who responded to clozapine and those who did not, respectively.

BackgroundRecent studies have highlighted the clinical usefulness of near-infrared spectroscopy (NIRS) in psychiatry. However, the potential effects of psychotropics on NIRS signals remain unknown.MethodsWe conducted a systematic chart review of 40 depressed patients who underwent NIRS scans during a verbal fluency task to clarify the relationships between psychotropic dosage and NIRS signals. The dosage of psychotropic medications was calculated using defined daily dose (DDD). We investigated the associations between the DDD of psychotropic medications and oxygenated hemoglobin (oxy-Hb) in single channel levels.LimitationsRetrospective study design and small sample size are the main limitations.ResultsMultiple regression analysis revealed that one channel in the right temporoparietal region had a significant association with antidepressant DDD controlling for age, sex, depression severity, and the DDD of antipsychotics and benzodiazepines. Moreover, high doses of antidepressants had significant effects on NIRS signals compared with low doses, in group comparisons.ConclusionsThe dose-dependent impact of antidepressants on NIRS signals should be taken into account when interpreting NIRS data.

Introduction Clozapine is the gold standard of treatment for patients with treatment-resistant schizophrenia. However, approximately 60% of those patients do not respond to clozapine; moreover, clinical outcomes after clozapine discontinuation are unclear so far. Therefore, we conducted a systematic review to clarify the outcomes after clozapine discontinuation. Methods A systematic literature search was conducted, using MEDLINE and Embase with the following keywords: (clozapine AND (cessation* OR cease* OR withdraw* OR discontinu* OR halt* OR stop* OR switch*) AND (schizophreni* OR schizoaffective)). Results A total of 28 clinical studies from 27 articles were identified and included in this systematic review. Three randomized controlled trials reported worsening of psychiatric symptoms. In 10 single-arm studies, the results of worsening and improving psychiatric symptoms were inconsistent. In one large retrospective cohort study, clozapine rechallenge, olanzapine, and antipsychotic polypharmacy had lower rehospitalization rates compared to no medication after clozapine discontinuation. In the other 14 retrospective studies, the vast majority showed worsening of clinical status after clozapine discontinuation. Among five studies on clinical outcomes after clozapine rechallenge, four reported improvements in clinical status in more than half of patients who rechallenged clozapine. The remaining study reported that the clozapine discontinuation-rechallenge group had a worse remission assessment score than the clozapine discontinuation-no rechallenge group. Discussion Clinical outcomes generally worsen after clozapine discontinuation. Clozapine rechallenge and olanzapine may be considered following clozapine discontinuation. The outcomes after clozapine discontinuation in clozapine non-responders remain inconclusive; therefore, well-designed studies are warranted.

Purpose Mirror-image studies, which compare equal periods of time before and after a new treatment is introduced, may reflect the real-world impact of that treatment. However, most mirror-image studies that have investigated the impact of long-acting injectable antipsychotics (LAIs) were unidirectional in design, for patients switching from oral antipsychotics (OAPs) to LAIs. Therefore, we conducted a bidirectional mirror-image study comparing LAIs and OAPs. Methods We included 126 schizophrenia or schizoaffective disorder patients' LAI treatment data from 3 psychiatric hospitals. Patients took OAPs for 6 months or more before initiating LAIs, or the reverse. We obtained data on the number of hospitalizations as a primary outcome, plus the total duration and mean duration of hospitalization as secondary outcomes during the 6 months of the patients' first treatment, and the 6 months after the patients started their second type of treatment. Results The results indicated that there was no significant difference in any outcomes between LAI and OAP treatment when going from LAIs to OAPs (n = 59). However, when patients started with OAPs and switched to LAIs (n = 67), they were hospitalized a significantly fewer number of times, and the duration of their stays was shorter in the LAI phase than in the OAP phase. When combined with bidirectional data, LAI superiority was still observed. Conclusions The findings endorse the relative effectiveness of LAIs over OAPs in the real world, although the inherent flaws of mirror-image studies such as expectation bias and having no parallel comparator should be considered.