Background: Treatment-resistant schizophrenia (TRS), which affects about one-third of patients with schizophrenia, remains a major challenge in psychiatric treatment. Although clozapine is the gold standard therapy for TRS, its adverse effect profile has led to growing interest in alternatives such as high-dose olanzapine (HDO), whose clinical utility remains under scrutiny. Methods: PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials comparing HDO versus clozapine for TRS. Statistical analysis was carried out using R software. Outcomes of interest included the Clinical Global Impressions Scale and the Positive and Negative Syndrome Scale (PANSS), as well as incidence rates of adverse effects. Mean differences and relative risk with P values <0.05 were considered statistically significant. Results: Five studies and 469 patients, of which 236 (50.3%) received HDO, were included. The follow-up periods ranged from 14 to 24 weeks. No statistically significant differences were observed between the HDO and clozapine groups on the Clinical Global Impressions Scale or the PANSS Positive score. In contrast, HDO use was significantly associated with improvements in PANSS Negative scores. Moreover, incidences of the adverse events hypersalivation and postural hypotension were significantly higher in the clozapine group. The incidence of weight gain was similar in the 2 groups. Conclusions: While this meta-analysis revealed no significant difference in efficacy between clozapine and HDO for most outcomes, HDO did show a significant efficacy advantage over clozapine in the treatment of negative symptoms in adults with TRS. Adverse events were more frequently reported in the clozapine group, suggesting a more favorable safety profile for HDO. These results support HDO as a viable and potentially safer alternative to clozapine in the management of TRS.
Kotochinsky et al. (Sun,) studied this question.
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