Clozapine Shows Better Results in Schizoaffective Disorder

TOPLINE:

A real-world trial showed that in adults with dual psychosis, clozapine was effective in alleviating psychotic and affective symptoms, with better outcomes being observed in schizoaffective disorder (SZD) than in treatment-resistant schizophrenia (TRS).

METHODOLOGY:

• Researchers conducted a prospective, pragmatic clinical trial from 2021 to 2024 in Spain and included 127 participants with refractory psychosis (mean age, 38.5 years; 74.8% men).
• Participants were divided into three arms: those with TRS receiving clozapine (TRS-clozapine; n = 43), those with TRS receiving optimised standard antipsychotics (TRS-control; n = 42), and those with SZD receiving clozapine (SZD-clozapine; n = 42; non-randomised due to low prevalence).
• Monthly assessments over 3 months included the use of the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS), Montgomery-Åsberg Depression Rating Scale (MADRS), Calgary Depression Scale for Schizophrenia (CDSS), Clinical Global Impression (CGI) scale, and Udvalg für Kliniske Undersogelser (UKU) scale.
• Researchers evaluated the efficacy of clozapine in patients with TRS, the effect of clozapine on real-world SZD psychotic and affective symptoms, and the response and tolerability to clozapine in patients with TRS vs SZD.

TAKEAWAY:

• Compared with the TRS-control group, the TRS-clozapine group had greater 3-month reductions in PANSS positive, negative, and total (P/N/T) scores (P < .001 for all) and CDSS (P < .001), CGI (P < .001), and MADRS (P = .003) scores, whereas the SZD-clozapine group showed rapid, significant improvements in psychotic scale scores (PANSS-P, P = .027; PANSS-N, P = .002; and PANSS-T, P = .005) and YMRS, MADRS, and CDSS scores (P < .001 for all) from month 1 to month 3.
• The SZD-clozapine group showed greater reductions in the following scores than the TRS‐clozapine group at 3 months: PANSS-P (-23.4 vs -19.3), PANSS-T (-68.7 vs -63.0), YMRS (-15.3 vs -4.9), MADRS (-8.4 vs -6.0), and CDSS (-5.4 vs -4.1).
• Patients receiving clozapine reported better subjective treatment perception (P < .01) and required fewer adjunct antipsychotics and sedatives, and clozapine emerged as the sole independent predictor of superior symptom and substance use outcomes.
• Clozapine was well tolerated in both groups, with no serious treatment-related adverse events. Mild drowsiness or asthenia was observed, which was managed by lowering co-medication doses. UKU side effect scores also reduced from month 2 onwards.

IN PRACTICE:

“[The study] findings have direct clinical implications, reinforcing the evidence supporting the use of CLZ [clozapine] in dual psychosis and expanding therapeutic options for SZD,” the authors wrote. “Moving forward, efforts to improve clozapine use should focus on enhancing clinician education, standardising knowledge sources and promoting best practices in its management. Additionally, the development of well-designed long-term studies will be essential,” they added.

SOURCE:

This study was led by Marc Peraire, Consorci Hospitalari Provincial de Castelló, Castellón de la Plana, Spain. It was published online on August 1 in the Journal of Psychopharmacology.

LIMITATIONS:

This study was limited by incomplete patient histories and the absence of antisuicidal efficacy measures. Additional constraints were the lack of comparison between dual-disorder and pure psychosis cohorts, unstable diagnostic labels, gender imbalance, a single-site design, potential overfitting in regression models, and a relatively short follow-up period.

DISCLOSURES:

This study received financial support from the Research Foundation of the Provincial Hospital of Castellón. The authors reported having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.