Randomised controlled trial of clozapine in resistant schizophrenia and schizoaffective disorder.

BACKGROUND

Clozapine (CLZ) stands out for its unique receptor profile, making it more effective than other antipsychotics, especially in treatment-resistant schizophrenia (TRS). There is growing evidence supporting its use in schizoaffective disorder (SZD), although diagnostic challenges and drug characteristics have complicated the implementation of specific clinical trials.

AIM: Compare efficacy and tolerability of CLZ in real-world patients with TRS and SZD.

METHODS

Prospective, pragmatic, three-month, evaluator-blinded clinical trial with two randomised controlled arms (TRS groups) and a third fixed arm (SZD group). The clinical response was assessed by monthly visits during which the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale (MADRS), Calgary Depression Scale for Schizophrenia (CDSS), Clinical Global Impression (CGI) and Udvalg für Kliniske Undersogelser were administered. One hundred twenty-seven participants (74.8% men, 25.2% women; 84 TRS, 42 SZD; mean age of 38.53) completed the follow-up.

RESULTS

Patients treated with CLZ showed a greater reduction in all the PANSS subscales, MADRS and CDSS. In cases of SZD, there was a significant decrease in positive (F: 3.72, p < 0.05) and negative (F: 6.58, p < 0.01) symptoms, the overall score of PANSS (F: 5.64, p < 0.01) and YMRS (F: 12.01, p < 0.01). Patients using CLZ had a better subjective perception of their treatment (χ2: 17.29, p < 0.01). CLZ prescription was the only predictor of better outcomes across all the scales and improved substance use (dual disorders).

CONCLUSIONS

CLZ was effective in reducing psychotic and affective symptoms in patients with dual psychosis, with better outcomes in SZD compared with TRS.EudraCT protocol trial:2021-001278-44 (Comparative analysis of the effectiveness of clozapine in resistant schizophrenia and schizoaffective disorder; clinicaltrialsregister.eu/ctr-search/trial/2021-001278-44/ES).