Earlier Clozapine Offers Long-Term Benefit in Treatment-Resistant Schizophrenia

Patients with treatment-resistant schizophrenia who started clozapine earlier had significantly better Clinical Global Impression (CGI) scores at a 10-year follow-up than patients who waited the longest to start the drug, according to a study published in the Journal of Psychiatric Research.

“Our findings reinforce the need of a timely assessment of treatment-resistant criteria in early schizophrenia patients and highlight the long-term benefits of an early introduction of clozapine on those patients meeting treatment-resistant criteria,” wrote corresponding author Maria Juncal-Ruiz, MD, PhD, of the Sierrallana Hospital Department of Psychiatry, Cantabria, Spain, and coauthors.

The study was a 10-year follow-up of 218 patients with first-episode schizophrenia treated in a specialized intervention program through the Programa de Atención a Fases Iniciales de Psicosis, or Care Program for the Initial Phases of Psychosis, study. At the 10-year assessment, 16% of participants were taking clozapine, all of whom had treatment-resistant schizophrenia. The patients had tried other antipsychotics a median 1551 days before clozapine was prescribed, and the median time on clozapine was 6.3 years.

Among patients not taking clozapine at 10 years, 7.1% met criteria for treatment-resistant schizophrenia.   

Related: Scant Differences in Schizophrenia Relapse Between Antipsychotics, Meta-analysis Finds

After adjustment for baseline values, patients taking clozapine had higher CGI total scores and Scale for the Assessment of Negative Symptoms total scores at the 10-year assessment compared with patients not taking clozapine. However, when researchers looked solely at patients who met criteria for treatment-resistant schizophrenia, those prescribed clozapine had significantly lower total scores on all clinical scales compared with those not prescribed clozapine. 

Additionally, patients with treatment-resistant schizophrenia with the longest time before starting clozapine showed significantly higher CGI scores at 10 years compared with patients who initiated clozapine earlier.

Clozapine was associated with higher rates of metabolic syndrome as well as with more daytime sleepiness, sialorrhea, weight gain, fatigue, orthostatic vertigo, and constipation, according to Psychiatry Advisor coverage of the study.

References

Moreno-Sancho L, Juncal-Ruiz M, Vázquez-Bourgon J, et al. Naturalistic study on the use of clozapine in the early phases of non-affective psychosis: a 10-year follow-up study in the PAFIP-10 cohort. J Psychiatr Res. 2022;153:292-299. doi: 10.1016/j.jpsychires.2022.07.015

Nye J. Patients with first-episode schizophrenia should receive clozapine early in disease progress. Psychiatry Advisor. August 3, 2022. Accessed August 5, 2022.