Antipsychotics range in efficacy for treatment of schizophrenia spectrum disorder

Key takeaways:

• Paliperidone 3-month LAI, aripiprazole LAI, olanzapine LAI and clozapine fared similarly to commonly used oral olanzapine, researchers found.
• Quetiapine was associated with the highest risk for relapse.

Antipsychotics differed in their efficacy in preventing relapse hospitalization and treatment failure among patients with schizophrenia spectrum disorder, according to research published in JAMA Network Open.

“Aside from clozapine [...] randomized clinical trials (RCTs) have not distinguished large differences in relapse prevention among antipsychotics, and disagreement exists as to which agents, if any, should be prioritized,” Aleksi Hamina, PhD, a researcher in the department of forensic psychiatry at the University of Eastern Finland Niuvanniemi Hospital, and colleagues wrote.

This inspired the researchers to perform a population-based comparative effectiveness research study with a within-individual design of different antipsychotics, including recently approved agents, and their ability to prevent relapse and treatment failure among patients with schizophrenia spectrum disorder compared with oral olanzapine, the most commonly used antipsychotic.

They used several Swedish health and population registers to analyze data of 131,476 patients aged 16 to 65 years (53.3% men; mean age, 45.7 years ± 16.2 years) who were diagnosed with schizophrenia spectrum disorder from 2006 to 2021.

The researchers determined antipsychotic use using the National Prescribed Drug Register. They defined relapse as hospitalization due to psychosis and treatment failure as a composite of psychiatric hospitalization, death or any change in antipsychotic medication (switch, discontinuation or additional antipsychotics), with both outcomes adjusted for time-invariant factors, including temporal order of treatments, time since cohort entry and concomitant psychotropic drugs.

Results showed the most frequently used oral antipsychotics were olanzapine, risperidone and aripiprazole and the most frequent long-acting injectables (LAIs) were zuclopenthixol LAI, perphenazine LAI and risperidone LAI.

During a median follow-up of 12 years, 63,730 (48.5%) patients experienced a psychotic relapse at least once.

Compared with oral olanzapine, the best-ranked antipsychotics for relapse prevention were paliperidone 3-month LAI (adjusted HR = 0.66; 95% CI, 0.51-0.86), aripiprazole LAI (aHR = 0.77; 95% CI, 0.7-0.84), olanzapine LAI (aHR = 0.79; 95% CI, 0.73-0.86) and clozapine (aHR = 0.82; 95% CI, 0.79-0.86), followed by other LAIs, including paliperidone 1-month LAI (aHR = 0.9; 95% CI, 0.84-0.96).

Notably, quetiapine was associated with the highest risk for relapse (aHR = 1.44; 95% CI, 1.38-1.51), which lowered after a post-hoc analysis removed small-dose use, although the risk remained “remarkably” high (aHR = 1.29; 95% CI, 1.23-1.36), according to the researchers.

Further, 93,464 (71.1%) patients experienced treatment failure at least once. Paliperidone 3-month LAI (aHR = 0.36; 95% CI, 0.31-0.42), aripiprazole LAI (aHR = 0.6; 95% CI, 0.57-0.63), olanzapine LAI (aHR = 0.67; 95% CI, 0.63-0.72) and paliperidone 1-month LAI (aHR = 0.71; 95% CI, 0.68-0.74) were associated with the lowest risk for treatment failure compared with oral olanzapine.

The researchers noted these findings were largely similar between men and women.

Additionally, a meta-analysis showed LAIs were associated with a lower risk for relapse compared with their oral counterparts (aHR = 0.81; 95% CI, 0.79-0.84).

There were several limitations to this study, the researchers noted, including the possibility of residual confounding and the underreporting of some covariates like substance abuse disorders.

“For both outcomes, especially paliperidone 3-month LAI, aripiprazole LAI, olanzapine LAI and clozapine fared well in comparison with the most commonly used antipsychotic, oral olanzapine. In contrast, quetiapine systematically performed worse than other antipsychotics,” Hamina and colleagues wrote.

These findings suggest that it may be beneficial to initiate treatment for patients with schizophrenia spectrum disorder with the most effective oral and LAI antipsychotics, according to the researchers.