Further evidence that antipsychotic medication does not prevent long-term psychosis in higher-risk individuals

Although existing guidelines have discouraged use of antipsychotics for general clinical high-risk (CHR) individuals, it is unclear if antipsychotics can prevent psychosis in higher-risk population. We aimed to study the comparative real-world effectiveness of antipsychotic treatments for preventing psychosis in higher-risk CHR individuals.

A total of 300 CHR individuals were identified using the structured interview for prodromal syndromes (SIPS) and followed the participants for 3 years. In total, 228(76.0%) individuals completed baseline assessments using the NAPLS-2 risk calculator (NAPLS-2-RC), and 210(92.1%) completed the follow-up. The sample was further stratified according to risk level. "Higher-risk" was defined based on the NAPLS-2-RC risk score (≥ 20%) and SIPS positive symptom total scores (≥ 10). The main outcome was conversion to psychosis and poor functional outcomes, defined as a global assessment of function (GAF) score lower than 60 at follow-up.

In higher-risk CHR individuals, we found no significant difference in the rate of conversion to psychosis or poor functional outcomes between the antipsychotic and no-antipsychotic groups. Low-risk individuals treated with antipsychotic drugs were more likely exhibit poor functional outcomes compared with the no-antipsychotics group(NAPLS-2-RC estimated risk: χ² = 8.330, p = 0.004; Positive symptom severity: χ² = 12.997, p < 0.001). No significant effective factors were identified for prevention of the conversion to psychosis; conversely, CHR individuals who were treated with high dose antipsychotics (olanzapine, aripiprazole) showed a significantly increased risk of poor functional outcomes.

In CHR individuals, antipsychotic treatment should be provided with caution because of the risk of poor functional outcomes. Further, antipsychotic treatment does not appear to prevent onset of psychosis in real-world settings.