This new antipsychotic was also associated with greater improvement in functioning, despite having similar effects as risperidone on positive symptoms.
Negative symptoms in schizophrenia contribute strongly to morbidity and disability and respond poorly to standard antipsychotic treatments. Also, negative symptoms can be confused with coexisting depression and with antipsychotic-induced akinesia and may sometimes improve when positive symptoms decrease. In a 26-week, randomized, controlled, manufacturer-funded, international trial, the antipsychotic cariprazine (mean dose, 4.2 mg), which has novel, potent dopamine D3 receptor activity and which was approved by the FDA in 2015, was compared with risperidone (mean dose, 3.8 mg) in 461 patients with schizophrenia.
Cariprazine showed significantly greater improvement than risperidone in negative symptoms and in personal and social functioning by week 14; differences persisted through week 26. More cariprazine recipients achieved ≥20% improvement in negative symptoms at week 26 (69% vs. 58%), yielding a clinically relevant number needed to treat of 9. The two groups did not differ in adverse events or in positive symptoms, depression, or extrapyramidal symptom change.
Although the magnitude of difference in negative symptoms seems small, cariprazine was being compared with an active, efficacious antipsychotic. In addition, the benefit was accompanied by improvements in social function and occurred in the absence of greater effects on depression and positive symptoms or reductions in extrapyramidal effects, all of which could indirectly improve negative symptoms. As the editorialists note, the effect for cariprazine when compared with a placebo would likely be much greater. The finding is consistent with cariprazine’s novel D3 receptor profile. Given the devastating personal, familial, social, and public health impact of schizophrenia, this new medication likely deserves a try in patients whose negative symptoms predominate.