Cariprazine is distinct from other antipsychotics in having high preferential affinity for the D3 receptor, which is thought to be important in modulating mood and cognition. This could help treat the negative symptoms of schizophrenia, which are poorly served by existing treatments.
Cariprazine has two equipotent metabolites contributing to its efficacy. Its long half-life of around 1 week may protect against rapid disease relapse.
The efficacy of cariprazine for the treatment of acute schizophrenia was established in three short-term, placebo-controlled trials including a total of nearly 1800 adults. One study tested fixed doses of 1.5mg, 3mg and 4.5mg cariprazine, one examined fixed doses of 3mg and 6mg cariprazine, and one evaluated fixed/flexible doses of 3—6mg and 6—9mg cariprazine.
The primary endpoint was the change from baseline to week 6 in the Positive and Negative Syndrome Scale (PANSS) total score and the secondary endpoint was the change from baseline to week 6 in the Clinical Global Impressions-Severity (CGI-S) score.
In all three studies, all doses of cariprazine showed significant improvement in both the primary and secondary endpoints compared with placebo.
In a long-term study including 765 adult patients, the efficacy of cariprazine for the prevention of relapse was investigated using time to relapse as the primary efficacy parameter. Participants were treated with cariprazine 3—9mg daily during a 20-week open-label run-in and stabilisation phase; stable patients who completed open-label treatment were then randomised on a double-blind basis to continue cariprazine (n=101) or switch to placebo (n=99) for up to 72 weeks.
Results showed that time to relapse was significantly longer in patients who remained on cariprazine than in those who were switched to placebo (p=0.001). Relapse occurred in 24.8% of cariprazine- and 47.5% of placebo-treated patients (hazard ratio 0.45, 95% CI 0.28—0.73).
A randomised, double-blind active-controlled study assessed the effect of cariprazine in 461 adults with predominantly negative symptoms of schizophrenia. The primary outcome was change from baseline to week 26 or end of treatment on the Positive and Negative Syndrome Scale factor score for negative symptoms (PANSS-FSNS).
Analysis showed that the least squares mean change in PANSS-FSNS from baseline to week 26 was significantly greater with cariprazine than risperidone (−8.90 points vs −7.44 points; least squares mean difference −1.46, 95% CI −2.39 to −0.53; p=0.0022).
Cariprazine was well tolerated in clinical trials with most adverse events being mild to moderate in severity. The most commonly reported side-effects were akathisia and parkinsonism.