Amisulpride Linked to Improved Schizophrenia Scores at 52 Weeks

Prof. Erik Johnsen

First-line atypical antipsychotic drug amisulpride is associated with better outcomes in patients with schizophrenia over 52 weeks than comparators aripiprazole and olanzapine, according to new findings.

In a new head-to-head, pragmatic assessment of the 3 antipsychotic therapies, a team of Norwegian investigators reported findings indicating minimal safety difference, yet significant long-term benefits of the agents among adults with schizophrenia-spectrum disorders and active psychosis.

The believed mechanism of amisulpride is in its antagonizing of the dopamine D2 receptor. It is currently indicated in the US for the prevention of postoperative nausea and vomiting as both a lone or combining therapy.

Led by Professor Erik Johnsen, of the Division of Psychiatry at Haukeland University, the team provided a first-of-its-kind assessment of the first-line antipsychotic therapies in one-year schizophrenia care.

Johnsen and colleagues conducted the rater-blind, randomized controlled trial throughout 3 academic psychiatric centers in Norway, as well as another in Austria. Enrolled patients were ≥18 years old, with ICD-10 criteria met for schizophrenia-spectrum disorders as well as active psychosis symptoms.

The 144 eligible patients treated between October 2011 and December 2016 were randomly assigned 1:1:1 to either amisulpride (n = 44), aripiprazole (n = 48), or olanzapine (n = 52). Allocation of therapy, as well as starting dose and treatment adjustments, were open to patients and staffs and left to the discretion of the treating clinician.

Investigators followed up with patients at 52 weeks post-assignment, with a primary outcome analysis of reduction in Positive And Negative Syndrome Scale (PANSS) total score at that time. Mean patient PANSS score at baseline was 78.4 (SD, 1.4).

At the study endpoint, patients treated with amisulpride had a total PANSS score reduction of 32.7 points (SD, 3.1), versus 21.9 among patients with aripiprazole (SD, 3.9; P = .027) and 23.3 points with olanzapine (SD, 2.9; P = .025).

The team observed 26 serious adverse events (SAEs) among 20 patients—primarily among the patients treated with aripiprazole and olanzapine (16 [75%]). Investigators also reported one patient death by suicide, one unspecified death, and one-life threatening accident during follow-up, after the treatment periods had ended.

Mean weight gain, as well as increased in serum lipids and prolactin, were observed across all treatment groups.

Johnsen and colleagues concluded amisulpride provided more efficacy than 2 competitors in reducing PANSS total scores over 1 year among adults with schizophrenia-spectrum disorders, with generally minimal difference in adverse events.

“This study supports the notion that clinically relevant efficacy differences exist between antipsychotic drugs,” they wrote. “Future research should aim to compare first-line antipsychotics directly in pragmatic clinical trials that reflect everyday clinical practice.”

The study, “Amisulpride, aripiprazole, and olanzapine in patients with schizophrenia-spectrum disorders (BeSt InTro): a pragmatic, rater-blind, semi-randomised trial,” was published online in The Lancet Psychiatry.