Adjunctive pimavanserin may improve negative schizophrenia symptoms
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Adjunctive pimavanserin significantly improved outcomes among patients with predominant negative symptoms of schizophrenia, according to data presented at the American Society of Clinical Psychopharmacology Annual Meeting.
“Negative symptoms are among the most urgent and major unmet treatment needs in schizophrenia,” Henry Nasrallah, MD, director of the neuropsychiatry and schizophrenia programs at University of Cincinnati College of Medicine, told Healio Psychiatry. “Negative symptoms are highly disabling, causing social and vocational dysfunction in 50% to 60% of patients with schizophrenia. Despite many attempts, no effective treatment has been discovered for negative symptoms, so it is quite exciting to have the possibility of the novel psychotropic medication, pimavanserin, showing efficacy in negative symptoms.”
The FDA approved the inverse agonist/antagonist pimavanserin (Nuplazid, Acadia) as an atypical antipsychotic for the treatment of delusions and hallucinations associated with Parkinson’s disease psychosis. In the current poster session, Nasrallah and colleagues presented results of the phase 2 ADVANCE study, which evaluated adjunctive pimavanserin’s effects on negative symptoms of schizophrenia. The 26-week, randomized, double-blind, placebo-controlled study included 403 stable outpatients with schizophrenia who had predominant negative symptoms. Key inclusion criteria were schizophrenia diagnosis for 1 year or longer and a score of 20 or greater on the sum of the seven Positive and Negative Syndrome Scale (PANSS) Marder negative factor items at screening and baseline. The researchers analyzed the change from baseline in Negative Symptom Assessment-16 (NSA-16) total score using mixed model repeated measure analysis.
Patient demographics and characteristics were similar between the 172 pimavanserin recipients and 201 placebo recipients who completed the study and were included in the efficacy analysis. Mean patient age was 37.2 years, and 87.8% were from European sites.
Results showed a significant improvement in mean NSA-16 total score from baseline to 26 weeks among patients who received pimavanserin vs. placebo; however, the researchers observed no significant difference between the groups in change in Personal and Social Performance Scale score from baseline to 26 weeks. Final pimavanserin doses were 34 mg for 107 patients, 20 mg for 89 patients and 10 mg for three patients. Among those who received the 34 mg dose at 26 weeks, the change from baseline in NSA-16 total score was –11.6 and –8.5 among the placebo group. Patients enrolled in Europe exhibited a significant improvement in NSA-16 total score at 26 weeks with pimavanserin vs. placebo.
Treatment-emergent adverse events occurred among 39.8% and 35.1% of patients in the pimavanserin and placebo groups, respectively, with headache and somnolence as the most common.
“I’m delighted with the latest results of the ADVANCE study because they strongly suggest that pimavanserin, when dosed at 34 mg, has significant efficacy on negative symptoms,” Nasrallah told Healio Psychiatry. “Although the results need to be confirmed with an additional pivotal study, these data are a very encouraging signal, leading me to believe that we’ll see more positive results in future clinical trials, which would enable Acadia Pharmaceuticals to submit those results to the FDA for approval in this use. Pimavanserin for the treatment of negative symptoms would truly be a major breakthrough, if approved.”