AMSTERDAM – Patients with schizophrenia given the investigational drug cariprazine showed statistical improvements in negative symptoms such as apathy and withdrawal, compared with those given risperidone, results from a phase III clinical trial have shown. The data were presented at the annual congress of the European College of Neuropsychopharmacology.
Both drugs are antipsychotics, but risperidone is a dopaminergic antagonist, and cariprazine is a D2 and D3 receptor partial agonist, tending toward the D3 receptor. Currently, no drugs are on the market with a specific indication for treating the negative symptoms of schizophrenia, although several second-generation antipsychotics reduce negative symptoms as well as positive and general symptoms of schizophrenia. Several pharmacotherapies are available to treat the positive symptoms of the illness.
In this multicenter, international, double-blind study, 230 adults with schizophrenia were randomly assigned to receive cariprazine and 231 were assigned risperidone for 26 weeks, reported Dr. György Németh, one of the study’s lead authors and chief medical officer of the study’s sponsor, Gedeon Richter.
People included in the study had been stable for at least 6 months prior to screening, and for a subsequent 4 weeks prior to randomization. Those with a score of at least 24 or greater on the Negative Factor Scale of the Positive and Negative Syndrome Scale (PANSS-NFS) and a score of at least 4 on two of the three core negative symptoms, along with positive factor scores on the PANSS of at least 19 or more were considered for inclusion in the study. At baseline, both groups had similar PANSS scores: Negative factor scores in the study drug arm were 27.7 and 27.5 in controls. Positive factor scores were also similar: 8.8 in the study arm and 8.6 in controls.
Study participants also were measured at baseline on the Personal and Social Performance Scale. Scores were 48.8 in the study drug arm and 48.1 in the risperidone arm.
After a 2-week period of cross-titration and washout of previous medications, patients were treated with the target dose of 4.5 mg daily of their assigned drug for 24 weeks.
In the 77.4% of enrollees in both cohorts who completed the trial, those treated with cariprazine had the most improvement in both negative symptoms and personal and social performance, compared with the control group. At 26 weeks, the overall change from baseline in the study group for negative factor symptoms was –2.39, compared with –0.53 in controls (95% confidence interval; P = .002). Personal and social performance scores changed at 26 weeks from baseline by 2.71 in the study group and 6.56 in controls (95% CI; P less than .001).
Discontinuation rates were low, and the most common side effects were insomnia and headache (about 10% for each), mostly in the risperidone arm.
Dr. David Pickar, who was not involved in the study, said in an interview that when treating patients with schizophrenia “improvement in negative symptoms occurs a fair amount with improvements in positive symptoms. The problem is the persistence of negative symptoms,” said Dr. Pickar of the department of psychiatry at Johns Hopkins University, Baltimore, and former branch chief of intramural experimental therapeutics at the National Institute of Mental Health.
This trial was sponsored by Gedeon Richter.
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