(Mar. 21, 2017) More than half of schizophrenia patients experience "negative symptoms," such as social withdrawal and lack of motivation that significantly reduce quality and satisfaction with life. Yet, even as medications to manage "positive symptoms" like hallucinations proliferated over the last several decades, effective medications to treat negative symptoms have persistently proven elusive.
Into this context comes a new study of cariprazine, a partial dopamine agonist from a class of antipsychotic drugs that work to regulate dopamine activity in the neurological pathways implicated in both positive and negative symptoms.
Cariprazine vs Risperidone
György Németh and colleagues enrolled more than 461 adult patients and 460 controls from 66 treatment centers in 11 European countries to compare the effects on negative symptoms of cariprazine versus those of the atypical antipsychotic risperidone. The primary measure of outcomes was the Positive and Negative Syndrome Scale factor score for negative symptoms (PANSS-FSNS).
Each group completed 26 weeks of treatment. In both the cariprazine and risperidone groups, side effects associated with starting new medication (e.g., insomnia, headache, anxiety) were reported in just more than half the participants. One patient in the risperidone group died of an unrelated cause.
In what is reported to be the only randomized controlled trial (RCT) to test the effectiveness of one antipsychotic against another in reducing negative symptoms, the study found cariprazine to be significantly superior to risperidone. Mean PANSS negative syndrome scores declined at least 20% in the group on cariprazine.
Other Cariprazine Findings
Dopamine partial agonists such as cariprazine emerged as a new antipsychotic class in the early 2000s amid hope they would bring relief from negative symptoms. Since then, treatment trials of cariprazine have produced the following reports:
- Three RCTs found cariprazine significantly reduced hostility compared with placebo as measured by PANSS. The effect of the medication was greater with higher levels of hostility at the outset of treatment.
- A multinational double-blind RCT found cariprazine significantly reduced the time to relapse versus placebo. Relapse occurred in 24.8% of the patients receiving cariprazine and 47.5% of those treated with placebo. Relapse was defined as worsening of measurable symptoms scores, psychiatric hospitalization, aggressive or violent behavior or suicide risk.
- In validated schizophrenia animal models, cariprazine has been found to significantly improve cognitive deficits and social functioning, highlighting the potential long-term efficacy of cariprazine in the treatment of negative symptoms in schizophrenia patients.
Cariprazine became available in the United States in March 2016 under the trade name Vraylar.* The drug was approved in September 2015 by the US Food and Drug Administration for the treatment of schizophrenia and bipolar disorder in adults.
* The Treatment Advocacy Center does not accept funding from companies or entities involved in the sale, marketing or distribution of pharmaceutical products.
Doris A. Fuller
Chief of Research and Public Affairs
References:
- Németh, G., et al. (6 February 2017). Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomized, double-blind, controlled trial. The Lancet.
- Lieberman, J.A. (April 2014). Dopamine partial agonists: A new class of antipsychotic. CNS Drugs.
- Citrome, L. et al. (2016). The effect of cariprazine on hostility associated with schizophrenia: Post hoc analyses from 3 randomized controlled trials. Journal of Clinical Psychiatry.
- Durgam, S. et al. (October 2016). Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial. Schizophrenia Research.
- Neill, J. C. et al. (2015). Effects of cariprazine, a novel antipsychotic on cognitive deficit and negative symptoms in a rodent model of schizophrenia symptomatology. European Neuropsychopharmacology.
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