Cariprazine Joins Growing Group of Approved Antipsychotics

Last month, the Food and Drug Administration approved Vraylar (cariprazine, a dopamine D2, D3 receptor partial agonist) for the acute treatment of manic or mixed episodes in bipolar I disorder as well as for the treatment of schizophrenia in adults.

The FDA go-ahead signals the end of a more than two-year effort to get the medication approved by the agency and comes at a time when the field of antipsychotics has seen significant change.

In fact, much has changed in just the past few months for oral antipsychotics; back in April, the popular drug Abilify (aripiprazole) went generic, while in July another new dopamine receptor partial agonist Rexulti (brexpiprazole) got FDA approval.

Long-acting injectable antipsychotics, which need to be administered only every few weeks and have the potential of reducing the risk of nonadherence and patient relapse, have also attracted attention in recent months. Several articles have been published recently—such as a JAMA Psychiatrystudy comparing oral versus long-acting risperidone in schizophrenia—that suggest long-acting injectable antipsychotics may offer advantages over some oral medications.

University of Maryland

However, there will always be a place for daily medication, noted William Carpenter, M.D., a professor of psychiatry and pharmacology at the University of Maryland School of Medicine. He believes cariprazine can carve out a solid niche in schizophrenia therapy.

“There are a couple of findings related to this drug’s effects that were interesting,” Carpenter told Psychiatric News. “One, cariprazine is also approved to treat mania in bipolar patients, and mania is not infrequently a symptom of schizophrenia. Other drugs may also help with mania, but cariprazine does have the clinical evidence to suggest using this drug when schizophrenia presents with mania.

“The other symptom is depression, which is quite common among schizophrenia patients, particularly early in the course of the disease,” he continued. “While it’s not been approved yet, there is evidence that cariprazine has an effect on mood in both major depression and bipolar depression, so that might increase the likelihood cariprazine will be prescribed for schizophrenia patients with depression.”

During the buildup to cariprazine’s approval, one aspect of the drug that received the most attention was its ability to improve the negative symptoms of schizophrenia as well as the positive ones (Psychiatric News, August 20). However, in the end the data were not strong enough to officially sanction this indication.

“For this drug, the negative improvements were noticeable, but the research could not definitely prove that the negative-symptom changes were not secondary to the positive outcomes,” Carpenter said.

As an example, he cited social withdrawal, a common occurrence in schizophrenia. In part, the withdrawal may be due to an underlying lack of motivation (considered a negative symptom of schizophrenia), but it can also be influenced by the patient’s suspicion and paranoia. If a patient’s social levels improve when taking an antipsychotic, these improvements may be solely due to a decrease in psychosis.

“The FDA was sharp on this,” Carpenter continued. “If you want a drug to have a negative-symptom indication, you need to show improvements in the absence of alternative explanations.”

Validation of the negative-symptom effects may still occur though, Carpenter noted. In a recent study testing cariprazine in a rat model of anhedonia, the drug showed greater potency at improving motivation than did aripiprazole. Animal findings do not always translate to humans, but at the moment there is at least a biologically plausible hypothesis that cariprazine may have true negative symptom effects. ■