Results from a six-week study show patients with major depressive disorder treated with brexpiprazole had significantly reduced risk of akathisia and other side effects.
One of the potentially serious side effects of the drug aripiprazole (brand name: Abilify), which is approved to treat schizophrenia, bipolar disorder I, autism-related irritability, and as an adjunctive therapy to antidepressants for major depressive disorder, is akathisia, or a kind of restlessness.
At the 2014 annual meeting of the American Psychiatric Association in New York City, NY, on May 5, Otsuka Pharmaceutical Co. of Japan released promising results from a phase III trial of a second-generation version of aripiprazole, called brexpiprazole, which seems to reduce those adverse effects.
If approved by the US Food and Drug Administration, the new compound could extend the company’s franchise after aripiprazole loses patent protection, which is scheduled to occur in April 2015.
According to Michael Thase, MD, a professor of psychiatry at the University of Pennsylvania and the lead investigator on the trial, the 379 patients in the randomized, placebo-controlled trial of brexpiprazole, which ended in late 2012, exhibited “a two-thirds reduction in the chance of having restlessness.” By comparison, he said that one in three patients on aripiprazole experience restlessness. This can include symptoms such as an inability to sit still, fidgeting, pacing, constant movement of the feet, rocking, crossing and uncrossing the legs while sitting, and a general inner restlessness.
In order to continue on aripiprazole, such patients may need an antidote, such as a beta-blocker or a benzodiazepine.
The FDA lists restlessness as a common and serious side effect of aripiprazole, along with the more rare and more serious condition tardive dyskinesia, or uncontrollable movements of the face, tongue, or other parts of the body.
In the current study, brexpiprazole appeared to be as effective as aripiprazole as an add-on medication in treating major depressive disorder, as gauged by standard measures such as the MADRS, SDS, CGI, HAM-D, and HAM-A scores. For instance, Thase said, patients treated with brexpiprazole showed a 50% reduction in MADRS symptoms such as sadness and loss of interest, compared with a 20% reduction for patients who received placebo. And 14.4% of those treated with brexpiprazole (27 out of 187) achieved a full remission, he said. By contrast, just 16 of the 191 patients on placebo (8.4%) achieved that level of improvement.
Major depressive disorder was the only condition tested in the six-week trial, although Thase said brexpiprazole is currently in clinical trials for schizophrenia, and he would recommend testing for bipolar disorder as well. Preliminary results from the study were also presented at the European Congress of Psychiatry in January.
During his presentation, Thase did not discuss whether brexpiprazole also reduces any of the other common side effects associated with aripiprazole, including nausea, vomiting, constipation, headache, dizziness, anxiety, or insomnia, or some of the most serious potential adverse effects, such as elevated blood sugar, high fever, stiff muscles, confusion, sweating, or change in pulse or heart rate.
Like the original medication, brexpiprazole is a partial dopamine agonist. But Thase said the second-generation formulation works at a reduced level, which may explain the reduction in side effects.