Long-acting risperidone injection combined with standard care appears to significantly delay time to initial relapse in patients with frequently relapsing bipolar disorder, according to a presentation at the fourteenth Biennial Winter Workshop on Schizophrenia and Bipolar Disorders.

The one-year, phase III trial is the first placebo-controlled study to explore use of a long-acting injection medication in maintenance treatment of frequently relapsing bipolar disorder, which is defined as four or more manic or depressive episodes in the previous year that require a doctor's care. This severe form of bipolar disorder may affect 20 percent of the 27 million people worldwide with bipolar disorder.

A total of 139 patients were randomized to 25-50mg long-acting risperidone intramuscular injection or placebo injections adjunctive to standard treatment. Patients receiving test medication plus standard treatment were eligible to enter the double blind phase of the trial if they met predefined criteria for being stable the last four weeks of the 16-week open-label stabilization phase.

The study compared the time to next mood episode, also known as a relapse, in patients receiving the test medication plus standard treatment versus patients receiving placebo plus standard treatment. For most patients, standard treatment consisted of mood stabilizers, antidepressants, anxiolytics or combinations.

Among patients randomized to test medication, 67 percent received a 25 mg dose, 29 percent received a 37.5 mg dose and 4 percent received a 50 mg dose, all administered once every two weeks.

The primary efficacy endpoint in the double-blind phase of the trial was the time from randomization to relapse, where relapse was defined as the first occurrence of a mood episode as determined by an independent Relapse Monitoring Board.

There was a significant difference in time to relapse, with a more than two-fold higher risk of relapse in the placebo group (47.8 percent) than the risperidone group (22.2 percent). In addition, scores on the Clinical Global Impression-Bipolar-Severity (CGI-BP-S) scale for overall bipolar disorder and the Clinical Global Impression-Bipolar-Change (CGI-BP-C) scale worsened significantly in the placebo group compared with the risperidone group.

Treatment-emergent adverse effects occurred more frequently in the group that received placebo and standard treatment (76.1 percent) than the group that received risperidone and standard treatment (70.8 percent), as did serious adverse effects (placebo, 19.4 percent; risperidone 13.9 percent). The most common adverse effects (greater than 5 percent) in the double-blind phase were tremor (risperidone, 23.6 percent; placebo, 16.4 percent), insomnia (risperidone, 19.4percent; placebo, 23.9percent), muscle rigidity (risperidone, 11.1 percent; placebo, 6 percent); weight gain (risperidone, 6.9 percent; placebo, 1.5 percent) and hypokinesia (risperidone, 6.9 percent; placebo, 0 percent). A total of 5 patients discontinued due to adverse events in the double-blind phase (3 in the risperidone group and 2 in the placebo group).

The time to relapse was significantly longer in patients receiving the test medication compared with placebo, and the relative risk of relapse was 2.4 times higher with placebo. The relapse rates were 47.8 percent with placebo and 22.2 percent with long-acting risperidone.

"Patients with frequently relapsing bipolar disorder require more healthcare interventions than patients with fewer episodes, and there is a huge unmet need for new treatments," said Dr. Joseph Calabrese, Co-Director of the Bipolar Disorders Research Center, University Hospitals Case Medical Center, Case Western Reserve University. Dr. Calabrese is a consultant to the study sponsors, Ortho-McNeil Janssen Scientific Affairs, L.L.C. "Risperidone long-acting injection is administered once every two weeks by a healthcare professional and avoids the need for patients to remember to take daily antipsychotic medications."