Combining a mood stabilizer with a second-generation atypical antipsychotic is more effective than monotherapy for preventing relapses in bipolar disorder, a review in the Journal of Affective Disorders shows.
However, combined treatments carry a greater risk of adverse effects, including potentially lethal conditions, especially when they are used long-term. As a result, clinicians should be cautious about prescribing these combination regimens. Such regiments should be reserved for patients who do not achieve clinical stability with monotherapy and do not have significant medical comorbidities, said Dr. Massimiliano Buoli of the University of Milan and his associates.
The investigators reviewed the literature on combined mood stabilizer plus antipsychotic therapy for the maintenance treatment of bipolar disorder, focusing on 19 studies published between 1980 and 2013.
"With some exceptions," they found combination therapy more effective than monotherapy at preventing relapses. But the paucity of high-quality data means that "it is probably too early to have a definitive opinion about the best atypical antipsychotic to combine with mood stabilizers," the researchers wrote (J. Affect. Disord. 2014;152:12-18).
First-generation antipsychotics should not be used in this way, however, as they raise the risk of motor adverse effects excessively.
Among atypical antipsychotics, quetiapine has accumulated the most evidence regarding efficacy. Ziprasidone and long-acting risperidone also boast low rates of relapse, compared with other agents.
Case reports indicate that all combined therapies with the exception of ziprasidone raise the risk of potentially fatal adverse events, including encephalopathy, Stevens-Johnson syndrome, neutropenia, and neuroleptic malignant syndrome. Olanzapine, risperidone, and quetiapine are associated with a higher risk of weight gain, and aripiprazole and ziprasidone have been linked to a higher risk of extrapyramidal side effects.
Dr. Buoli reported that he is a consultant for Roche, and his associate Dr. A. Carlo Altamura reported ties to Roche, Merck, and other companies.