Given the complex nature and frequent comorbidities of bipolar disorder (BD), polypharmacy is often used to achieve and maintain remission. In clinical practice, this is frequently the rule rather than the exception. Although research on BD uncommonly involves controlled clinical studies for combination therapies, clinicians nonetheless utilize polypharmacy as the best clinical treatment. A selective review of the literature for the best use of combination therapies, chiefly antipsychotics and mood stabilizers, has been carried out in order to offer rational indications.
Findings from studies on the concomitant use of antipsychotics and mood stabilizers have been reported for the different phases of mania: acute agitation, acute phase and remission phase. Guideline recommendations have also been reported.
Second generation antipsychotics (SGAs), particularly if available in intramuscular and oral formulations, give clinicians the possibility of continuity of pharmacotherapy, in terms of efficacy and tolerability. Association of MSs and SGAs in the treatment of mania increases efficacy compared with monotherapy in all the phases of the disorder. Accordingly, combination therapy should be the treatment of choice, particularly for severe manic and treatment-resistant episodes.
Several combinations of MSs with SGAs appear to be safe and effective, and provide good results as often reflected in published data. Polypharmacy, as well as polypsychotherapy, and complex combination therapy, may be the best means to balance the complexity and comorbidities of BD. However, clinical vigilance and safety monitoring are relevant aspects when polypharmacy is used.