POLYPHARMACY IN BIPOLAR-I DISORDER

There are currently three mood stabilizers available for the maintenan ce treatment of patients with bipolar I disorder: lithium, valproate, and carbamazepine. Unfortunately, monotherapy with each of these conve ntional agents often fails. To improve outcome, clinicians utilize pol ypharmacy. Although the efficacy of this practice is largely unknown, because of the lack of controlled studies, data from the United States and Europe indicate polypharmacy is the rule rather than the exceptio n. The few controlled trials that have been conducted indicate that (1 ) the specific combination of lithium plus imipramine provides no adva ntage over lithium monotherapy (notwithstanding the inadequacy of lith ium monotherapy); (2) the specific combination of lithium and the depo t neuroleptic flupenthixol provides no advantage over lithium monother apy; and (3) the combination of lithium plus carbamazepine may be as e ffective as lithium plus haloperidol for acute and continuation treatm ent. Most of the literature on polypharmacy consists of case reports, retrospective chart reviews, and open-label prospective studies, and d escribes the use of numerous combinations of medications, including li thium plus valproate, lithium plus carbamazepine, and valproate plus c arbamazepine. Preliminary findings suggest these combinations may be e ffective, and that clozapine and high-dose levothyroxine may each be u seful as well when combined with other drugs. Further research is nece ssary to formally evaluate whether these drug combinations are more ef fective than monotherapy. Until such studies are completed, certain ge neral principles regarding side effects, pharmacodynamics, and pharmac okinetics should be kept in mind when prescribing two or more medicati ons concurrently.