Methylphenidate infusion in euthymic bipolars: effect of carbamazepine pretreatment

A number of studies have reported attenuation by lithium (Li) pretreatment of the activating and euphoriant effects of psychostimulants. In view of increasing interest in the therapeutic potential of carbamazepine (CBZ) in bipolar disorder, we examined the effect of CBZ pretreatment on methylphenidate-induced behavioral activation and euphoria. Seven euthymic bipolar subjects received 2 weeks of pretreatment with CBZ or placebo in a double-blind crossover design. After each pretreatment period, the subjects received methylphenidate, 30 mg i.v.; mood and behavior changes were monitored for a period of 5 hours after each infusion. Methylphenidate induced a striking psychostimulant effect that was not attenuated by CBZ pretreatment. Possible implications of this finding for the antimanic efficacy of CBZ and for mechanisms of action are discussed.