Manic Episode During Treatment With Aripiprazole

To the Editor: Atypical antipsychotics are being increasingly used for the treatment of bipolar disorder. Olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole received Food and Drug Administration approval for the management of this disorder. We report a case of possible induction of mania with the use of aripiprazole.

The temporal relationship of the manic symptoms to the initiation of aripiprazole and their resolution with discontinuation of this medication supports the assumption that the manic episode was induced by aripiprazole. Seven out of the eight criteria proposed by Aubry et al. for a switch into mania secondary to atypical antipsychotics were met, suggesting that aripiprazole was the proximate cause of this patient’s manic symptoms (2) .

Several possible mechanisms have been proposed for the induction of mania by atypical antipsychotics, including a high ratio of 5-HT ₂ /D ₂ receptor occupancy with risperidone and olanzapine, and monoamine reuptake inhibition antidepressant-like effect of ziprasidone (3) . Aripiprazole is a partial agonist at 5-HT _1A and partial antagonist at 5-HT _2A receptors (4) . It is a partial agonist at dopaminergic receptors with high affinity for D ₂ and D ₃ receptors and moderate affinity for D ₄ receptors (4) . Combined effect of antagonistic activity at 5-HT _2A and partial agonistic activity at D ₂ receptors, along with agonistic activity at 5-HT _1A receptors, may cause frontal dopamine release contributing to manic symptoms. In addition, the prolonged use of fluphenazine could have resulted in a functional hypodopaminergic state and upregulation of the postsynaptic D ₂ receptors, of which stimulation by aripiprazole could result in exacerbation of the manic symptoms.

Although this case report adds to the literature on atypical results of atypical antipsychotics, caution needs to be used while interpreting the results, since aripiprazole is approved for the treatment of acute mania. Possible differences in response to aripiprazole in patients with bipolar affective disorder versus those with schizoaffective disorder need to be investigated. Furthermore, a drug screen was not performed to assure the patient’s denial of substance abuse.