It has been shown that new antipsychotics (NAP) olanzapine or aripiprazole in combination with valproic acid or lithium are safe and improving the efficacy of the treatment of manic episode, and the mood stabilizing therapy in bipolar disorder (BD). NAP have less potent antidopaminergic action, and lover risk of Neuroleptic Malignant Syndrome (NMS) than typical antipsychotics.

59 years old male, with recent history of cognitive impairment, and long history of BD treated with combination of valproic acid, lithium and olanzapine was admitted to the hospital with acute manic episode. Because of ineffectiveness of the recent treatment there was added aripiprazole (15 mg/d) followed by slow reduction of olanzapine. After following 3 weeks the clinical symptoms of lithium intoxication, and the raising blood level of lithium (1,47 mmol/l) were observed, although the oral dose of lithium was not changed. The symptoms of intoxication disappeared during 10 days after lithium discontinuation. However, after the next 8 days of the treatment with aripiprazole combined with valproic acid - the NMS symptoms rapidly emerged and were lasting for 12 days

We have found in the literature description of NMS in the patient on aripiprazole combined with lithium, and in the patient with mental retardation treated with aripiprazole added to olanzapine. Our presentation reveals increased risk of toxic interactions between lithium and the new antipsychotic Aripiprazole, as so the possible role of neurobiological deficits as risk factors of NMS.