Objective: Numerous case reports (53 between 1994 and 2003) caused concern with manic/hypomanic symptoms induced by atypical antipsychotic (AA) drugs. Its clinical relevance and causal link with AA antidepressant properties are largely unknown.
Method: We reviewed newly reported cases and clinical studies of AA-induced mania/hypomania between 2004 and 2010 in order to assess its prevalence and relation with mood disorders. Published studies were found through systematic database search (PubMed, Scirus, EMBASE, Cochrane Library, Science Direct).
Results: Our search disclosed 28 new cases of AA-induced manic or hypomanic symptoms, following treatment with olanzapine (seven cases), quetiapine (five cases), ziprasidone (five cases), aripiprazole (four cases), amisulpride (two cases), zotepine (two cases), perospirone (two cases) and paliperidone (one case). Twenty-four patients suffered from schizophrenia; only four had schizoaffective disorder. Only one of the five cases of mania/hypomania with ziprasidone was a patient with mood disorder. Four well-designed clinical trials in bipolar depression included AA-induced mania/hypomania as a secondary outcome (three with quetiapine and one with olanzapine) and showed non-superiority relative to placebo.
Conclusions: Thus, well-designed clinical trials suggest that AA-induced mania/hypomania is a marginal phenomenon. Moreover, in most of the 28 new reported cases, AAs do not seem to induce mania/hypomania via their antidepressant properties.