Atypical antipsychotic tolerability and switching strategies in bipolar disorder

Importance to the field: Atypical antipsychotics have unequivocally advanced the pharmacotherapy of bipolar disorders. These broad-spectrum treatments offer efficacy against core symptoms of acute mania, mixed state, depressed and maintenance phases of the disorder. Atypical antipsychotics are not, however, a panacea and are associated with several problematic tolerability and safety concerns. For example, emerging evidence militates against the original notion that atypical agents are without risk for extrapyramidal side effects and possibly tardive dyskinesia when compared to their therapeutic predecessors, the conventional antipsychotics. Although classified together, atypical antipsychotics are heterogeneous in their tolerability and safety profile, an issue relevant to individualizing treatment selection and switching antipsychotics for optimal clinical management. Areas covered in this review: This article reviews relevant adverse events attributable to the use of atypical antipsychotics and strategies for switching these agents, with particular attention to the bipolar disorder population. What the reader will gain: The reader will gain both a perspective of treatment-emergent adverse events associated with atypical agents in the treatment of bipolar disorder and a precise analysis of common adverse events that frequently lead to treatment discontinuation and/or switching to a separate agent. Take home message: Atypical antipsychotics provide for a different array of treatment-emergent adverse events than conventional agents. The therapeutic index of treatment is a ratio of the relative benefit divided by the probability of harm (i.e., side effects). Taken together, the atypical antipsychotics offer an improved therapeutic index when compared to conventional agents in bipolar disorder. Nevertheless, atypicals fall short of the ideal, necessitating frequent discontinuation and switching.