Antipsychotic polypharmacy in schizophrenia: ‘Secret sauce or wild abandon?’

The treatment of schizophrenia has paradoxically become increasingly complex with the greater availability and choice among antipsychotic medications. At the same time, there is still substantial unmet need, as confirmed by recent large pragmatic trials in schizophrenia, which provides the therapeutic context for antipsychotic polypharmacy. For patients and clinicians, then, the question of "why and when do I combine medications? is now very challenging. All available evidence suggests that antipsychotic polypharmacy is common in clinical practice. Additionally, it is a topic of enduring interest among clinicians who are always eager to understand the information contributing to key therapeutic strategies. This chapter will provide a current appraisal of the extant evidence-base that informs the daily decision making process that is the clinician's dilemma: how should I use antipsychotic polypharmacy to its best advantage in my practice? The chapter will also critically evaluate the extent to which polypharmacy truly impacts tolerability considerations in treating schizophrenia