Focus on antipsychotic polypharmacy: evidence-based prescribing or prescribing-based evidence?

Clinicians treating patients with antipsychotic medications have long attempted to optimize outcomes in their patients by adapting evidence from clinical trials to clinical practice settings (Stahl, 1999a). However, there is little evidence to guide what to do when patients have poor responses. In such cases, many clinicians attempt innovative combinations of medicines. On the one hand, when such attempts are ahead of the evidence, such as combining agents with different mechanisms of action (e.g. mood stabilizers added to atypical antipsychotics), they can lead to hypothesisgenerating ideas that are confirmed with controlled trials (Casey et al., 2003). On the other hand, when such attempts are beyond the evidence, such as combining two fundamentally similar antipsychotics together, they can lack theoretical foundation, generate misleading information, set into motion irrational prescribing habits, and create more costs than benefits for patients (Stahl, 1999b,c, 2002a,b ; Stahl and Grady, In Press).