Better pharmacotherapy for schizophrenia: what does the future hold?

Despite the expansion of available antipsychotic drugs over the past 50 years, functional outcomes for individuals with schizophrenia have not markedly improved. These agents are efficacious for psychosis but do not adequately address other core domains of schizophrenia psychopathology, namely negative symptoms and cognitive impairment, which have a greater impact on functional outcomes, including vocational or academic performance and interpersonal relationships. In addition, treatment-refractory psychosis still precludes functional improvement in many patients. Schizophrenia is a clinical syndrome consisting of these domains, which likely have some disparities in their respective pathophysiologies. This suggests that drug development should look to other molecular targets besides the D2 receptor, which characterizes the mechanism of available medications for schizophrenia. In this report, we review novel pharmacologic approaches that aim to specifically address each individual domain of schizophrenia. The goal of this future pharmacotherapy strategy is to advance outcomes beyond psychosis remission and toward functional recovery.