Psychopharmacology of the negative symptoms: current status and prospects for progress

The past decade has witnessed a resurgence of interest in the development of novel pharmacological agents to treat the negative symptoms of schizophrenia. This review provides an overview of pharmacological approaches that have been evaluated as potential treatments and describes the emergence of several promising new approaches. First, we briefly describe recent methodological developments, including consensus-based clinical trial guidelines for patient selection criteria, symptom assessment, and trial duration. Next, we overview mono- and adjunctive-therapies that have been evaluated, including first- and second-generation antipsychotics, antidepressants, psychostimulants, molecules targeting cholinergic and glutamatergic systems, and hormones. We highlight the most promising pharmacological agents on the horizon, including glycine transporter-1 inhibitors, α7-nicotinic receptor positive allosteric modulators, and oxytocin, as well as non-pharmacological electromagnetic stimulation approaches. Further investigations, using optimal clinical trial design, hold considerable promise for discovering effective treatments for these functionally disabling symptoms in the near future.