Background: The suggestion that the neurohormone oxytocin may have clinical application in the treatment of schizophrenia was first published in 1972. Since then, a considerable body of research on a variety of fronts – including several recent double-blind treatment trials – has buttressed these early reports, providing support for the assertion that the oxytocin system is a promising and novel therapeutic target for this devastating malady. Herein, we review the diverse, convergent lines of evidence supporting the therapeutic potential of oxytocin in psychotic illness.

Methods: We performed a systematic review of preclinical and clinical literature pertaining to oxytocin's role in schizophrenia.

Results: Multiple lines of evidence converge to support the antipsychotic potential of oxytocin. These include several animal models of schizophrenia, pharmacological studies examining the impact of antipsychotics on the oxytocin system, human trials in patients examining the aspects of the oxytocin system and several double-blind, placebo-controlled clinical treatment trials.

Conclusions: There exists considerable, convergent evidence that oxytocin has potential as a novel antipsychotic with a unique mechanism of action. Auspiciously, based on the few chronic trials to date, its safety profile and tolerability appear very good. That said, several critical clinical questions await investigation before widespread use is clinically warranted.