Objectives: To compare the 12-month clinical outcome of patients attending a depot clinic who were changed to oral atypical antipsychotic medication, with those who remained on depot preparations. Method: A systematic review of the case records of all patients aged between 18 and 65 attending the depot clinic at Fremantle Hospital, Western Australia. Results: The records of 72 patients were identified (mean age 43.3 years; duration of illness 8.5 years; 37% female); 71% had schizophrenia. Twenty-five patients were successfully switched to an oral atypical antipsychotic (34%), 34 controls remained on a depot (47%), five were managed on a combination of a depot and an atypical, and eight returned to depot medication after a trial of an oral atypical. At 12 month follow-up, patients on oral atypicals showed significant improvement on the CGI (z=-2.57, p=0.01), less akathisia (z=-2.12, p=0.03), and reduced use of antiparkinsonian medication (z=-1.97, p=0.04); these changes were not mirrored in the controls. On multivariate analysis, being on an atypical agent was an independent predictor of improved outcome as measured by the CGI scale (t=-2.1, p=0.04), but also weight gain (t=-2.9, p=0.006). Conclusions: This retrospective survey reveals that a proportion of patients on depot antipsychotic medication can successfully be changed to oral atypical agents, with enhanced clinical outcomes. Declaration of interest: This study was supported by an investigator-initiated grant to SK and DC from Janssen Cilag. DC has received honoraria, travel support, and other grant funding from both Janssen Cilag and Eli Lilly.