Predictors of Treatment Discontinuation and Medication Nonadherence in Patients Recovering From a First Episode of Schizophrenia, Schizophreniform Disorder, or Schizoaffective Disorder: A Randomized, Double-Blind, Flexible-Dose, Multicenter Study

Objective: To evaluate predictors of treatment discontinuation against medical advice and poor medication adherence among first-episode patients treated with olanzapine, quetiapine, or risperidone.

Method: First-episode patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder (DSM-IV) were randomly assigned to olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) as part of a 52-week, randomized, double-blind, flexible-dose, multicenter study. Patients were enrolled from 2002 to 2004 at one of 26 sites in the United States and Canada. Survival analysis tested for predictors of treatment discontinuation against medical advice, while mixed models tested for predictors of poor medication adherence. Significant findings from the final models were replicated in sensitivity analyses.

Results: Of the 400 patients randomly assigned to treatment, 115 patients who discontinued treatment against medical advice and 119 study completers were compared in this analysis. Poor treatment response (p < .001) and low medication adherence (p = .02) were independent predictors of discontinuation against medical advice. Ongoing substance abuse, ongoing depression, and treatment response failure significantly predicted poor medication adherence (p < .01). Higher cognitive performance at baseline and ethnicity (black) were also associated with lower medication adherence (p < .05). An association between poor medication adherence and illness insight at study entry was found at trend level (p = .059).

Conclusion: This study highlights the importance of treatment response in predicting discontinuation against medical advice and poor adherence to medication in first-episode patients. These results also support interventions to improve adherence behavior, particularly by targeting substance use disorders and depressive symptoms.