1. In this randomized controlled trial, patients with Major depressive disorder with psychotic features who were stable on olanzapine and sertraline showed higher relapse upon discontinuation of olanzapine than those who remained on both drugs over 36 weeks.
2. Patients who remained on both drugs had more weight gain but no significant differences in metabolic markers.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Major depressive disorder with psychotic features (MDD-p) is a debilitating form of depression typified by delusions and/or hallucinations that are generally treated with combination antidepressant and antipsychotic therapy. However, once a patient is stable, it is unclear if remaining on the antipsychotic is necessary to prevent relapse. In this randomized controlled trial, patients with MDD-p who were stable on olanzapine and sertraline showed higher relapse upon discontinuation of olanzapine than those who remained on both drugs over 36 weeks. While remaining on olanzapine increased the risk of weight gain, changes in other metabolic markers including LDL, HDL, and HbA1c were unaltered. Rates of parkinsonism but not akathisia were also higher in the continuation group.
The difference in relapse rates between groups was high and suggests a clear benefit of remaining on dual therapy even when stabilized. However, the risks of weight gain and extrapyramidal symptoms are important trade-offs that should be discussed with patients, and longer durations on olanzapine may eventually lead to metabolic marker abnormalities not captured by this relatively short study period. In addition, future studies determining an optimal window for withdrawal of antipsychotics and optimal tapering protocols would enhance these results.
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