Olanzapine discontinuation leads to higher relapse in depression with psychosis

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.

Click to read the study in JAMA

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In-Depth [randomized controlled trial]: The Study of the Pharmacotherapy of Psychotic Depression-II (STOP-PD-II) recruited 126 adult patients with MDD-p who were stable for 8 weeks on dual sertraline (150-200 mg) and olanzapine (15-20mg) therapy to be randomized to discontinue or continue olanzapine for 36 weeks over 4 medical centers. Included patients had a MDD-p diagnosis and a Hamilton Depression Rating Scale score of >21 and a score of >2 on the Schedule for Affective Disorders and Schizophrenia as well as >1 score on the Delusion Assessment Scale. Excluded patients had another psychotic disorder, bipolar disorder, or intellectual disability, body-dysmorphic or obsessive compulsive disorders, dementia, significant substance abuse, neurologic disease affecting motor ability, type 1 diabetes, unstable physical illness. To be included, patients must have been at least in near remission for 12 weeks plus an 8 week stabilization period. The risk of relapse was higher with discontinuation of olanzapine (Hazard Ratio 0.25; CI95 0.13 to 0.48), representing a number needed to treat of 2.8 and was significant when controlling for age, remission versus near remission, and study site. Continuation of olanzapine was associated with significant daily rate of increased weight gain (0.13 lb; CI95 0.11 to 0.15), waist circumference (0.009 inches; CI95 0.004 to 0.014), and total cholesterol (0.29mg/dL; CI95 0.13 to 0.45) but not LDL (0.04mg/dL; CI95 −0.01 to 0.10), HDL (−0.01mg/dL; CI95 −0.03 to 0.01), triglycerides (−0.153mg/dL; CL95 −0.306 to 0.004), glucose (−0.02mg/dL;CI95 −0.12 to 0.08), or HbA1c levels (−0.0002mg/dL; CI95 −0.0021 to 0.0016). Rates of parkinsonism scores on the Simpson-Angus Scale were higher with continuation (p = 0.009) but not rates of akathisia (4.7% vs 4.8%).

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