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Comparing Effectiveness of Psychotropic Medications

JAMA Psychiatry; ePub 2019 Feb 20; Stroup, et al

Recent findings suggest that in the treatment of schizophrenia, adjunctive antidepressants are associated with better outcomes compared with alternative psychotropic medication strategies. This comparative effectiveness study used US national Medicaid data from January 1, 2001, to December 31, 2010, to examine the outcomes of initiating treatment with an antidepressant, a benzodiazepine, a mood stabilizer, or another antipsychotic among adult outpatients (aged 18-64 years) diagnosed with schizophrenia who were stably treated with a single antipsychotic. Data analysis was performed from January 1, 2017, to June 30, 2018. Researchers found:

  • The study cohort included 81,921 adult outpatients diagnosed with schizophrenia (mean [SD] age, 40.7 [12.4] years; 37,515 women [45.8%]) who were stably treated with a single antipsychotic and then initiated use of an antidepressant (n=31,117), a benzodiazepine (n=11 941), a mood stabilizer (n=12,849), or another antipsychotic (n=26,014).
  • Compared with initiating use of another antipsychotic, initiating use of an antidepressant was associated with a lower risk of psychiatric hospitalization, whereas initiating use of a benzodiazepine was associated with a higher risk; the risk associated with initiating use of a mood stabilizer was not significantly different from initiating use of another antipsychotic.


Stroup TS, Gerhard T, Crystal S, et al. Comparative effectiveness of adjunctive psychotropic medications in patients with schizophrenia. [Published online ahead of print February 20, 2019]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2018.4489.


This study addresses the important clinical question of “What next?” when antipsychotic medication treatment fails to deliver adequate response. Strengths of the study include the large sample, rigorous methods to target individuals started on a new psychotropic, propensity weighting to help account for background characteristics, and the pragmatic outcomes. These findings underscore the potential benefit of antidepressant drugs in the therapeutic armamentarium for schizophrenia. New starts with benzodiazepines were associated with more risk, although it must be noted that the study methods did not provide information on why the new psychotropic was initiated. It is also interesting to note that more than half of eligible individuals in this large dataset were excluded from the main analysis because they were already taking multiple psychotropic medications. Comparative effectiveness studies can help inform future work, such as pragmatic randomized clinical trials, which might help better understand the relative risks vs benefits to changing medication treatment when individuals have sub-optimal response to a trial of antipsychotic medication.—Martha Sajatovic, MD, Professor of Psychiatry and of Neurology; Willard Brown Chair in Neurological Outcomes Research; Director, Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center; Case Western Reserve University School of Medicine.