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Adjunctive antidepressants tied to better outcomes in schizophrenia

Study findings indicated that adjunctive antidepressants were linked to a lower risk for psychiatric hospitalization and ED visits compared with alternative psychotropic medication strategies in patients with schizophrenia already taking an antipsychotic.

“The effectiveness of combinations of antipsychotic medications remains unclear; reviews of this treatment strategy agree on the need for further investigation,” T. Scott Stroup, MD, MPH, from the department of psychiatry, Columbia University Irving Medical Center and New York State Psychiatric Institute, and colleagues wrote in JAMA Psychiatry.

Researchers evaluated 10 years of data from 44 state Medicaid programs to compare the effectiveness of initiating different classes of psychotropic medications (ie, antidepressants, benzodiazepines, mood stabilizers) with starting a new antipsychotic in a large cohort of adult outpatients with schizophrenia stably treated with an antipsychotic.

The investigators examined psychiatric hospitalization, ED visits for a mental disorder and all-cause mortality on an intention-to-treat basis during the first year after initiation of one of the study medications.

The cohort included 81,921 outpatients with schizophrenia receiving stable treatment with a single antipsychotic and who then started taking an antidepressant (n = 31,117), a benzodiazepine (n = 11,941), a mood stabilizer (n = 12,849) or another antipsychotic (n = 26,014).

Analysis revealed that compared with starting another antipsychotic, initiating use of an

antidepressant was linked to a lower risk for psychiatric hospitalization (HR = 0.84; 95% CI, 0.8-0.88). However, adjunctive benzodiazepine use was tied to a higher risk for hospitalization (HR = 1.08; 95% CI, 1.02-1.15) and the risk tied to initiation use of a mood stabilizer was not significantly different from initiation of another antipsychotic (HR = 0.98; 95% CI, 0.94-1.03).

Stroup and colleagues also observed similar associations with psychiatric ED visits for patients with schizophrenia initiating use of:

• an antidepressant (HR = 0.92; 95% CI, 0.88-0.96);
• a benzodiazepine (HR = 1.12; 95% CI, 1.07-1.19); and
• a mood stabilizer (HR = 0.99; 95% CI, 0.94-1.04).

In addition, patients who began taking mood stabilizers were more likely to be at increased risk for mortality (HR = 1.31; 95% CI, 1.04-1.66), according to the results.

“The increasing evidence base that supports adjunctive antidepressant treatment in schizophrenia suggests the need for increased clinical interest in this treatment strategy,” the researchers concluded. “Applied broadly, improved pharmacologic treatment of schizophrenia and consequent reduced need for hospitalization and ED visits associated with more antidepressant and less benzodiazepine use would represent a significant benefit for individuals and for public health.”

Though promising, these results should be confirmed in future randomized, controlled trials (RCTs), Donald C. Goff, MD, from the Nathan Kline Institute for Psychiatric Research, New York University School of Medicine, cautioned in a related editorial.

“Beyond the well-established benefits of clozapine, prescribers seeking to improve outcomes in patients with schizophrenia have limited evidence from high-quality RCTs to guide add-on strategies,” he wrote. “If clinicians and patients choose to implement add-on treatments after weighing results from both observational studies and RCTs, the limitations of the evidence should be acknowledged, and outcomes should be carefully monitored.” – by Savannah Demko

Disclosures: Stroup reports being an investigator in a clinical trial sponsored by Auspex Pharmaceuticals and participating in a presentation supported by Intra-Cellular Therapies Inc. Please see the study for all other authors’ relevant financial disclosures. Goff reports grants from Avanir Pharmaceuticals.