: Both psychiatric polypharmacy and multimorbidity are common in depressed adults. We examine recent patterns of psychotropic polypharmacy with attention to concurrent multimorbidity in the treatment of depressive disorders in outpatient psychiatric care.

: Data from the 2006–2015 National Ambulatory Medical Care Survey offer nationally representative samples of office-based psychiatric care in adults with depressive disorders (ICD-9-CM codes 296.20–296.26, 296.30–296.36, 300.4, 311, and 301.10–301.13) (n = 6,685 unweighted). These data allowed estimation of the prevalence of polypharmacy (within-class, between-class, and both) involving four major psychotropic classes: antidepressants, antipsychotics, mood-stabilizers, and sedative-hypnotics. We further evaluated the proportion of within-class and between-class psychotropic prescription combinations that were potentially justifiable, taking FDA-approved indications and multimorbidity into consideration.

: Prescribing two or more psychotropic medications for depressed adults remained substantial and stable ranging from 59.0% in 2006–2007 to 58.0% in 2014–2015. The most common within-class polypharmacy types were: antidepressants (22.7%) and sedative-hypnotics (14.8%). The most common between-class polypharmacy types were: an antidepressant and a sedative-hypnotic (30.7%), an antidepressant and an antipsychotic (16.4%), and an antipsychotic and a sedative-hypnotic (9.0%). In visits in which between-class psychotropics were prescribed, 53.9% were potentially justified by FDA-approved augmentation and/or adjunctive treatment strategies or by psychiatric multimorbidities.

: Psychotropic polypharmacy affects more than half of depressed adults. Between-class polypharmacy is the most common pattern and in over 50% of instances may be justified by augmentation strategies or considerations of psychiatric multimorbidity. Future research is needed to address effectiveness, safety, and cost-effectiveness of polypharmaceutical care for depression, especially those occurring with psychiatric co-morbididities.