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Associations Between Medication Class and Subsequent Augmentation of Depression Treatment in Privately Insured US Adults

Ameli, Omid MD, MPH*; Soria-Saucedo, Rene MD, MPH, PhD; Smith, Eric G. MD, PhD, MPH‡§; Cabral, Howard J. PhD, MPH; Soley-Bori, Marina MA*; Kazis, Lewis E. ScD†¶

Journal of Clinical Psychopharmacology: June 2017 - Volume 37 - Issue 3 - p 323–331
doi: 10.1097/JCP.0000000000000687
Original Contributions

Importance Treatment augmentation is an important clinical decision in the pharmacotherapy for depression, yet few studies have examined the rates of treatment augmentation by medication class.

Objective The aim of this study was to examine which initial pharmacotherapies for depression are more likely than others to result in subsequent treatment augmentation.

Methods This study is a retrospective cohort analysis of administrative data of 214,705 privately insured US adults between the age of 18 and 64 years who were diagnosed with a new episode of depression in 2009. Propensity score–adjusted logistic regression and Cox regression were used to model the effect of the class of initial monotherapy on treatment augmentation. Risk adjustors included depression severity, comorbidities, provider type, insurance, and demographic characteristics.

Exposure The class of initial monotherapy and the health care provider type were the main independent variables of interest.

Main Outcome The outcome was the augmentation of monotherapy.

Results Thirty-four percent of individuals received treatment augmentation. Compared with selective serotonin reuptake inhibitor monotherapy, second-generation antipsychotics as the initial treatment were associated with significant increase in the likelihood of augmentation compared with the other classes (hazards ratio, 2.59; 95% confidence interval [CI], 2.51–2.68). This result was corroborated after propensity score adjustment (odds ratio, 2.85; 95% CI, 2.70–3.00) when comparing second-generation antipsychotics to the other classes of pharmacotherapy. The other significant predictor of treatment augmentation was the provider type. Mental health specialists were 27% more likely to augment a treatment compared with generalists (hazards ratio, 1.27; 95% CI, 1.25–1.30).

Conclusions The type of initial antidepressant therapy is associated with the chances of treatment augmentation. Second-generation antipsychotics progressed to augmentation more rapidly than the other classes.

Supplemental digital content is available in the text.

From the *Boston University School of Public Health, and †Boston University School of Public Health, Health Law Policy and Management Department, Boston; ‡Center for Healthcare Organization and Implementation Research, Edith Nourse Rogers Memorial Veterans Hospital, Bedford; §Department of Psychiatry, University of Massachusetts Medical School, Worcester; ∥Department of Biostatistics, Boston University School of Public Health, and ¶Center for the Assessment of Pharmaceutical Practices, Boston University School of Public Health, Boston, MA.

Received May 11, 2016; accepted after revision December 31, 2016.

Reprints: Lewis E. Kazis, ScD, Center for the Assessment of Pharmaceutical Practices, Department of Health Policy and Management, Boston University School of Public Health, 715 Albany St (T3-W), Boston, MA 02118 (e-mail:

The Center for the Assessment of Pharmaceutical Practices, Department of Health Policy and Management, Boston University School of Public Health, provided support for the design and conduct of the study; collection, management, analysis, and interpretation of the data; and review of the manuscript.

A poster based on the findings of this study was presented at the 167th American Psychiatric Association Annual Meeting in New York on May 5, 2014.

Supplemental digital contents are available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (

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