Treatment Outcomes of Depression: The Pharmacogenomic... : Journal of Clinical Psychopharmacology (original) (raw)

Original Contributions

The Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study

Mrazek, David A. MD, FRC Psych*; Biernacka, Joanna M. PhD*†; McAlpine, Donald E. MD*; Benitez, Joachim MD‡; Karpyak, Victor M. MD, PhD*; Williams, Mark D. MD*; Hall-Flavin, Daniel K. MD*; Netzel, Pamela J. MD*; Passov, Victoria MD§; Rohland, Barbara M. MD*; Shinozaki, Gen MD∥; Hoberg, Astrid A. RN, CNS*; Snyder, Karen A. BS*; Drews, Maureen S. BS¶; Skime, Michelle K. BA*; Sagen, Jessica A. BA*; Schaid, Daniel J. PhD†; Weinshilboum, Richard MD#; Katzelnick, David J. MD*

From the Departments of *Psychiatry and Psychology, and †Health Sciences Research, Mayo Clinic, Rochester, MN; ‡Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York Presbyterian—Allen Hospital, New York, NY; §US Department of Defense, Department of Behavioral Health, Heidelberg, Germany; ∥Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine University of Iowa Hospitals and Clinics, Iowa, IA; and Departments of ¶Information Technology, and #Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN.

Received April 11, 2013; accepted after revision October 7, 2013.

Reprints: David J. Katzelnick, MD, Baldwin Bldg 6A, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (e-mail: [email protected]).

This research was supported, in part, by National Institute of Health grants RO1 GM28157, U19 GM61388 (The Pharmacogenomics Research Network), U01 HG005137, R01 CA138461, as well as by a PhRMA Foundation Center of Excellence in Clinical Pharmacology award. This publication was supported by NIH/NCRR/NCATS CTSA grant number UL1 RR024150.

Clinical trials registry: clinicaltrials.gov, registration number NCT00613470

Supplemental digital content is 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 (www.psychopharmacology.com).

Abstract

Background

The effectiveness of selective serotonin reuptake inhibitors (SSRIs) in patients with major depressive disorder (MDD) is controversial.

Aims

The clinical outcomes of subjects with nonpsychotic MDD were reported and compared with the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study outcomes to provide guidance on the effectiveness of SSRIs.

Methods

Subjects were treated with citalopram/escitalopram for up to 8 weeks. Depression was measured using the Quick Inventory of Depressive Symptomatology—Clinician Rated (QIDS-C16) and the 17-item Hamilton Depression Rating Scale.

Results

The group of subjects with at least 1 follow-up visit had a remission (QIDS-C16 ≤ 5) rate of 45.8% as well as a response (50% reduction in QIDS-C16) rate of 64.8%, and 79.9% achieved an improvement of 5 points or higher in QIDS-C16 score. The Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study subjects were more likely to achieve a response than STAR*D study subjects. After adjustment for demographic factors, the response rates were not significantly different. When reporting the adverse effect burden, 60.5% of the subjects reported no impairment, 31.7% reported a minimal-to-mild impairment, and 7.8% reported a moderate-to-severe burden at the 4-week visit.

Conclusions

Patients contemplating initiating an SSRI to treat their MDD can anticipate a high probability of symptom improvement (79.9%) with a low probability that their symptoms will become worse. Patients with lower baseline severity have a higher probability of achieving remission. The Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study replicates many findings of the first phase of the STAR*D study after controlling for the differences between the studies.