Serum Prolactin Levels Among Outpatients With Major Depressive Disorder During the Acute Phase of Treatment With Fluoxetine 

George I. Papakostas, M.D.; Karen K. Miller, M.D.; Timothy Petersen, Ph.D.; Katherine G. Sklarsky, B.A.; Sarah E. Hilliker, B.A.; Anne Klibanski, M.D.; and Maurizio Fava, M.D.

Objective: To determine changes in serum prolactin levels in outpatients with DSM-IV-diagnosed major depressive disorder (MDD) following a 12-week open-label trial of fluoxetine.

Method: 87 outpatients enrolled in the trial had serum prolactin levels determined at baseline and during their final visit (week 12 or discontinuation visit). In addition, serum testosterone levels were measured in 44 of the 46 men during these 2 visits. Hyperprolactinemia was defined as a serum prolactin level greater than 16.5 ng/mL or 18.9 ng/mL for men and women, respectively. The study was conducted from September 1997 to March 2002.

Results: Of 80 patients with normal prolactin levels at baseline, 10 (12.5%) developed hyperprolactinemia following fluoxetine treatment. Specifically, 2 (4.5%) of 44 men and 8 (22.2%) of 36 women with normal prolactin levels at baseline developed hyperprolactinemia following treatment with fluoxetine (p = .0174 for between-gender difference). In addition, there was a significant increase in mean ± SD serum prolactin levels following treatment with fluoxetine in all patients with normal baseline prolactin levels (6.4 ± 3.4 to 10.0 ± 7.0 ng/mL, p = .002). There were no significant changes from baseline in testosterone levels in men following fluoxetine treatment (448.4 ± 139.6 to 439.5 ± 142.1 ng/dL, p > .05; normal above 245 ng/dL), while none of the 44 men developed low testosterone levels following fluoxetine treatment.

Conclusion: 4.5% of men and 22.2% of women with MDD developed new onset hyperprolactinemia following fluoxetine treatment.

(J Clin Psychiatry 2006;67:952-957)

Received July 26, 2005; accepted Nov. 30, 2005. From the Depression Clinical and Research Program, Department of Psychiatry (Drs. Papakostas, Petersen, and Fava and Mss. Sklarsky and Hilliker), and the Neuroendocrine Unit, Department of Medicine (Drs. Papakostas, Miller, and Klibanski), Massachusetts General Hospital, Harvard Medical School, Boston.

Supported by National Institute of Mental Health grants #K23 MH069629, 5R10-MH-56057-05, and M01-RR-01066, as well as the Depression Clinical and Research Program and Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston.

Dr. Papakostas has been a consultant to, has received honoraria from, and has served on the speakers or advisory boards of GlaxoSmithKline and Pfizer and has received grant/research support from GlaxoSmithKline and Bristol-Myers Squibb. Dr. Fava has received research support from Abbott Laboratories, Lichtwer Pharma GMbH, and Lorex; has received honoraria from Bayer AG, Compellis, Janssen, Knoll, Lundbeck, Dov, Biovail, BrainCells, Cypress, Fabre-Kramer, Grunenthal GMbH, MedAvante, Sepracor, and Somerset; and has received both research support and honoraria from Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest, GlaxoSmithKline, Johnson & Johnson, Novartis, Organon, Pharmavite, Pfizer, Roche, Sanofi-Synthelabo, Solvay, and Wyeth-Ayerst. Drs. Miller, Petersen, and Klibanski and Mss. Sklarsky and Hilliker report no other significant commercial relationships relevant to the study.

Corresponding author and reprints: George I. Papakostas, M.D., Massachusetts General Hospital, Department of Psychiatry, Depression Clinical and Research Program, 15 Parkman St., WACC 812, Boston, MA 02114 (e-mail: gpapakostas@partners.org).