15 Years of Clinical Experience With Bupropion HCl: From Bupropion to Bupropion SR to Bupropion 40

Maurizio Fava, M.D.; A. John Rush, M.D.; Michael E. Thase, M.D.; Anita Clayton, M.D.; Stephen M. Stahl, M.D., Ph.D.; James F. Pradko, M.Sc., M.D.; and J. Andrew Johnston, Pharm.D.

Background: Bupropion has been available in the United States since 1989. Initially a thrice-daily immediate-release formulation, a twice-daily sustained-release formulation followed in 1996, and, in August 2003, a once-daily extended-release formulation was introduced. On the 15th anniversary of its introduction, we undertook a review of the background/history, mechanism of action, formulations, and clinical profile of bupropion.

Data Sources: Major efficacy trials and other reports were obtained and reviewed from MEDLINE searches, review of abstracts from professional meetings, and the bupropion SR manufacturer's databases. Searches of English-language articles were conducted from June 2003 through August 2004. No time limit was specified in the searches, which were conducted using the search terms bupropion, bupropion SR, and bupropion 40 .

Data Synthesis: Bupropion inhibits the reuptake of norepinephrine and dopamine neurotransmission without any significant direct effects on serotonin neurotransmission. Bupropion is an effective antidepressant with efficacy comparable to selective serotonin reuptake inhibitors and other antidepressants. It is well tolerated in short- and longer-term treatment. Headache, dry mouth, nausea, insomnia, constipation, and dizziness are the most common adverse events. Seizure and allergic reactions are medically important adverse events associated with bupropion and are reported rarely. Among all the newer antidepressants in the United States, bupropion appears to have among the lowest incidence of sexual dysfunction, weight gain, and somnolence. Although not U.S. Food and Drug Administration approved for these indications, bupropion has also been used as an adjunctive treatment to reverse antidepressant-induced sexual dysfunction and to augment antidepressant efficacy in partial responders and nonresponders to other agents.

Conclusion: Bupropion has played and will continue to play an important role as a treatment for major depressive disorder in adults, as well as for other related disorders.

(Prim Care Companion J Clin Psychiatry 2005;7:106-113)

Received Nov. 15, 2004; accepted April 6, 2005. From the Department of Psychiatry, Harvard Medical School and Massachusetts General Hospital, Boston (Dr. Fava); the Department of Psychiatry, University of Texas, Southwestern Medical Center, Dallas (Dr. Rush); the Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pa. (Dr. Thase); the Department of Psychiatric Medicine, University of Virginia, Charlottesville (Dr. Clayton); the Neuroscience Education Institute, University of California, San Diego (Dr. Stahl); Bay Pointe Depression Clinic, New Baltimore, Mich. (Dr. Pradko); and Innovaa Research, Chapel Hill, N.C. (Dr. Johnston).

The authors acknowledge GlaxoSmithKline in providing support for the manuscript preparation of this article.

Financial disclosure appears at the end of the article.

Corresponding author and reprints: J. Andrew Johnston, Pharm.D., Innovaa Research, 1016 Bowden Road, Chapel Hill, NC 27516 (e-mail: aj@innovaaresearch.com).