Letters to the Editor

Off-Label Uses for Selective Serotonin Reuptake Inhibitors


Am Fam Physician. 2005 Jan 1;71(1):43-46.

to the editor: In the August 1, 2003, issue of American Family Physician, Stone and colleagues reported on off-label applications for selective serotonin reuptake inhibitors (SSRIs).1 Unfortunately, the article1 was somewhat misleading and incomplete. The U.S. Food and Drug Administration (FDA) has approved several SSRIs for the treatment of generalized anxiety disorder. The FDA also has approved venlafaxine (Effexor), which is an SSRI in low doses but a dual action SSRI/serotonergic noradrenergic reuptake inhibitor (SNRI) in high doses, for this use. In fact, all SSRIs are equally effective in the treatment of all anxiety disorders (including panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, and social anxiety), whether or not they have received specific approval from the FDA for this purpose.2 SSRIs also have been found useful in treating eating disorders (bulimia, binge eating)3 and menopausal hot flushes (natural or induced by antihormone cancer treatment); paroxetine (Paxil), which also inhibits norepinephrine at higher doses, and venlafaxine have been more effective than the “pure” SSRIs for treating hot flushes.4 In fact, dual action (SSRI/SNRI) agents (higher-dose Effexor and Paxil) and tricyclic antidepressants have been shown to be helpful for neuropathic pain,5 fibromyalgia, and migraine prophylaxis,5 where pure SSRIs have been relatively ineffective.


show all references

1. Stone KJ, Viera AJ, Parman CL. Off-label applications for SSRIs. Am Fam Physician. 2003;68:498–504....

2. Recommendations for the long-term treatment of anxiety disorders. CNS Spectr. 2003;8(suppl 1).

3. Yager J, ed. Treatment of bulimia nervosa and binge eating disorder [Monograph]. University of South Florida College of Medicine. 2003.

4. Schober CE, Ansani NT. Venlafaxine hydrochloride for the treatment of hot flashes. Ann Pharmacother. 2003;37:1703–7.

5. Stahl SM. Here today and not gone tomorrow: the curse of chronic pain and other central sensitization syndromes. J Clin Psychiatry. 2003;64:863–4.

in reply: In our article,1 we selected six conditions for which the off-label use of selective serotonin reuptake inhibitors (SSRIs) had the most evidence. We certainly acknowledge that SSRIs are used off-label for other conditions, but we had to consider the space constraints of the journal. We did not include hot flushes in our article,1 but we find SSRIs (including venlafaxine, which also inhibits norepinephrine) to be very useful in relieving menopausal or perimenopausal hot flushes in women who are not taking (or cannot take) estrogen therapy.24 There is no doubt that in addition to the conditions mentioned in our article and the conditions mentioned by Dr. Hoffman, SSRIs will prove to be useful in other conditions. Likewise, SSRIs will be tried for other conditions and fail to show any benefit over placebo. Evidence, of course, takes time to accumulate.

Other SSRIs have come on the market since the writing of our article. At that time, of those available, only paroxetine had the FDA approval for generalized anxiety disorder. In a revision of our article, we had included venlafaxine, but that information was subsequently edited out. We appreciate Dr. Hoffman taking the time to write and for highlighting this additional useful information about SSRIs and venlafaxine.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Navy medical department or the U.S. Navy at large.


show all references

1. Stone KJ, Viera AJ, Parman CL. Off-label applications for SSRIs. Am Fam Physician. 2003;68:498–504....

2. Stearns V, Beebe KL, Iyengar M, Dube E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA. 2003;289:2827–34.

3. Loprinzi CL, Sloan JA, Perez EA, Quella SK, Stella PJ, Mailliard JA, et al. Phase III evaluation of fluoxetine for treatment of hot flashes. J Clin Oncol. 2002;20:1578–83.

4. Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, LaVasseur BI, Barton DL, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet. 2000;356:20596363.

Send letters to afplet@aafp.org, or 11400 Tomahawk Creek Pkwy., Leawood, KS 66211-2680. Include your complete address, e-mail address, and telephone number. Letters should be fewer than 400 words and limited to six references, one table or figure, and three authors.

Letters submitted for publication in AFP must not be submitted to any other publication. Possible conflicts of interest must be disclosed at time of submission. Submission of a letter will be construed as granting the AAFP permission to publish the letter in any of its publications in any form. The editors may edit letters to meet style and space requirements.

This series is coordinated by Kenny Lin, MD, MPH, Associate Deputy Editor for AFP Online.



Copyright © 2005 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions


Jan 2022

Access the latest issue of American Family Physician

Read the Issue

Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article