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.

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.^2–4 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.