Bad Messages About Good Treatments: The Case of Sexual Side-Effects

There is a substantial body of evidence indicating that SSRIs, the most popular antidepressants, e.g., fluoxetine (Prozac), cause more sexual side effects than some other antidepressants, e.g., bupropion (Wellbutrin).


Richard J. Metzner, M.D.

Clinical Professor

Semel Institute for Neuroscience and Human Behavior at UCLA


The explanation is that serotonin's influences, which SSRIs increase, tend to inhibit sexual functioning, while those of dopamine and norepinephrine, which bupropion augments, do the opposite. Multiple studies have confirmed this difference, and many clinicians prescribe accordingly.

Has the US Food and Drug Administration given an official indication distinguishing antidepressants in this manner? No. Bupropion has only been approved by the FDA for treatment of depression, not for reducing sexual side-effects. There are practical reasons why valid uses of medications might remain "off-label." It costs substantial money and time for pharmaceutical companies to do all the studies required to be granted an official FDA indication, but it takes only one indication to deliver a drug to market. Cost-benefit analyses favor leaving lesser indications off-label and letting professionals treat them without FDA sanction.

Does this mean that doctors who prescribe off-label or teach others to do it are doing something wrong? Not necessarily. Doctors, whom the FDA does not regulate, can prescribe medications for any medically justified purpose they choose.  In psychiatry, 31% of medications are prescribed for off-label purposes. In the case of bupropion and sexual side effects, the off-label use is frequently in the interests of patients.

But here's where the law comes in. Although doctors can prescribe and teach off-label treatments,  pharmaceutical companies, which the FDA does regulate, can't pay them to do it, even when the off-label use is scientifically accepted. The promotion of products for off-label indications by pharmaceutical companies is a federal offense. Part of the government's three billion dollar settlement against GlaxoSmithKline involved criminal charges for paying doctors to publicize Wellbutrin's relative lack of sexual side-effects.

Why were these laws broken? Clearly pharmaceutical companies want to get the profits from off-label indications without having to prove them to the government. Doctors, in turn, may rationalize that telling their colleagues about those indications promotes better patient care and justifies whatever they are being paid to do it. 

The take home message is this: Crimes can be committed when those teaching about effective medications do so in ways that violate regulatory laws. Ethical professionals should continue teaching about valid off-label treatment methods, but only in legally appropriate educational settings with the scientific evidence clearly designated and financial conflicts of interest fully disclosed. That kind of teaching will be far less likely to cast good treatments in a bad light.




Copyright 2012, Scaled Psychiatric Systems, Inc. All rights reserved