In the dozen years since it was first introduced, Prozac and its close chemical relatives, the selective serotonin reuptake inhibitors, or SSRIs (Paxil, Zoloft, Luvox and Celexa), have become the nation's most popular antidepressants. They do a great job of parting the black clouds of depression, and many people swear that SSRIs have improved their lives dramatically.
But in addition to typical antidepressant side effects -- nausea, nervousness, insomnia, diarrhea, dry mouth and tremor (hand shaking) -- the SSRIs have become notorious for causing sex problems: libido loss, weak orgasms, difficulty in reaching or inability to reach orgasm and, in men, erection impairment. Depending on the study, 50 to 80 percent of SSRI users report at least one sexual side effect. Many SSRI users insist they are willing to forgo sexual satisfaction to escape from the horrors of depression. But others are unhappy about SSRI-induced sex problems.
Unfortunately, few people know that another antidepressant, Wellbutrin (chemical name: bupropion), is as effective as the SSRIs -- but much less likely to cause sexual side effects. And most don't know that several studies have shown that Wellbutrin has sex-enhancing effects.
"I've never seen a study showing that any SSRI is significantly superior to Wellbutrin as a treatment for depression," says drug expert Joe Graedon, coauthor with his wife, Teresa, of the "People's Pharmacy" books, syndicated newspaper column and syndicated radio program. "And like the SSRIs', Wellbutrin's nonsexual side effects are pretty mild and often transient. But in terms of sexual side effects, we're talking night and day. The SSRIs send your sex life down the toilet, but sex problems with Wellbutrin are rare. It's more likely to improve your sex life than hurt it."
So why are so few people familiar with Wellbutrin? Why does it languish in the long shadow cast by the vastly more popular -- yet sex-killing -- SSRIs? The answer involves a strange, ill-starred combination of bad luck, bad press and drug industry prudery back in the days before Viagra proved that there was gold below the belt. Two recent studies may begin to turn things around (except for the fact that they have received no press coverage).
In the mid-1980s, when Burroughs-Wellcome (now GlaxoWellcome) in North Carolina was working its way through the tedious process of demonstrating that Wellbutrin was safe and effective enough to win Food and Drug Administration approval, the company contracted with several laboratories to study the drug's side effects. (Wellbutrin is not an SSRI and is chemically unrelated to every other antidepressant medication; researchers are still not sure how it works.)
One safety study raised a major red flag. At high doses, about twice the recommended maximum, the original formulation of Wellbutrin triggered seizures in 0.4 percent of those who took it -- four people per 1,000. That may not sound like much of a hazard, but it was two to four times the seizure risk of other antidepressants, and it doesn't take too many car wrecks caused by seizures behind the wheel to cause sweaty palms at the FDA.
The study results were reported in the medical trade press, and you could almost hear the prescription pads snapping shut from coast to coast.
Burroughs-Wellcome scrambled to save its multimillion-dollar investment in Wellbutrin, and came up with a new slow-release (SR) formulation, now the standard prescription. Wellbutrin-SR caused seizures in only 0.1 percent of users, comparable to the seizure risk of Prozac and Paxil, and lower than the risk associated with Zoloft (0.2 percent), Luvox (0.2 percent) and Celexa (0.3 percent), according to the 2000 edition of the standard drug reference "Drug Facts and Comparisons."
But the damage had been done. Wellbutrin was a seizure-tainted drug. Today, a dozen years after its release, with no evidence of unusually high seizure risk, "Drug Facts and Comparisons" still includes a warning about its seizure risk. But there is no such warning for Zoloft, Luvox and Celexa, all of which cause seizures at a higher rate.
"Wellbutrin is an excellent antidepressant that has no more seizure potential then other antidepressants," says Roberta May, director of the Office of Psychiatric Research and an assistant professor of psychiatry at the University of Alabama at Birmingham, "but doctors still think it's dangerous. The exact same drug is now prescribed to help people quit smoking, but GlaxoWellcome changed its name to Zyban to get out from under Wellbutrin's bad reputation."
At the same time Burroughs-Wellcome was hip-deep in damage control over the seizure report, the company also contracted with the Crenshaw Clinic in San Diego to study Wellbutrin's sexual side effects. The Crenshaw Clinic (now closed) was operated by Theresa Crenshaw, M.D. (now retired), one of the nation's most prominent sex and drug researchers and coauthor of the medical text "Sexual Pharmacology." Crenshaw and her colleagues gave 60 men and women suffering from low libido and difficulty with orgasm either a placebo or Wellbutrin. Crenshaw knew that the SSRIs and most other antidepressants cause sex problems. She expected the placebo group's sex problems to improve a little, and the Wellbutrin group's to get worse. But a strange thing happened: In the placebo group, 3 percent reported improved sexual functioning, but in the Wellbutrin group, the figure was an astonishing 63 percent. "To our knowledge," Crenshaw concluded in the Journal of Sex and Marital Therapy (1987), "these results represent the first demonstration in a well-controlled clinical trial of an improvement in sexual dysfunction due to drug treatment."
An astonished Crenshaw rushed to tell Burroughs-Wellcome that Wellbutrin was more than just another antidepressant. It looked promising as the first effective drug treatment for sex problems. But oddly, Burroughs-Wellcome showed no interest in what Crenshaw considered a potential medical breakthrough, not to mention a commercial bonanza. "I knew they were preoccupied with the seizure business," she said, "but still, you'd think they would want to pursue my findings. They didn't. I got the feeling that they'd rather not know if their drug was a sex stimulant. I got the feeling they were prudes."
"The drug companies have had a historical anti-sexual bias," says Eli Coleman, professor and director of the Human Sexuality Program at the University of Minnesota in Minneapolis. "Of course, Viagra has changed that," but Crenshaw's study took place a decade before the erection pill was approved.
"Burroughs-Wellcome wanted only one thing," drug expert Joe Graedon says, and that was "to put the seizure problem behind them and persuade the FDA to approve Wellbutrin. I think they ignored Crenshaw's findings for fear of rocking the boat at the FDA."
In 1987, when Crenshaw's study was published, the Graedons publicized Wellbutrin's apparent pro-sexual (i.e. sex-enhancing) effects in their column. But few people noticed, least of all doctors, who continued to get writer's cramp from jotting SSRI prescriptions while largely ignoring an equally effective alternative that left sexuality intact -- or even improved it.
GlaxoWellcome spokeswoman Holly Russell says the company considered Wellbutrin an antidepressant, and was not particularly interested in its sexual effects beyond its low risk of sexual side effects. Once Wellbutrin was approved, company advertising simply said that compared with SSRIs, it was less likely to cause sex problems.
Wellbutrin languished both on pharmacy shelves and as a focus of research. But in the mid-1990s, as the predecessors of Viagra demonstrated the market potential of pro-sexual medications, researchers showed renewed interest in Crenshaw's report. In the past few years, several studies published in respected journals -- but ignored by the mass media -- have confirmed Crenshaw's findings and extended them.
In a 1997 report, published in Clinical Pharmacological Therapies, researchers at the University of Alabama at Birmingham gave 107 depression sufferers one of four antidepressants: Wellbutrin or three SSRIs -- Prozac, Paxil or Zoloft. Among those taking the SSRIs, 73 percent complained of sex-impairing side effects. Only 14 percent of the Wellbutrin group reported sex problems, while 77 percent said the drug "heightened sexual function."
That same year, in a pilot study at the Medical University of South Carolina in Charleston, eight people who complained of sex-impairing SSRI side effects were told to take a low dose of Wellbutrin in addition. After one month, half reported "marked improvement" in their sex problems. The results were published in Annals of Clinical Psychiatry.
In another 1997 study, reported in Journal of Clinical Psychopharmacology, researchers at Valparaiso University in Indiana gave Wellbutrin to 14 nondepressed diabetic men with erection problems caused by diabetes. After 10 weeks, they showed improved sexual functioning.
In a 1998 study, researchers at the State University of New York at Buffalo repeated the South Carolina study, but on a larger scale. They tested Wellbutrin as an antidote for SSRI-induced sexual impairment in 47 depressed individuals who were told to take the drug an hour or two before sex. Wellbutrin successfully reversed the sex problems in 66 percent of them. The only significant side effect was tremor (in 15 percent).
Wellbutrin watcher Joe Graedon found these studies tantalizing. "There was mounting evidence that Wellbrutrin has a significant pro-sexual effect for people with a variety of conditions. No other drug had ever done that."
But the studies also left him frustrated. "One key question remained unanswered: Is Wellbutrin truly sex enhancing? Or is its ability to improve sexual function simply a result of mood elevation in formerly depressed people taking a drug that didn't kill sexuality? No one had nailed that down."
This year, two studies have focused on this question by testing Wellbutrin as a treatment for sexual dysfunction in people not suffering from depression or any other serious medical condition. Both studies used placebos that looked identical to Wellbutrin pills so subjects could not tell the difference.
At Case Western Reserve University School of Medicine, a team led by R. Taylor Seagraves, M.D., a professor of psychiatry, gave Wellbutrin to 66 women, ages 23 to 65, who had experienced low or no libido for an average of six years. All 66 took a placebo for six weeks, then the drug for eight weeks. At the end of the placebo phase of the study, the group averaged 0.9 sexual encounters. But by the end of treatment with Wellbutrin, the figure had more than doubled to 2.3. Extent of sexual arousal also increased significantly, and number of sexual fantasies more than doubled (0.7 to 1.8). "Before starting treatment," Seagraves says, "100 percent of the women were dissatisfied with their level of sexual desire, but by the end of the [Wellbutrin] treatment phase, 40 percent reported feeling satisfied." The drug's only signficant side effects were insomnia (18 percent), tremor (6 percent) and rash (6 percent).
At the University of Alabama, in a study reported in the Journal of Sex and Marital Therapy, a team led by Jack Modell, M.D., a professor of psychiatry, worked with 30 adults (20 women, 10 men), ages 21 to 54, who complained of low libido, poor sexual satisfaction, difficulty reaching orgasm and, among the men, premature ejaculation and erection problems. The researchers asked the participants to have sex at least twice a week for the duration of the study, and to keep detailed diaries of their erotic experiences. For three weeks, the participants had sex with no treatment at all to establish sexual base lines. Then for three weeks, they took a placebo, followed by three weeks of Wellbutrin. The placebo improved sexual function over base line, but Wellbutrin treatment "significantly improved" sexual functioning over the placebo. The women recorded highly statistically significant improvement in ability to reach orgasm and orgasmic pleasure, and the men reported highly significant improvement in ability to raise and maintain erection and experience orgasm/ejaculation. The only sex problem that did not respond to Wellbutrin was the men's premature ejaculation . In addition to overall improvement in their sexual functioning, one woman reported the first orgasm of her life, and another woman experienced her first multiple orgasms. Wellbutrin side effects were mild -- some headache, anxiety, irritability and insomnia -- but no one dropped out because of them.
"In our study, Wellbutrin had a definite pro-sexual effect in people with sexual dysfunction," Alabama researcher Roberta May explains. "Our study -- and the others to date -- are not enough to establish Wellbutrin as a routine treatment for sex problems, but I see no reason not to try it. As medications go, it's a pretty benign drug."
The University of Minnesota's Coleman agrees: "There is now enough research to suggest that Wellbutrin might be a useful treatment for sexual dysfunction."
But David Rowland, coauthor of the Valparaiso University study of diabetic men, is more cautious. "I don't think there's enough evidence to warrant Wellbutrin as a treatment for sexual dysfunction. But I think it should be a strong contender for first-line treatment of depression because it causes fewer sex problems than the SSRIs."
According to May, patients on SSRIs who are suffering sex problems because of it can ask their doctors about using a low dose of Wellbutrin (75 milligrams) in addition to their SSRI two hours before sex to mitigate SSRI-induced sexual impairment. And if they switch to Wellbutrin, or add it to their treatment regimen, its side effects are likely to be similar to those caused by SSRIs. "But there's somewhat more likelihood of tremor," May explains. "The tremors usually go away after a while, but at first they can be scary."
Because Wellbutrin is already an approved antidepressant, doctors are free to prescribe it for sex problems without the FDA's specific approval. But approval would allow advertising and would certainly boost sales, especially to women, who have not shown benefit from Viagra, and to men with sex problems unrelated to erection, who also don't benefit from Viagra.
GlaxoWellcome's Russell says the company has no current plans to fund studies that might persuade the FDA to approve Wellbutrin as a treatment for sex problems. "But since Viagra, there's been more interest in treatments for sexual dysfunction. We funded both the Seagraves study at Case Western and the Modell study at Alabama. We might fund a few more. I just can't say at this time."
Joe Graedon doubts GlaxoWellcome will fund enough studies to illuminate the extent of Wellbutrin's pro-sexual action. "Wellbutrin has been around for a good 10 years," he explains. "It's getting to be an old drug. It's almost off patent. Drug companies rarely invest research dollars in drugs that are close to going generic, because the patent expires [and] they can't recoup their investment."
So far, Wellbutrin has not been studied in healthy people who are not depressed and don't have sex problems. As a result, there's no way to know if it's generally sex enhancing, or to use a somewhat more loaded term, an aphrodisiac. No one interviewed for this article called Wellbutrin an aphrodisiac. But some conceded that it might be.
"If it is," Joe Graedon explains, "you can't drop it into someone's martini and an hour later have them beg you for sex. It takes several weeks of regular use for Wellbutrin's pro-sexual effects to appear. At this point, it's most appropriate as a treatment for sex problems in those under the care of a physician or sex therapist."
But Graedon wishes someone would study the possibility that Wellbutrin might be a sex enhancer in healthy individuals. "If it turns out to be an aphrodisiac -- even one that takes several weeks to kick in -- it would almost certainly become a billion-dollar drug. It's a mystery to me why GlaxoWellcome has seemed so uninterested all these years."