From the March/April 1999 issue
As a psychiatrist and couples therapist, some days it seems as if I never talk about anything but sex. And increasingly, I find myself educating my patients about the impact of the new selective serotonin reuptake inhibitors (SSRIs) on sexual interest and pleasure. Sure, I’ve had patients blush or change the topic, but most welcome the invitation to discuss problems in their sex lives, some related to medication, others not.
I didn’t used to talk so much about sex and the sexual side effects of antidepressant medications. When I started practicing psychiatry a dozen years ago, we weren’t yet in the better-sex-through-modern-chemistry era. Then the landscape changed. We began to live and practice in a culture that has come to consider pharmacology an acceptable (if not ideal) means of reducing depression. But until we had some ideas about how to counteract the sexual side effects of antidepressants, it still didn’t much matter whether we talked about them or not.
Things are different now. We know that sexual side effects are among the most common and most troublesome difficulties experienced by antidepressant consumers. And more important, I know that I usually can help my patients recover from debilitating depression or anxiety without paying a sexual price.
When Prozac first came on the market, the medical profession didn’t have a clue about how vital serotonin was to sexual pleasure and responsiveness. We didn’t realize that Prozac and its two bestselling counterparts, Paxil and Zoloft, can and often do greatly reduce human suffering, but they also frequently kill sex drive, cause delayed ejaculation or completely eradicate orgasms. To this day, the Physician’s Desk Reference (PDR) grossly underestimates the rate of sexual dysfunction caused by SSRIs. The PDR lists an incidence rate of medication-induced sexual dysfunction in the range of two percent or less. Would that this were true! In reality, between one third and one half of all individuals taking the most commonly prescribed antidepressants experience sexual side effects. And these three drugs–Prozac, Paxil and Zoloft–are among the top 10 most common prescriptions written in the United States for any condition–affecting, literally, millions of Americans.
The target of antidepressants are the neurotransmitters, our brains’ chemical messengers. But neurotransmitters like serotonin are also found outside the brain wherever there are small blood vessels, a fact that accounts for many of the common side effects of SSRIs, such as nausea or jitteriness. Because serotonin is a sexually inhibitory neurotransmitter, increased serotonin in the brain may curtail the urge to have sex. Outside of the brain, serotonin may reduce genital sensation, somewhat like a mild anesthetic: what used to feel great feels good, what used to feel good feels okay, and what used to feel okay doesn’t even register now. This means that arousal, both the psychological interest and physiological blood vessel reaction (blood flow to the clitoris, while less obvious, is as important for pleasure for females as blood flow to the penis is for males), may be suppressed by antidepressants that increase serotonin. Clinically, this translates into any combination of possibilities: lack of interest in sex, difficulty reaching an orgasm or outright absence of orgasm, inability to maintain an erection or prolonged erection. Some individuals experience a variety of side effects, while others experience only one, in an unpredictable fashion. And of course, it’s just common sense that if you can’t have an orgasm, eventually the libido falters as a consequence.
The chart below summarizes the degree of sexual side effects likely to be caused by the most frequently prescribed antidepressants.
Prevalence of Sexual Side Effects Caused by Antidepressants
High Incidence
Anafranil (clomipramine)
Effexor (venlafaxine)
Luvox (fluvoxamine)
Monoamine oxidase inhibitors (Nardil, Parnate)
Paxil (paroxetine)
Prozac (fluoxetine)
Zoloft (sertraline)
Moderate Incidence
Elavil (amitriptyline)
Norpramin (desipramine)
Pamelor (nortriptyline)
Tofranil (imipramine)
Sinequan (doxepin)
Other tricyclics
Low Incidence
Desyrel (trazodone)
Remeron (mirtazapine)
Serzone (nefazodone)
Wellbutrin (bupropion)
Xanax (alprazolam)
Klonopin (clonazepam)
One common intervention for any SSRI-induced sexual side effect is simply to lower the dose, as long as effective treatment for the psychiatric condition can be maintained. Since arousal, erection and orgasm changes are all dose-related phenomena, a substantial number of people will continue to benefit emotionally from smaller amounts of the offending SSRI. However, lowering the dose always carries the risk of a symptomatic relapse, and should symptoms exacerbate following dose reduction, other strategies are necessary.
Some people will benefit from a so-called “drug holiday” (an intervention that does not work for Prozac, due to the much longer time that Prozac remains in the bloodstream, compared with the shorter-acting SSRIs). A physician might recommend a regular drug holiday, in which the medication is taken on Thursday morning, skipped on Friday and Saturday, and resumed on Sunday morning. Ideally, a couple would opt to make love first thing Sunday morning, but many couples would find that a Saturday-night schedule is preferred.
Should these more conservative measures fail (or be clinically inappropriate in the prescribing physician’s or patient’s view) there are other options. Three of the new antidepressants—Wellbutrin, Serzone and Remeron—have no sexual side effects at all. Wellbutrin is generally well tolerated, but may cause insomnia, headache, tremor or increased anxiety. Its major drawback is that it is only effective for depression and may exacerbate conditions such as panic disorder. Wellbutrin is pharmacologically distinct from the SSRIs in that it enhances the neurotransmitter dopamine rather than serotonin. As a result, while it has comparable efficacy for depressive disorders in general, any particular individual may respond preferentially to an SSRI (or vice versa).
Both Serzone and Remeron are very sedating, although this effect often wears off over time, especially for Remeron, which is taken at bedtime. However, Serzone must be taken in the morning as well, and sedation is a troublesome side effect for many. Remeron’s major drawback is the high incidence of weight gain, a side effect far less tolerable in many cases than low libido.
The tricyclic antidepressants, such as Elavil, Norpramin, Pamelor and Tofranil, may cause sexual side effects, including erectile or arousal problems and anorgasmia. Nevertheless, the incidence is far lower than with the SSRIs. The major drawback to tricyclic antidepressants is their potentially negative cardiac effect, elevating the risk of suicide and overdose. Higher doses may cause sedation, constipation, dry mouth and weight gain. Tricyclics have a particular utility for panic disorder, since lower doses than those needed for depression may be effective, allowing a mid-range dose that causes neither sexual dysfunction nor other significant side effects. Antianxiety medications, such as Klonopin and Xanax, do not affect serotonin and do not have sexual side effects as a rule.
Finally, some physicians may recommend St. John’s wort, which is not believed to cause sexual side effects, although this has not been systemically studied. Unfortunately, because St. John’s wort is not regulated as a pharmaceutical substance, efficacy may vary widely among preparations, and even from one bottle of the same brand to the next. This, along with the fact that it has not been rigorously tested in head-to-head comparisons with traditional antidepressants (for efficacy and also for side effects), limits its use to mild cases of depression or anxiety. St. John’s wort should be taken three times per day and many people have a problem remembering the midday dose.
If switching to an alternative medication is not clinically appropriate or effective, a physician might recommend adding another medication on a daily or as-needed basis. Taking a second medication may be problematic on several counts. Women often feel awkward about actively seeking sexual pleasure. Many people also are extremely hesitant to take anything for depression, let alone two drugs. For others, a second medication offers a wonderful antidote to the side effects of an otherwise helpful medication.
Most commonly, psychiatrists prefer a single low dose of Wellbutrin for patients complaining of sexual side effects from other antidepressants. It is prescribed initially only as needed, but daily if required. This comedication strategy employs lower doses of Wellbutrin than would be necessary to treat depression. Pharmacologically, Wellbutrin enhances dopamine, which has the opposite effect on libido and orgasm of serotonin. Small doses may restore the serotonin-dopamine balance, alleviating sexual side effects.
The list of agents used to comedicate for sexual side effects include stimulants such as Ritalin (methylphenidate), Urecholine (bethanechol), Yocan (yohimbine), Symmetrel (amantadine) and Periactin (cyproheptadine). Anecdotal evidence suggests that the botanical preparation ginkgo biloba may reverse libido, arousal and/or orgasm problems. Anecdotal reports also suggest that Viagra (sildenafil) is effective for SSRI-induced absence of orgasm–even in women–but its use may be limited by cost ($9 per pill).
At times, it’s easy to distinguish whether sexual problems are a relationship issue or are caused by side effects. SSRI-induced sexual dysfunction follows a typical pattern: it begins within days or weeks of starting the new medication. For example, soon after she began taking Prozac for obsessive-compulsive disorder, Maria found she could no longer reach climax with her husband, Steve. She did not volunteer this information, which is one reason I routinely ask women about inability to orgasm. My male patients can tell me that “things aren’t working right sexually,” without having to look me in the eye and complain that sex is no longer pleasurable. Many women, however, experience an ambivalence about whether nice girls are allowed to like sex or should just go along with it. And some women are terribly embarrassed to talk about orgasms. “He could stand on his head and nothing happens” is Maria’s euphemistic description of her sexual difficulty. “It’s like a switch turned off down there.” Maria hasn’t talked about this with Steve, and I suggest that she let him know that medication is the problem, since he may be wondering if it’s his “fault.” Maria looks horrified at the thought, so I give her some written information to hand him.
I invite Maria to bring her husband to a session so that we can talk this over together. In our joint session, I explain that she is on a high dose of an SSRI for Obsessive-Compulsive Disorder, an illness that only responds to serotonin enhancing antidepressants. Because an SSRI is the only reasonable medication, switching to something like Wellbutrin isn’t an option. Further, I explain to her that since effective doses of SSRIs are typically higher for OCD than for depression or panic disorder, lowering the dose isn’t a good idea. Likewise, the drug-holiday approach isn’t appropriate for Maria. This leaves co-medication, an idea that Steve likes a lot more than does Maria.
Steve reveals that he feels so selfish since Maria stopped having orgasms, and he would like things to be the way they were before. He feels that he is imposing on Maria, because these days, he’s the only one reaching a climax when they make love. Somewhat reluctantly, Maria agrees to try comedication and I review the alternatives. Does trying something just when needed prior to intercourse seem best, or would a regular daily comedication be better? I explain that the only-when-needed medication is like a diaphragm–you lose spontaneity, but you don’t have to ingest it all the time. When I mention that the only “natural” remedy I know of that may alleviate inability to orgasm requires daily use, however, Maria jumps at this, stating that she’d rather take something natural even if it means taking it every day. I tell her about ginkgo bilboa, which she purchases at her health food store. Six weeks later, she reports that “it’s not like fireworks or anything, but it’s lots better. Steve says thank you.”
Maria remains reluctant to “own” sexual pleasure, continuing to describe her medication-induced sexual side effects– and return of orgasms–as Steve’s issue. Until Prozac came into her bedroom, Maria’s unexamined belief was that Steve mostly cared about his own pleasure, and that she was just there fulfilling her wifely duties. Now she’s heard from Steve loud and clear that her sexual pleasure is an integral part of his pleasure. A seed has been planted. For the first time, she and her husband have discussed their sexual relationship openly, and she has an opportunity to reframe her sexual self-image.
Valerie Davis-Raskin, MD, is the director of academic psychiatry at MacNeal Hospital in Berwyn, Illinois, and a clinical associate professor of psychiatry at the University of Chicago. She is the author of When Words Are Not Enough: The Women’s Prescription for Depression and Anxiety and coauthor with Karen Kleiman, MSW, of This Isn’t What I Expected: Overcoming Postpartum Depression.
