In part one of this two-part series, we learned that sexual side effects from many of the "new generation" antidepressants are quite common. In part two, we’ll talk about why these problems are overlooked and some of the strategies that have evolved for their management.

Sexual difficulties such as loss of desire, inability to achieve orgasm or ejaculate, and problems with penile erection and vaginal lubrication, are common side effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin/norepinephrine reuptake inhibitors (SNRI). An important new study of antidepressant-induced sexual dysfunction in 6,297 patients found that 40% experienced sexual side effects from the top four SSRIs and two SNRIs.

Sexual side effects are an important concern in antidpressant therapy because they can cause the patient to stop taking his or her medication, thus jeopardizing the prospect for effective management of depressive illness.

A difficult diagnosis

One of the challenges of treating sexual dysfunction in patients with depressive illness is determining the cause of the problem. Before the patient’s sexual dysfunction can be attributed to antidepressant therapy, a number of other possibilities must be considered. Normal sexual function can be disrupted by any of the following:

1. The underlying depressive illness itself.

2. Other illnesses, such as diabetes; various infections; endocrine disorders; and renal, hepatic, neurologic, or cardiovascular disease.

3. Drugs other than antidepressants, including antiandrogens; blood pressure medications; other psychoactive drugs; histamine-receptor blockers like Tagamet; alcohol; tobacco; and marijuana, heroin, and methadone.

4. Past surgical procedures.

5. Nutritional deficiencies.

6. Relationship problems.

Identifying the cause of the patient's sexual problem(s) would be simpler if physicians conducted a baseline assessment of the patient's sexual function prior to initiating SSRI therapy. SSRI-induced sexual dysfunction may occur as soon as seven days after the drug is prescribed. Another clue to diagnosis is that SSRI-induced sexual dysfunction is usually generalized, meaning it occurs in all situations--so if the patient reports normal orgasm with masturbation but inability to have an orgasm with a partner, this is highly suggestive of a relationship problem rather than an "organic" cause.

Out of sight, out of mind?

Further confounding the treatment of antidepressant-induced sexual dysfunction is the simple fact that doctors and patients are generally reluctant to raise sexual issues. The doctor doesn’t ask, and the patient doesn’t tell. In one study of sexual dysfunction related to SSRIs, 58% of 344 SSRI patients reported some form of sexual dysfunction. Remarkably, however, it was only after direct questioning about specific sexual problems that this rate came to light; prior to questioning, only 14% volunteered that they were experiencing such problems.

Strategies for medical management

A number of strategies have evolved for the management of antidepressant-induced sexual dysfunction.

Wait and see -- The first principle is not to disrupt successful treatment of the underlying depressive illness, and to this end, the most conservative approach is to wait four to six weeks for the problem to resolve on its own. However, if the problem fails to resolve or has already persisted for some time, a more aggressive approach is indicated. The wait-and-see approach requires the consent and cooperation of the patient; otherwise, the patient may unilaterally decide to discontinue therapy

Dose reduction -- SSRIs have what is known as a flat dose-response curve, meaning that the same therapeutic effect can be achieved with a relatively wide range of doses. Thus, it may be possible to lower the dose of the SSRI without causing the patient’s depressive illness to reappear or worsen. It may also be possible to arrange the timing of doses such that the usual time of sexual intercourse coincides with the time of lowest daily SSRI drug levels in the body.

Drug discontinuation -- With SSRIs that are cleared from the body relatively rapidly, like Zoloft and Paxil, a two-day "drug holiday" involving the discontinuation of drug therapy is sometimes successful. This typically involves stopping therapy on Thursday night and resuming dosing on Sunday morning. Patients should be advised that discontinuing an SSRI is sometimes associated with withdrawal side effects, including fatigue, muscle pain, and unpleasant sensory disturbances.

Medical therapy -- Another approach is to co-medicate with an antidote to the sexual side effect. Successful reversal of SSRI-induced sexual dysfunction has been reported with amantadine, bupropion, buspirone, cyproheptadine, pemoline, and yohimbine. Patients with erectile dysfunction may also benefit from Viagra (sildenafil).

Change medications -- It is possible to switch to another antidepressant that does not cause sexual side effects. In a recent study of 6,297 patients taking an antidepressant, Wellbutrin (bupropion) and Serzone (nefazodone) were found to be significantly less likely to cause sexual side effects than SSRIs or SNRIs. Bupropion has been used successfully to treat women with hypoactive sexual desire disorder unrelated to antidepressant therapy.

Candidates for antidepressant therapy who have active sex lives may be better served by starting therapy with one of the newer antidepressants that has only minimal sexual side effects, such as Serzone or Wellbutrin.

Conclusion

There’s no question that SSRIs and SNRIs have improved the treatment of depressive illness. But every rose has its thorns, and in the case of this new generation of antidepressants, one of the larger concerns is the potential for sexual side effects. Drug-induced sexual dysfunction can lead a patient to stop using an antidepressant that is otherwise successful at managing the patient’ illness. Alternative medications like bupropion and nefazodone may solve the problem for some patients, but no drug, of any type, is 100% effective in 100% of patients. Fortunately, a range of alternative approaches exists.