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sexual side effects of Ssri drugs

MANAGING SEXUAL SIDE EFFECTS

Although the positive effects of SSRIs, clomipramine, and monoamine oxidase inhibitors are now well documented, there is a cost in terms of side effects. It is clear that more than 35% of patients on these drugs experience difficulties with sexual functioning. These problems usually involve diminished libido (although the opposite occasionally occurs) and/or orgasm problems in both sexes. In males, inability to maintain an erection or even complete impotence may occur.

If the clinician does not specifically ask about sexual difficulties, it may appear that they are quite rare since patients are often embarrassed or more commonly, they do not think to blame medication for these problems and may attribute them to difficulties in their relationships. Sexual difficulties may be an unspoken cause of treatment noncompliance, and knowledge of the patient_s sexual life may be a critical variable in drug compliance. To illustrate the magnitude of these problems, Montero (1987) studied clomipramine and found that 96% of patients who took the drug developed anorgasmia. However, when a sexual dysfunction questionnaire was given, only 36% of the 96% reported any type of sexual problem. When fluoxetine, sertraline, and paroxetine were first introduced, the reported incidence of sexual dysfunction was 2% to 9%; after careful questioning and better reporting of cases, the incidence is now 30% to 40%.

It is not completely clear what the mechanism of these sexual difficulties is, but most of the evidence for anorgasmia supports the hypothesis that increased serotonergic activity is inhibitory to ejaculation and orgasm. The various serotonin receptor subtypes may have different effects on sexual functioning; in particular, 5-HT2 receptors are probably inhibitory while other subtypes may be excitatory. This could account for the paradoxical effect of spontaneous orgasm in a small number of patients who have taken fluoxetine and clomipramine, even though both of these drugs cause extreme difficulty with ejaculation in the typical patient. These inconsistent effects may be explained by activation of certain receptors in some, but not all, patients (Seagraves et al, 1996).
The above effects can sometimes be reversed by medication like cyproheptadine, a drug with antiserotonergic action, as shown in a number of case reports (McCormick et al, 1990; Arnott & Nutt, 1994; Seagraves, 1991; Feder, 1991; Goldbloom & Kennedy, 1991) and in one double-blind study (Steele & Howell, 1986). However, cyproheptadine can reverse the antidepressant effects of SSRIs (Feder, 1991) and probably antiobsessional effects as well. In addition, it has significant sedative properties.

Recent reports (Norden, 1994; Seagraves et al, 1996) suggests that adding buspirone, a partial agonist of the 5-HT1A autoreceptor, may have a beneficial effect of decreasing or reversing sexual dysfunctions induced by SSRIs.

Yohimbine, an alpha-2 adrenergic antagonist, has also been reported to be helpful for anorgasmia precipitated by SSRIs. It is probably best not used in patients with comorbid panic disorder, excessive agitation, or hypertension (Seagraves, 1994; Seagraves et al, 1996).

Bupropion is thought to have a predominantly adrenergic mechanism of action, and it has been reported to be successful in reversing fluoxetine-induced anorgasmia. On interest, it has been found that bupropion increases the sexual fantasy life in a cohort of women with hypoactive sexual desire and that using the drug may also have a central effect that enhances libido as well as a peripheral effect that reverses SSRI-induced sexual dysfunction (Seagraves et al, 1996).

In various case reports, dextroamphetamine, methylphenidate (Bartlik et al, 1995), amantadine (Balogh et al, 1992; Balon, 1996; Masand et al, 1994-95), and even ginseng have all been reported as useful drugs for reversing anorgasmia (Seagraves et al, 1996).

Reynolds (1997) reported that nefazodone (Serzone), a drug with less than a 1% incidence of anorgasmia, partially reversed sertraline-induced anorgasmia in a 31-year-old man at a dose of 100 mg per day; lower doses were not helpful. At 150 mg taken 60 minutes before intercourse, he had a return of normal sexual functioning. At 6 months follow-up, the patient had no ill effects from the occasional addition of nefazodone to his continung sertraline therapy. Reynolds noted that nefazodone has a relatively short half-life of only 2 to 4 hours and reaches peak serum levels 1 hour after oral dosing.

A recent approach to the management of sexual difficulties involves the use of drug holidays where patients are allowed to omit medications on the weekends to allow sexual activity. This practice may work when drugs that have a short half-life, such as sertraline, paroxetine, clomipramine, and fluvoxamine are used, but will not work with drugs that have a very long half-life, such as fluoxetine.

A number of patients with drug induced sexual dysfunction can be helped by a little known technique of injection of the prostaglandin alprostadil into the corpus cavernosum of the penis (Caverject Upjohn). This can produce an erection in some men with erectile dysfunction. Most men claim that this injection with a small bore needle is almost painless. However, a recent report of using a p llet or microsuppository formulation that is used intraurethrally (MUSE [Medicated Urethral System for Erection] – Vivus) suggests that this technique may work as well without the need for injection This is marketed as a sterile foil pouch containing a pellet 1.4 mm in diameter and 3 or 6 mm long within the stem of a hollow applicator, which is inserted 3 cm deep into the urethra. Pressing a button pushes the pellet into the urethra. In a double-blind controlled trial, of 461 alprostadil-treated patients, 299 (65%) reported that they had achieved successful intercourse at least once, compared to
95 (19%) of 500 patients who inserted placebo pellets. Results were similar regardless of age or cause of impotence (Padma-Nathan et al, 1997). MUSE comes in four strengths that range in dose from $114 to
$138 for 6 units (The Medical Letter, 1997). The physician must determine the minimal effective dosage and check for hypotension before prescribing the drug for home use as there is about a 3% incidence of hypotension when the agent is first used.

In terms of patient management, some guidelines can be crystallized from the available literature. First, it is crucial to elicit a reasonable sexual history and ask directly about difficulties with libido (sexual drive), orgasm, erection, and satisfaction with sexual activity. Be clear with patients up front that antiobsessional and antidepressant medications are often associated with sexual difficulties. When identified, sometimes sexual problems can be lessened with simple dose reduction. Occasionally, these side effects diminish over time, but by no means in the majority of patients. Since there are now a number of effective antiobsessional drugs, it may be worth trying a switch to another drug, but if patients have had a good response, they may be reluctant to do this.
Patients may have sexual difficulties on one or two antiobsessional agents, and perform normally on others.

If for some reason you do not want to change medication, several possible antidotes exist. Yohimbine is useful for anorgasmia except in patients with panic disorder, excessive agitation, or hypertension and can be given at a dose of 10.8 mg (2 tablets) approximately an hour before intended intercourse. Others have recommended chronic use of yohimbine at 5.4 mg given three times a day (Seagra es et al, 1996). Cyproheptadine can also be used on an as needed basis, but it often puts patients to sleep. There is also the theoretical concern that it may reverse antiobsessional and antidepressant drug effects. Amantadine has been used on an as needed basis and may be worth a try. Bupropion, given at a dose of 75-100 mg daily may correct SSRI-induced sexual dysfunction. If for some reason the patient cannot tolerate bupropion, trazodone, 50-100 mg given daily can be used, especially for patients who have difficulties in developing and maintaining an erection (Seagraves et al, 199 ).

Sometimes combinations of these agents are used. For example, one report (Seagraves et al, 1996) advocated using bupropion starting at
37.5 mg given on a regular basis (not as needed) and increasing the dose to 75 mg daily, sometimes in combination with yohimbine 5.4 mg given daily. They also give methylphenidate 10 mg daily on occasion, with beneficial results. Others recommend pemoline instead of methylphenidate as an adjunct, because it often reduces orgasm problems and has a half-life of 10 to 12 hours.

Caverject and MUSE systems may be helpful for some patients. Drug holidays are being advocated more and more for the shorter acting agents.

There are recent reports that ginkgo biloba, a botanical derived from tree bark, may allow for better sexual functioning for people taking SSRI’s and other antidepressants. One article (Cohen, 1997) stated that “in an open trial of various formulations, ginkgo was found to be effective in 84% of patients with sexual dysfunction induced by antidepressants”.

It is now theoretically possible the new drug, Viagra, may also be useful.

Above all, it is important to note the empirical nature of treating sexual difficulties and the need for flexibility. Multiple approaches, including biological and psychosocial, in an alliance with the physician, patient, and sexual partner are required. There is no way to determine in advance which patients will have sexual difficulties and then which approach will help them function.
Several drugs and combinations may have to be tried. It is also important to monitor any concomitant medical problems or other medications that may have an effect on sexual functioning.

References

Monteiro WO, Noshirvani HF, Marks IM, et al: Anorgasmia from clomipramine in obsessive-compulsive disorder: A controlled trial.
Br J Psychiatry 151:107-112, 1987.

Seagraves RT, Thompson TL, Wise T: Sexual dysfunction and antidepressants. J Clin Psychiatry: Intercom: The Experts Converse.
August 17, 1996.

Seagraves RT: Reversing anorgasmia associated with serotonin uptake inhibitors [Questions and Answers]. JAMA 266:2279, 1991.

Seagraves RT: Treatment of drug-induced anorgasmia. Br J Psychiatry 165:554, 1994.

McCormick S. Olin J, Brotman AW: Reversal of fluoxetine-induced anorgasmia by cyproheptadine in two patients. J Clin Psychiatry 51:383-384, 1990.

Goldbloom DS, Kennedy SH: Adverse interaction of fluoxetine and cyproheptadine in two patients with bulimia nervosa. J Clin Psychiatry 52:261-262, 1991.

Feder R: Reversal of antidepressant activity of fluoxetine by cyproheptadine in three patients. J Clin Psychiatry 52:163-164, 1991.

Arnott S, Nutt D: Successful treatment of fluvoxamine-induced anorgasmia by cyproheptadine. Br J Psychiatry 164:838-839, 1994.

Steele TE, Howell EF: Cyproheptadine for imipramine-induced anorgasmia. J Clin Psychopharmacol 6:326-327, 1986.

Norden MJ: Buspirone treatment of sexual dysfunction associated with selective serotonin re-uptake inhibitors. Depression 2:109-112, 1994.

Masand S, Reddy N, Gregory R: SSRI-induced sexual dysfunction successfully treated with amantadine. Depression 2:319-321, 1994-95.

Balogh S, Hendricks SE, Kang J: Treatment of fluoxetine-induced anorgasmia with amantadine. J Clin Psychiatry 53:212-213, 1992.

Balon R: Intermittent amantadine for fluoxetine-induced anorgasmia.
J Sex Marital Ther (in press), 1996.

Reynolds RD: Sertraline-induced anorgasmia treated with intermittent nefazodone. J Clin Psychiatry 58:89, 1997.

Padma-Nathan H, et al. N Engl J Med. 336:1, 1997.

The Medical Letter. Intraurethral alprostadil for impotence.39:32, 1997.

Cohen A: authored a journal article in “Drug Topics”, 1997, Volume 141, page 33….entitled “BOTANICAL COULD IMPROVE SEX LIFE OF PATIENTS ON SSRI’s”.