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Ways to handle sexual side effects from SSRI's
Ways to handle sexual side effects from SSRI's
In the Lexapro discussion thread, I was mentioning that there are things you can try to deal with sexual side effects of SSRI's. I just found the article, written by Dr Michael Jenike, leading expert on SSRI's.
MANAGING SEXUAL SIDE EFFECTS
by Dr. Michael Jenike
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
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%
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,
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
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
It is now theoretically possible the new drug, Viagra, may also be
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.
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
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,
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,
Masand S, Reddy N, Gregory R: SSRI-induced sexual dysfunction
successfully treated with amantadine. Depression 2:319-321,
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,
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".