The Effects of Antidepressants on
Human Sexuality: Diagnosis and Management

Dr.Joe's Data Base

By Richard Balon, MD

KEY POINTS

o · Drug holidays in which the antidepressant is discontinued 2 to
3 days prior to sexual activity is more successful with drugs
that have a short half-life.
o · Clinicians should ask specifically about sexual desire, sexual
enjoyment, erectile problems, erections unrelated to sexual
activity, capacity to reach orgasm, changes in capacity to reach
orgasm, and painful orgasm.
o · Antidepressants also have been used to treat some sexual
dysfunctions, such as premature ejaculation.

OUTLINE
Introduction
Diagnosis of Sexual Dysfunction
Management
Reduction to the Minimal

* Effective Dosage
* Drug Holidays
* Switching to Another Antidepressant
* Using Secondary Pharmacologic Agents
* Vacuum Erectile Devices
* Matching Therapy to Type of Sexual Dysfunction

Positive Effects of Antidepressants on Sexual Function
Conclusion
Glossary
References
About the Author

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Introduction

Tricyclic antidepressants and monoamine oxidase inhibitors
(MAOIs) have been used in psychiatry and other disciplines for
almost 4 decades. Antidepressants were originally reserved for
serious cases of depression. Selective serotonin reuptake
inhibitors (SSRIs) were introduced into clinical psychiatry about
10 years ago. The use of SSRIs, along with advances in clinical
psychopharmacology research and the decrease in payments for
psychotherapy by third-party payers, have to some extent
revolutionized the field of clinical psychopharmacology. Since
these times, psychiatrists and primary care doctors have started
to treat disorders that were once considered the domain of
psychotherapy, such as dysthymia and some anxiety disorders, with
antidepressants.

We have been treating patients mostly in the outpatient setting.
The results of well-designed, long-term studies have helped to
define the duration of treatment of an episode of depression.1,2
We now continue antidepressant treatment for about 6 months
following remission, using the dosage that was effective in the
acute phase. Clinical psychopharmacologists have also become more
aware of various side effects, reasons for noncompliance, and
quality-of -life issues during treatment with antidepressants.
One such side effect is sexual dysfunction. Changes in sexual
functioning can occur with various mental disorders, such as
depression, and can also result from antidepressant therapy (see
Table 1).

The effects of psychotropic medication on sexual functioning have
been the subject of various excellent reviews.3-6 Drugs used for
treating depression have been implicated in sexual dysfunction
with increasing frequency, and changes in sexual functioning have
been reported with almost all the antidepressants (see Table 2).

Estimates of the incidence of treatment-emergent sexual
dysfunction with antidepressants vary from 1.9% (Physicians Desk
Reference, for fluoxetine) to over 90% (see Table 3). This vast
range is probably at least partially a reflection of the lack of
attention to sexual side effects in previous studies and the lack
of thorough and uniform methodology in current studies focused on
sexual dysfunction caused by antidepressant therapy. The majority
of studies have been nonsystematic. For example, some described
sexual dysfunctions that were reported spontaneously, some
described sexual dysfunction after patients were asked about it
in a systematic way, and some studies used questionnaires.
Frequently, changes in sexual desire were not elicited. Serial
questioning about sexual dysfunction during the course of
pharmacotherapy has also not been used.

Our understanding of the biology of normal sexual functioning and
of mechanismsof action of antidepressant-induced sexual
dysfunction is rather poor. Various neurotransmitter systems
(adrenergic, dopaminergic, serotonergic, muscarinic) seem to be
involved in the biology of normal sexual response and activity,
centrally and peripherally.3,5 None of these systems should be
solely implicated, and interactions on central and peripheral
levels are likely. Some other neurotransmitters, such as
acetylcholine, probably play a mediating role as well.5
Interestingly, a correlation between sexual dysfunction and the
anticholinergic effects of antidepressants was not observed in
one study.11 Sexual hormones and other substances (eg, vasoactive
intestinal peptide) probably have at least a modulating role.
Administration of drugs influencing various neurotransmitter
systems, such as antidepressants, could affect sexual functioning
in different ways. Various sexual dysfunctions are the most
frequently observed effects, but occasional improvement of sexual
functioning with antidepressants14 or unusual sexual
experiences15 have been reported. Antidepressants also have been
used to treat some sexual dysfunctions, such as premature
ejaculation.16 Obviously, antidepressants can cause various
changes in sexual functioning (see Table 4).

Sexual dysfunction has been a frequently mentioned cause of
noncompliance with antidepressant therapy, but this issue has not
been systematically studied. Rabkin et al17 reported four cases
of discontinuation of monoamine oxidase inhibitors (MAOIs), but
only one case was solely due to sexual dysfunction, without any
other major side effects. Other reports of noncompliance because
of sexual dysfunction are anecdotal. Nevertheless,
antidepressant-induced changes in sexual functioning pose a
difficult and interesting clinical problem, in part because of
the possibility of noncompliance.

Diagnosis of Sexual Dysfunction

The first two steps in the management of sexual dysfunction are
(1) recognition or identification of the dysfunction, and (2)
patient education. A baseline assessment of sexual functioning is
absolutely necessary. Without this there is nothing with which to
compare recent sexual functioning, and the clinician is unable to
determine accurately if the dysfunction is a new or an old
phenomenon.

As shown in Table 1, various factors can contribute to sexual
dysfunction; therefore, sexual dysfunction should not always be
attributed to medication. It may be a component of depressive
symptomatology (decreased libido); it may be due to concomitant
medical illness (impaired erectile capacity may be the first
symptom of diabetes mellitus); it may represent primary sexual
dysfunction (sexual desire disorders, sexual arousal disorders,
orgasmic disorders, sexual pain disorders); or it may be a side
effect of medication. Ruling out all other causes before
attributing the dysfunction to medication seems to be a prudent,
but not always practiced, approach. Given the multiple possible
sources of sexual dysfunction, caution should be used when
determining etiology.

Skilled clinicians should ask very specific questions. General
questions such as "How is your sex life?" are not enough because
they often lead to nonspecific answers such as "All right," "OK,"
"No problem." These answers will not provide adequate baseline
information for the assessment of possible future dysfunction.
Clinicians should ask specifically about sexual desire, sexual
enjoyment, erectile problems, erections unrelated to sexual
activity, capacity to reach orgasm, changes in capacity to reach
orgasm, and painful orgasm. It is known that asking about sexual
dysfunction elicits twice the incidence found when no questions
are asked. A good psychosexual history should be a part of every
initial evaluation.
Identification of antidepressant-induced sexual dysfunction can
be a diagnostic challenge. Is the problem a true sexual
dysfunction or has the patient mislabeled it? What type of
dysfunction is involved? Is it a single dysfunction or a
combination of dysfunctions? If a combination, which dysfunction
is primary? Is the problem generalized or situational? Is it the
result of a combination of medications? What is the patient's
reaction to the dysfunction? Were comorbid conditions, substance
abuse, and relationship problems considered?

Occasionally, other diagnostic procedures, such as physiologic
tests of erectile capacity (nocturnal penile tumescence, visual
stimulation method), tests of penile vascular competence,
neurologic evaluation, and hormonal assessment, must be used.

Patient education about possible sexual dysfunction can be
problematic. A good physician-patient relationship plays a
significant role. Some clinicians advocate either no discussion
of possible sexual dysfunction or a discussion with little
emphasis on dysfunctions and their severity, because they do not
want to discourage patients. However, some patients may be
informed about this topic because of increased attention by the
media or because of aggressive marketing strategies used by the
pharmaceutical companies. Oc-casionally, pharmacists may discuss
various side effects of antidepressants, including sexual
dysfunction, with patients, or other patients share their
experiences. At least some discussion of these problems is better
than no discussion. Clinicians should also mention that various
management options for antidepressant-induced sexual dysfunctions
are available.

Management

Once the diagnosis of sexual dysfunction induced by an
antidepressant is established, the clinician should carefully
consider management options (see Table 5) and discuss them with
the patient.
Waiting for Spontaneous Remission of Sexual Dysfunction
This might be considered a questionable approach. As with many
other side effects of antidepressants, spontaneous remission or
decrease in severity to a tolerable level is possible. Cases of
spontaneous remission have been reported for some
antidepressants, such as sertraline and phenelzine.18 However,
spontaneous remission may occur only after several weeks or
months, which may be too long for the patient to wait. This
approach requires a very good physician-patient relationship.
Also, it has not been reported to be effective for tricyclic
antidepressant-induced anorgasmia.5

Reduction to the Minimal

Effective Dosage

This approach may occasionally help, but it is also risky.
Balancing between the minimal effective dose and a subtherapeutic
dose can be precarious. The dose at which the dysfunction appears
is frequently the lowest that alleviates depression. Some authors
19 have suggested that there is a relationship between sexual
dysfunction and the dosage of fluoxetine. They observed an
improvement of sexual dysfunction and no recurrence of depression
when they decreased the dosage of fluoxetine to 20 mg every other
day, and in some cases to 20 mg a week. Sexual dysfunction
associated with venlafaxine also showed a dose relation in one
study.20 Despite the potential double-blind nature of dose
reduction, it has been frequently recommended in erectile
dysfunction.

Drug Holidays

A variant of dose reduction, the drug holiday approach
requiresthat the antidepressant be discontinued 2 to 3 days prior
to sexual activity. The success of this approach depends on
careful planning and a comfortable physician-patient
relationship. It is probably more successful with drugs that have
a short half-life, such as paroxetine and sertaline, and may be
difficult with long half-life drugs, such as fluoxetine. Again,
worsening of depressive symptomatology may complicate this
practical alternative for management of sexual dysfunction
associated with antidepressants.

Switching to Another Antidepressant

Several reports in the literature have described successful
substitution of desipramine for imipramine or clomipramine,
imipramine for amoxapine, and nortriptyline for imipramine or
doxepin. This approach may take a long time and its success may
be hindered by relapse of the depressive disorder.
Several studies report no sexual dysfunction with bupropion. In
one study,21 24 of 28 patients who reported sexual dysfunction on
various antidepressants reported resolution of their sexual
dysfunctions when switched to bupropion. Another study reported
significant improvement of fluoxetine-associated sexual
dysfunction in patients who were switched to bupropion.22
However, caution is needed because one unpublished report has
noted sexual dysfunctions in patients treated with the
sustained-release form of bupropion.23
With nefazodone, the newest antidepressant available in the
United States, there have been no reports of sexual dysfunction
to date, and in some clinical trials, the incidence of sexual
dysfunctions was found to be equivalent for nefazodone and
placebo.

Using Secondary Pharmacologic Agents

Numerous pharmacologic agents have been successfully used in the
"treatment" of sexual dysfunctions induced by antidepressants.
These include bethanechol (30 mg, 1 to 2 hours before coitus),24
cyproheptadine (4 to 12 mg, 1 to 2 hours before coitus; caution
patient that severe sedation or depression may occur),25, 26
yohimbine (5.4 mg tid or prn 2- to 4 hours before coitus; caution
patient that yohimbine may induce anxiety),9,27 neostigmine (7.5
to 15 mg, 30 min before coitus), amantadine (100 mg one or twice
daily up to 600 mg),28 bupropion (75 mg/day with fluoxetine),29
buspirone (30 mg/day or more with various SSRIs),30
dextroamphetamine (10 to 25 mg/day), and pemoline (18.75
mg/day).31 Other reportedly used agents include methylphenidate,
trazodone, and bromocriptine.

Vacuum Erectile Devices

Use of vacuum erectile devices and injection of agents into the
corpus cavernosum are specialized procedures that are best
handled by urologists.

Matching Therapy to Type of Sexual Dysfunction

There are various treatment strategies for different types of
drug-induced sexual dysfunction. In the case of decreased libido,
drug holidays, the addition of neostigmine, or the substitution
of another drug such as bupropion or nefazodone may be effective.
For erectile problems, dose reduction, drug holidays,
coadministration of bethanechol, or substitution of another drug
may be tried. Orgasmic dysfunction may be resolved by waiting for
spontaneous remission, or by drug holidays, coadministration of
another drug, or substitution of another drug.
Two important additional points are the following:
1. Only tentative conclusions about the efficacy of the above
treatments can be drawn because most of the literature in this
area consists of case reports or series of cases.6
2. Priapism (abnormal, persistent, usually painful erection
unrelated to sexual arousal) constitutes a urologic emergency.
Priapism has been reported with trazodone and various other
psychotropic drugs.

Positive Effects of Antidepressants on Sexual Function

Antidepressants do not necessarily adversely affect sexual
functioning. A few cases of "improved" sexual functioning have
been reported. Smith and Levitte reported a return of sexual
potency in three elderly men treated with fluoxetine.14 Others32
described an elderly male who developed "orgasmic sensations" on
fluoxetine. Orgasms associated with yawning in patients treated
with clomipramine and fluoxetine have also been reported.

Trazodone has been used to treat impotence. Lal and colleagues33
described the case of a psychiatrist who successfully treated his
own impotence with trazodone, 250 to 350 mg prior to coitus once
a week for 4 years. Montorsi and colleagues34 reported that the
combination of yohimbine (15 mg/day) and trazodone (50 mg/day) is
a safe and effective first-line treatment for psychogenic
impotence.

As already noted, one side effect of antidepressants ­p; delayed
or inhibited ejaculation ­p; has been used for treatment of
primary premature ejaculation. Some case reports have described
improvement of premature ejaculation with selective serotonin
reuptake inhibitors, such as sertraline35 and fluoxetine.36
Controlled studies have reported greater clinical improvement of
premature ejaculation with clomipramine compared with placebo37
(25 or 50 mg/day; the higher dose produced a longer time to
ejaculation), and paroxetine compared with placebo.16

Conclusion

The effects of antidepressants on human sexuality are complex.
The etiologic mechanisms of sexual dysfunctions are unclear and
intricate. The diagnosis and management of sexual dysfunction
induced by these agents is a challenging clinical issue requiring
a good physician-patient relationship, keen and skillful
observation, and a certain degree of creativity and patience.
Most effects of antidepressants on human sexuality are adverse,
but some effects are beneficial ­p; for example, antidepressants
can be used for the treatment of premature ejaculation.

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Glossary

Anorgasmia ­p; Inability to achieve orgasm, absence of orgasm.
Drug holidays ­p; Regular periods during which the patient is not
given medication.
Impaired erectile capacity ­p; Persistent or recurrent inability
to attain or to maintain an adequate erection, until completion
of the sexual activity.
Libido ­p; Sexual desire, drive, interest.
Priapism ­p; Persistent penile erection accompanied by severe
pain.
Primary sexual dysfunction ­p; Disturbance in sexual desire and
in the psychophysiological changes that characterize the sexual
response cycle causing marked distress. The term primarily refers
to etiology.

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Author

Dr. Balon is an associate professor of psychiatry and director of
medical student education in psychiatry in the Department of
Psychiatry and Behavioral Neurosciences at Wayne State University
School of Medicine in Detroit, Michigan.