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Archived Questions
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Sexual Side Effects of SSRIs
I am treating a depressed elderly man with paroxetine (Paxil ®). He reports that he is experiencing improvement in mood, energy and other symptom areas but at the same time has developed a marked decline in libido. |
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I have heard that SSRIs such as Paxil® can cause significant sexual side effects. Should I switch antidepressants? If so, to what?
I am glad you asked this question. Too often, sexuality in the elderly is simply ignored by physicians, and patients themselves may feel too embarrassed to initiate the discussion.
In elderly patients with depression, sexual functioning can be adversely affected by depression itself, age, and a number of comorbid conditions, including cardiovascular disease, hypertension, obesity, hyperlipidemia, and diabetes. Thus, it can be sometimes difficult to attribute sexual dysfunction directly to antidepressant side effects, but for the patient you mention, it is fairly clear from the history that this is a drug effect. It may also be true that older patients or those with comorbid vascular conditions are more sensitive to antidepressant-related sexual side effects, but this has not been clearly established.
I promise to answer your question directly, but first consider this: We know that serotonin in general tends to inhibit sexual functioning in both men and women. This is admittedly an oversimplification, since stimulation of some of the 7 different post-synaptic serotonin receptors, especially the 5HT2 receptors, increases thresholds for stimulation and arousal in men and women and erection and ejaculation in men, whereas stimulation of other serotonin receptors, for example, 5HT1A, actually lowers these thresholds. Still, the generalization stands. SSRI antidepressants, such as fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), and escitalopram (Lexapro®), as well as the SNRI antidepressant venlafaxine (Effexor®), to varying degrees, all have an inhibitory effect on sexual functioning. In contrast, dopaminergic neurotransmission, in general, tends to lower the threshold for sexual arousal, stimulation, erection, and ejaculation.
Thus, mixed mediator nonserotonergic antidepressants that block specific post-synaptic serotonin receptors (e.g., 5HT2 ) are thought to be the best choices to avoid antidepressant sexual side effects. This category would include nefazodone (Serzone®) or mirtazapine (Remeron®). Also, drugs that primarily increase norepinephrine or dopamine neurotransmission, such as bupropion (Wellbutrin®) or the tricyclic antidepressants as a class, would also be less likely than SSRIs to cause sexual side effects. If for other reasons you prefer to prescribe an SSRI , then agents such as paroxetine, which lack any significant effect on dopamine, should be avoided in favor of serotonergic drugs with a slightly more balanced profile of serotonergic and dopaminergic enhancement, such as sertraline.
Although the literature does not support switching from SSRIs to drugs such as nefazodone, mirtazapine or bupropion to reverse drug-related sexual dysfunction, possibly because of the confounding effect of depression itself on sexual functioning, this still seems to make compelling clinical sense in some situations. In making this switch, it is important to taper the SSRI to avoid serotonin withdrawal syndrome; this is less important with fluoxetine, which has a longer half-life than the others. In these situations, I usually introduce the new drug before completely stopping the old in order to avoid a "trough" effect in which the patient is subject to depressive relapse.
Would you recommend the use of Viagra® for serotonin-related sexual side effects?
The efficacy of sidenafil (Viagra®) in the treatment of serotonin-related erectile dysfunction has now been fairly well established, although the relevant studies did not include many patients over the age of 70. Sidenafil and its new, faster-acting variant, vardenafil (Levitra®), and new longer-acting variant, tadalafil (Cialis®), all work by inhibiting phospodiesterase-5, which prolongs relaxation of penile smooth muscles, allowing for more sustained retention of blood. None of these drugs seem to interfere with the antidepressant effect of the serotonin drugs. The most common side effects are headache and flushing, but particular caution must be taken in elderly patients with cardiovascular disease or who have significant hypertension or hypotension.
Unfortunately, there is no indication for the use of sidenafil, vardenafil, or tadalafil to relieve serotonin-related sexual side effects other than erectile dysfunction, since these drugs simply enhance a naturally-occurring phenomenon, that is, are effective only in the context of active sexual desire. Nevertheless, some physicians are offering anecdotal reports of efficacy in the "off-label" indication of serotonin-mediated loss of libido. However, I cannot recommend doing this.
Would you consider using testosterone for elderly men on antidepressants who complain of a decline in sexual functioning?
Hormone replacement is being studied in some centers, although not specifically with subjects taking antidepressant medications. Since the primary etiology of erectile dysfunction in elderly men is vascular, androgen administration has no obvious theoretical rationale for that particular symptom. Yet because male hypothalamic-pituitary-gonadal functioning declines with age, interest remains for using testosterone for age-related declines in sexual stimulation and arousal. However, there is insufficient information on the safety and efficacy of such treatment, especially when antidepressants are given concurrently, to recommend it at the present time.
Do you have ideas for further reading on this topic?
Suggestion for further reading:
Nurnberg, HG, guest editor: Erectile dysfunction and comorbid depression: prevalence, treatment strategies, and associated medical conditions. Journal of Clinical Psychiatry 64:Suppl 10, 2003.
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