David Baxter PhD
Late Founder
Antidepressant Use and Sexual Function: Treatment Strategies
February 26, 2007
Richard Balon, MD
Professor of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine
Introduction
At the beginnings of modern-era psycho-pharmacology, side effects of medications were an unpleasant reality and the evaluation of medications focused mostly on their efficacy. As psychopharmacology has become more refined, the focus on identifying side effects and efforts to minimize them have become more prominent.
Approaching Diagnosis of Sexual Dysfunction
Management of sexual dysfunction associated with antidepressants begins during the initial evaluation of a patient considered for medication treatment. A good initial evaluation should include a comprehensive sexual history and evaluation of current and premorbid sexual functioning. Many studies of sexual dysfunction associated with medications had a major methodologic flaw, which is also a clinical flaw; namely, lack of a baseline evaluation. An experienced clinician is aware of the fact that one cannot always rely on the patient?s memory. Asking the patient 4 weeks later whether he or she had any difficulties with erection or orgasm is not the best way to collect reliable information. The initial evaluation should also include an acknowledgment of the possibility of sexual dysfunction associated with medications and communication of this possibility to the patient.
There may be barriers or obstacles to an appropriate evaluation of sexual functioning. Patients may be hesitant to communicate intimate problems or may have misconceptions about adequate sexual functioning. Thus, questioning about sexual functioning should be sensitive but straightforward and focused. Questions such as ?How is your sex life?? are not very helpful. It is better to ask specifically about sexual desire, arousal, and experience of orgasm. Interestingly, physicians themselves may be a barrier to a good evaluation of sexual functioning, as they may feel uncomfortable with the topic or may mistakenly expect patients? discomfort with this topic.
A good baseline evaluation does not only provide the baseline data, but may also help the treating physician to select an appropriate sexual dysfunction management strategy. A patient who has never been treated with an antidepressant and for whom his or her undisturbed sexual functioning is quite important should probably be started on an antidepressant with a low incidence of sexual dysfunction. On the other hand, a patient who reports a history of sexual dysfunction with a particular antidepressant should probably not be started on that agent.
Management of Sexual Dysfunction Associated with Antidepressants
The main strategies for antidepressant-induced sexual dysfunction can be found in the table.
The first strategy is starting treatment with an antidepressant with a low prevalence of associated sexual dysfunction, such as bupropion, mirtazapine, and nefazodone (in some countries also moclobemide or reboxetine, neither available in the US). This could be useful for sexually active, medication-naive patients. A second strategy is waiting for spontaneous remission of sexual dysfunction, which requires a good deal of patience and a good doctor-patient relationship. The effectiveness is usually low. It has been reported that a substantial proportion of patients still report antidepressant-induced sexual dysfunction after several months of treatment with antidepressants. This strategy may be useful for patients with a low frequency of sexual activity. A third strategy is scheduling sexual activity around the dose of antidepressant, delaying daily medication intake after the sexual activity. This strategy may work for some of the short half-life antidepressants, but not much is known about its efficacy. A fourth strategy is reduction of dosage. This strategy may be especially useful in patients having other side effects as well. However, it may be risky. Patients may relapse if a subtherapeutic dose is reached. A fifth strategy is drug holidays. This strategy involves relatively brief interruption of treatment (eg, 2?3 days) with sexual activity scheduled for the end of this period of interruption. A variant of this approach is the partial drug holiday strategy, ie, lowering the dose of antidepressant for a brief period. This strategy poses several possible risks, such as relapse of depression, discontinuation syndrome in short half-life antidepressants, and encouragement of non-adherence.
A sixth strategy is switching to an antidepressant with a low rate of associated sexual dysfunction, such as bupropion, mirtazapine, and nefazodone (in some countries also moclobemide and reboxetine). This strategy has been described as one of the most effective ones. It should be used especially in relatively treatment-na?ve patients (the first or second antidepressant, not the fifth medication that finally helped with depression). The possible risks include relapse of depression and/or emergence of new side effects with the new antidepressant.
A seventh strategy involves use of so-called antidotes or other medications to alleviate sexual dysfunction. The list of antidotes which have been reported includes, but is not limited to, amantadine, bupropion, buspirone, cyproheptadine, dextroamphetamine, ephedrine, gingko biloba, methylphenidate, mirtazapine, pemoline, pramipexole, sildenafil, and trazodone. The usefulness of most of these antidotes has been reported in case reports or case series, and none of these substances has been Food and Drug Administration-approved for the treatment of sexual dysfunction associated with antidepressants.
Conclusion
Sexual dysfunction associated with antidepressants remains a complicated clinical problem. It may occur in up to 70% of patients treated with some antidepressants. The estimates of rates of antidepressant-associated sexual dysfunction are complicated by numerous factors such as the occurrence of sexual dysfunction associated with depressive and other disorders, some physical illnesses, medications, and substances of abuse. Studies of sexual dysfunction in general, sexual dysfunction associated with depression, and sexual dysfunction associated with antidepressants have been marred by numerous methodologic issues (unclear definition, lack of baseline assessment, lack of validated assessment tools), which even further complicate the estimation of prevalence of sexual dysfunction associated with antidepressants.
Although several management strategies for antidepressant-associated sexual dysfunction have been proposed, most experts would recommend as first-line approaches either starting treatment with an antidepressant with a low prevalence of associated sexual dysfunction or switching to this kind of antidepressant if sexual dysfunction with another antidepressant develops. Evidence from literature suggests that adding sildenafil, tadalafil, or bupropion may be useful in some sexual dysfunction associated with antidepressants. The treatment of this side effect should be individualized and still remains a clinical art rather than a science.
February 26, 2007
Richard Balon, MD
Professor of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine
Introduction
At the beginnings of modern-era psycho-pharmacology, side effects of medications were an unpleasant reality and the evaluation of medications focused mostly on their efficacy. As psychopharmacology has become more refined, the focus on identifying side effects and efforts to minimize them have become more prominent.
Approaching Diagnosis of Sexual Dysfunction
Management of sexual dysfunction associated with antidepressants begins during the initial evaluation of a patient considered for medication treatment. A good initial evaluation should include a comprehensive sexual history and evaluation of current and premorbid sexual functioning. Many studies of sexual dysfunction associated with medications had a major methodologic flaw, which is also a clinical flaw; namely, lack of a baseline evaluation. An experienced clinician is aware of the fact that one cannot always rely on the patient?s memory. Asking the patient 4 weeks later whether he or she had any difficulties with erection or orgasm is not the best way to collect reliable information. The initial evaluation should also include an acknowledgment of the possibility of sexual dysfunction associated with medications and communication of this possibility to the patient.
There may be barriers or obstacles to an appropriate evaluation of sexual functioning. Patients may be hesitant to communicate intimate problems or may have misconceptions about adequate sexual functioning. Thus, questioning about sexual functioning should be sensitive but straightforward and focused. Questions such as ?How is your sex life?? are not very helpful. It is better to ask specifically about sexual desire, arousal, and experience of orgasm. Interestingly, physicians themselves may be a barrier to a good evaluation of sexual functioning, as they may feel uncomfortable with the topic or may mistakenly expect patients? discomfort with this topic.
A good baseline evaluation does not only provide the baseline data, but may also help the treating physician to select an appropriate sexual dysfunction management strategy. A patient who has never been treated with an antidepressant and for whom his or her undisturbed sexual functioning is quite important should probably be started on an antidepressant with a low incidence of sexual dysfunction. On the other hand, a patient who reports a history of sexual dysfunction with a particular antidepressant should probably not be started on that agent.
Management of Sexual Dysfunction Associated with Antidepressants
The main strategies for antidepressant-induced sexual dysfunction can be found in the table.
The first strategy is starting treatment with an antidepressant with a low prevalence of associated sexual dysfunction, such as bupropion, mirtazapine, and nefazodone (in some countries also moclobemide or reboxetine, neither available in the US). This could be useful for sexually active, medication-naive patients. A second strategy is waiting for spontaneous remission of sexual dysfunction, which requires a good deal of patience and a good doctor-patient relationship. The effectiveness is usually low. It has been reported that a substantial proportion of patients still report antidepressant-induced sexual dysfunction after several months of treatment with antidepressants. This strategy may be useful for patients with a low frequency of sexual activity. A third strategy is scheduling sexual activity around the dose of antidepressant, delaying daily medication intake after the sexual activity. This strategy may work for some of the short half-life antidepressants, but not much is known about its efficacy. A fourth strategy is reduction of dosage. This strategy may be especially useful in patients having other side effects as well. However, it may be risky. Patients may relapse if a subtherapeutic dose is reached. A fifth strategy is drug holidays. This strategy involves relatively brief interruption of treatment (eg, 2?3 days) with sexual activity scheduled for the end of this period of interruption. A variant of this approach is the partial drug holiday strategy, ie, lowering the dose of antidepressant for a brief period. This strategy poses several possible risks, such as relapse of depression, discontinuation syndrome in short half-life antidepressants, and encouragement of non-adherence.
A sixth strategy is switching to an antidepressant with a low rate of associated sexual dysfunction, such as bupropion, mirtazapine, and nefazodone (in some countries also moclobemide and reboxetine). This strategy has been described as one of the most effective ones. It should be used especially in relatively treatment-na?ve patients (the first or second antidepressant, not the fifth medication that finally helped with depression). The possible risks include relapse of depression and/or emergence of new side effects with the new antidepressant.
A seventh strategy involves use of so-called antidotes or other medications to alleviate sexual dysfunction. The list of antidotes which have been reported includes, but is not limited to, amantadine, bupropion, buspirone, cyproheptadine, dextroamphetamine, ephedrine, gingko biloba, methylphenidate, mirtazapine, pemoline, pramipexole, sildenafil, and trazodone. The usefulness of most of these antidotes has been reported in case reports or case series, and none of these substances has been Food and Drug Administration-approved for the treatment of sexual dysfunction associated with antidepressants.
Conclusion
Sexual dysfunction associated with antidepressants remains a complicated clinical problem. It may occur in up to 70% of patients treated with some antidepressants. The estimates of rates of antidepressant-associated sexual dysfunction are complicated by numerous factors such as the occurrence of sexual dysfunction associated with depressive and other disorders, some physical illnesses, medications, and substances of abuse. Studies of sexual dysfunction in general, sexual dysfunction associated with depression, and sexual dysfunction associated with antidepressants have been marred by numerous methodologic issues (unclear definition, lack of baseline assessment, lack of validated assessment tools), which even further complicate the estimation of prevalence of sexual dysfunction associated with antidepressants.
Although several management strategies for antidepressant-associated sexual dysfunction have been proposed, most experts would recommend as first-line approaches either starting treatment with an antidepressant with a low prevalence of associated sexual dysfunction or switching to this kind of antidepressant if sexual dysfunction with another antidepressant develops. Evidence from literature suggests that adding sildenafil, tadalafil, or bupropion may be useful in some sexual dysfunction associated with antidepressants. The treatment of this side effect should be individualized and still remains a clinical art rather than a science.
