Hostname: page-component-7479d7b7d-jwnkl Total loading time: 0 Render date: 2024-07-12T01:50:11.370Z Has data issue: false hasContentIssue false

Antidepressant drugs and sexual dysfunction

Published online by Cambridge University Press:  02 January 2018

David S. Baldwin*
Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton
Thomas Foong
Kirkstall Health Centre, Leeds, UK
David S. Baldwin, DM, FRCPsych, University Department of Psychiatry, College Keep, 4-12 Terminus Terrace, Southampton SO14 3DT, UK. Email:
Rights & Permissions [Opens in a new window]


Depressive symptoms and depressive illness are associated with impairments in sexual function and satisfaction but the findings of randomised placebo-controlled trials demonstrate that antidepressant drugs can be associated with the development or worsening of sexual dysfunction. Sexual difficulties during antidepressant treatment often resolve as depression lifts but may persist over long periods, and can reduce self-esteem and affect mood and relationships adversely. Sexual dysfunction during antidepressant treatment is typically associated with many possible causes, but the risk of dysfunction varies with differing antidepressants, and should be considered when selecting an antidepressant.

Copyright © Royal College of Psychiatrists, 2013 

There is a close relationship between the presence of depressive symptoms and reported sexual difficulties and dissatisfaction. Systematic reviews of the epidemiology of sexual difficulties, dysfunction and dissatisfaction indicate that sexual problems are common in men and women in all societies, and they are more frequent in older individuals and among those with chronic medical conditions, including depression.Reference DeRogatis and Burnett1,Reference Lewis, Fugl-Meyer, Corona, Hayes, Laumann and Moreira2 Recognising the strong association between sexual difficulties and the presence of depressive symptoms, an international consensus statement on sexual dysfunction in chronic illness recommends screening for depression.Reference Basson, Rees, Wang, Montejo and Incrocci3 Given its effects on mood, energy, interests and self-esteem, it should be expected that depression will lower sexual interest and satisfaction; and this is the case, more so in younger patients.Reference Hegeman, Kok, van der Mast and Giltay4 But depression may also exert adverse effects on other aspects of the sexual response including the ability to achieve and maintain penile erection or attain adequate vaginal moistening, ejaculation or orgasm, and distressing hypersexuality has also been reported.Reference Williams and Reynolds5 When considering the relative risks for and management of sexual dysfunction associated with antidepressant treatment, the adverse effects of depression itself and of any coexisting physical illness can be easy to overlook.

Relative incidence of sexual dysfunction during antidepressant treatment

Antidepressants have differing effects on sexual function, presumably due to variations in their pharmacological properties. Selective serotonin reuptake inhibitors may exert untoward effects on sexual functioning both through central (neurotransmitter)Reference Abler, Seeringer, Hartmann, Grön, Metzger and Walter6 and peripheral (neurotransmitter and vascular)Reference Frohlich and Meston7 effects. An early meta-analysis of studies with differing methodologies (including open-label, double-blind, cross-sectional, and retrospective investigations) suggests that sexual dysfunction is no more common with agomelatine, amineptine, bupropion, moclobemide, mirtazapine or nefazodone than it is with placebo, in contrast to the situation with other antidepressants.Reference Serretti and Chiesa8 A more recent meta-analysis of randomised controlled trials indicates that bupropion is associated with a lower rate of treatment-emergent sexual dysfunction than is seen with escitalopram, fluoxetine, paroxetine or sertraline;Reference Gartlehner, Hansen, Morgan, Thaler, Lux and Van Noord9 this is possibly due to the predominantly noradrenergic-dopaminergic mechanism of action of bupropion. A systematic review suggests mirtazapine is less likely than other antidepressants to cause adverse sexual effects, and this is probably due to its antagonist effects on the 5-HT2C receptor.Reference Watanabe, Omori, Nakagawa, Cipriani, Barbui and Churchill10 Randomised controlled trials with agomelatine suggest it has fewer adverse effects on sexual functioning than other antidepressants,Reference Hickie and Rogers11 which is more likely to be as a result of its antagonist effects on the 5-HT2C receptor rather than the agonist effects at melatonin receptors.

Assessing sexual functioning in patients with depression

Patients and health professionals alike can find it difficult to mention and discuss sexual symptoms, and reliance on spontaneous reporting of difficulties leads to a substantial underestimate of the prevalence of sexual problems.Reference Rizvi, Yeung and Kennedy12 Comprehensive assessment of a patient with depression reporting sexual difficulties while undergoing antidepressant treatment may be time-consuming, but can be facilitated through the use of screening or severity questionnaires, such as the Arizona Sexual Experiences Scale, Changes in Sexual Functioning Questionnaire, Psychotropic-Related Sexual Dysfunction Questionnaire and the Sex Effects Scale, although these cannot fully substitute for a sensitive but comprehensive interview.Reference Rizvi, Yeung and Kennedy12 Scales such as these have adequate psychometric properties (including validity, reliability and sensitivity to change) and so can be used to monitor sexual function and satisfaction prior to and during antidepressant treatment. There are many risk factors for development of sexual dysfunction (such as male gender, older age, lower academic achievement, lack of full-time employment, physical ill health, multiple drug treatment, excess alcohol consumption and troubled interpersonal relationships): but not all of these are amenable to intervention.

Improvement and deterioration of sexual function during antidepressant treatment

Reduction of depressive symptoms through successful antidepressant treatment can be accompanied by reported improvements in sexual desire and satisfaction.Reference Baldwin, Bridgman and Buis13 Many men troubled by persistent premature ejaculation can derive benefits from treatment with clomipramine or selective serotonin reuptake inhibitors, on either a daily or ‘as required’ basis.Reference Giuliano and Hellstrom14 However, antidepressant treatment is also associated with the worsening of pre-existing sexual dysfunction, and with the development of new sexual difficulties in previously untroubled patients. Incidence estimates vary widely, depending on the methodology used, but in excess of 45% of patients with depression may experience ‘treatment-emergent sexual dysfunction’ associated with antidepressant drugs.Reference Williams, Edin, Hogue, Fehnel and Baldwin15 Unfortunately, the long-term course of sexual dysfunction associated with antidepressant treatment is uncertain.

Management of sexual dysfunction in depression

The presence of antidepressant treatment-emergent sexual dysfunction can significantly reduce quality of life and self-esteem, and impose burdens on interpersonal relationships, over and above those associated with depression.Reference Williams and Reynolds5 Sexual dysfunction may also cause some patients to stop treatment, although the evidence for this is sparse. Many strategies have been proposed for managing patients troubled by sexual dysfunction associated with antidepressant drugs, but the number of randomised placebo-controlled trials is limited, and there is an absence of randomised controlled data evaluating the effect of psychological interventions.Reference Taylor, Rudkin and Hawton16

Choosing an antidepressant from the list of those regarded as having fewer adverse effects on sexual functioning is reasonable, if patients are concerned to preserve sexual functioning and when other considerations allow; but some of these antidepressants have other bothersome side-effects, limited availability or questionable efficacy. A reduction in daily dosage is a commonly adopted first-line approach to managementReference Balon and Segraves17 but this should be undertaken cautiously and preferably in patients who have successfully completed continuation treatment. ‘Drug holidays’ (with brief interruptions of treatment) have been adopted with some antidepressantsReference Balon and Segraves17 but only a proportion of patients describe improvements in sexual function; depressive symptoms tend to worsen and discontinuation symptoms can be troublesome.

Many compounds have been advocated for relieving sexual dysfunction associated with antidepressant drug treatment, although relatively few have been subject to rigorous evaluation.Reference Williams, Edin, Hogue, Fehnel and Baldwin15 Randomised placebo-controlled trials indicate efficacy for bupropion, buspirone, olanzapine, testosterone gelReference Amiaz, Pope, Mahne, Kelly, Brennan and Kanayama18 and the phosphodiesterase-5 inhibitors sildenafil (in male and female patientsReference Nurnberg, Hensley, Heiman, Croft, Debattista and Paine19) and tadalafil (in male patientsReference Segraves, Lee, Stevenson, Walker, Wang and Dickson20). Although switching from one antidepressant to another seems reasonable and is a commonly adopted practice,Reference Balon and Segraves17 placebo-controlled evidence of efficacy for this approach rests on a study of switching from sertraline to nefazodone (which is no longer widely available).Reference Taylor, Rudkin and Hawton16

Future and current practice

Coming years may see the adoption of laboratory approaches to identifying patient subgroups at increased risk of developing sexual side-effects of antidepressant treatment, through knowledge of genetic polymorphisms or other biological markers. Also, treatment options may be widened through the advent of new treatments with a lower risk of causing sexual problems. For the time being, management rests largely on sensitive enquiries to establish whether sexual difficulties are present; choosing antidepressants with a lower propensity to worsen sexual dysfunction, when other considerations allow; carefully reducing antidepressant dosage, when this is feasible; and in gaining greater familiarity with the potential benefits and drawbacks of adjuvant treatments.


This editorial is based on a talk given during the International Congress of the Royal College of Psychiatrists, Liverpool, 10-13 July 2012.

Declaration of interest

On behalf of his employer, D.S.B. has held research grants from Bristol-Myers Squibb, Cephalon, Eli Lilly, GlaxoSmithKline, H. Lundbeck A/S, Pierre Fabre, Pfizer, Roche, and Vernalis. He has served on advisory boards hosted by AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Grunenthal, H. Lundbeck A/S, Pierre Fabre, and Pfizer.


1 DeRogatis, LR Burnett, AL The epidemiology of sexual dysfunctions. J Sex Med 2008; 5: 289300.Google Scholar
2 Lewis, RW Fugl-Meyer, KS Corona, G Hayes, RD Laumann, EO Moreira, ED et al Definitions/epidemiology/risk factors for sexual dysfunction. J Sex Med 2010; 7: 1598–607.Google Scholar
3 Basson, R Rees, P Wang, R Montejo, AL Incrocci, L Sexual function in chronic illness. J Sex Med 2010; 7: 374–88.Google Scholar
4 Hegeman, JM Kok, RM van der Mast, RC Giltay, EJ Phenomenology of depression in older compared with younger adults: meta-analysis. Br J Psychiatry 2012; 200: 275–81.Google Scholar
5 Williams, K Reynolds, MF. Sexual dysfunction in major depression. CNS Spectr 2006; 11 (suppl 9): 1923.Google Scholar
6 Abler, B Seeringer, A Hartmann, A Grön, G Metzger, C Walter, M et al Neural correlates of antidepressant-related sexual dysfunction: a placebo-controlled fMRI study on healthy males under subchronic paroxetine and bupropion. Neuropsychopharmacology 2011; 36: 1837–47.Google Scholar
7 Frohlich, PF Meston, CM. Evidence that serotonin affects female sexual functioning via peripheral mechanisms. Physiol Behav 2000; 71: 383–93.Google Scholar
8 Serretti, A Chiesa, A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. J Clin Psychopharmacol 2009; 29: 259–66.Google Scholar
9 Gartlehner, H Hansen, RA Morgan, LC Thaler, K Lux, L Van Noord, M et al Comparative benefits and harms of second-generation antidepressants for treating major depressive disorder. An updated meta-analysis. Ann Int Med 2011; 155: 772–85.Google Scholar
10 Watanabe, N Omori, IM Nakagawa, A Cipriani, A Barbui, C Churchill, R et al Mirtazapine versus other antidepressive agents for depression. Cochrane Database Syst Rev 2011; 12: CD006528.Google Scholar
11 Hickie, IB Rogers, NL Novel melatonin-based therapies: potential advances in the treatment of major depression. Lancet 2011; 378: 621–31.Google Scholar
12 Rizvi, SJ Yeung, NW Kennedy, SH Instruments to measure sexual dysfunction in community and psychiatric populations. J Psychosom Res 2011; 70: 99109.Google Scholar
13 Baldwin, D Bridgman, K Buis, C Resolution of sexual dysfunction during double-blind treatment of major depression with reboxetine or paroxetine. J Psychopharmacol 2006; 20: 91–6.Google Scholar
14 Giuliano, F Hellstrom, WJG. The pharmacological treatment of premature ejaculation. Br J Urol Int 2008; 20: 668–75.Google Scholar
15 Williams, VS Edin, HM Hogue, SL Fehnel, SE Baldwin, DS Prevalence and impact of antidepressant-associated sexual dysfunction in three European countries: replication in a cross-sectional patient survey. J Psychopharmacol 2010: 24: 489–96.Google Scholar
16 Taylor, MJ Rudkin, L Hawton, K Strategies for managing antidepressant-induced sexual dysfunction: systematic review of randomised controlled trials. J Affect Disord 2005; 88: 241–54.Google Scholar
17 Balon, R Segraves, RT. Survey of treatment practices for sexual dysfunction(s) associated with anti-depressants. J Sex Marital Ther 2008; 34: 353–65.Google Scholar
18 Amiaz, R Pope, HG Mahne, T Kelly, JF Brennan, BP Kanayama, G et al Testosterone gel replacement improves sexual function in depressed men taking serotonergic antidepressants: a randomized, placebo-controlled clinical trial. J Sex Marital Ther 2011; 37: 243–54.Google Scholar
19 Nurnberg, HG Hensley, PL Heiman, JR Croft, HA Debattista, C Paine, S Sildenafil treatment of women with antidepressant-associated sexual dysfunction. JAMA 2008; 300: 395404.Google Scholar
20 Segraves, RT Lee, J Stevenson, R Walker, DJ Wang, WC Dickson, RA Tadalafil for treatment of erectile dysfunction in men on antidepressants. J Clin Psychopharmacol 2007; 27: 62–6.Google Scholar
Submit a response


No eLetters have been published for this article.