Antidepressant-Induced Sexual Dysfunction Flavio Guzman, MD

Overview Normal sexual response Depression and sexual dysfunction Antidepressant-induced sexual dysfunction Mechanisms involved Agents with lower risk of SD Management strategies

Normal sexual response: 4 phases Resolution Muscular relaxation, well being. Men: refractory period. Orgasm Peak of sexual pleasure, release of sexual tension, contraction of perineal muscles and reproductive organs Excitement Subjective sense of sexual pleasure, physiological changes Desire Fantasies and desire to have sexual activity Baldwin, D., & Mayers, A. (2003). Sexual side-effects of antidepressant and antipsychotic drugs.  Advances in Psychiatric Treatment, 9(3), 202-210.

Sexual dysfunction and depression Resolution Orgasm Excitement Desire Comparative studies indicate higher levels of sexual dysfunction Loss of sexual desire may be more common than disorders of arousal and orgasm Baldwin, D., & Mayers, A. (2003). Sexual side-effects of antidepressant and antipsychotic drugs.  Advances in Psychiatric Treatment, 9(3), 202-210.

Sexual dysfunction and depression The Zurich study: Prospective, cohort study Young people: 591 subjects 28-35 years old Group Non-depressed subjects Depressed patients Treated depressed patients SD prevalence 26% 45% 62% Baldwin, D., & Mayers, A. (2003). Sexual side-effects of antidepressant and antipsychotic drugs.  Advances in Psychiatric Treatment, 9(3), 202-210.

Antidepressants and sexual dysfunction Seen with TCAs, MAOIs, SNRIs, and SSRIs Underestimated incidence: up to 70% of patients treated with SSRIs and SNRIs More common with paroxetine Frequent impairments: orgasm and ejaculatory 70% AD-Induced Sexual Dysfunction Treatment adherence Clayton, A. H., H. A. Croft, and L. Handiwala. "Antidepressants and sexual dysfunction: mechanisms and clinical implications." Postgraduate medicine126.2 (2014): 91-99. Mago, Rajnish, Rajeev Mahajan, and Dileep Borra. "Antidepressant-Induced Sexual Dysfunction: an Updated Review." Current Sexual Health Reports(2014): 1-7.

Antidepressants and sexual dysfunction Spontaneous reporting Direct questioning

Antidepressants associated with lower incidence of SD Bupropion Studies show lower incidence of SD than: Fluoxetine Escitalopram Mirtazapine Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction Lower incidence than SSRIs (24% vs 58%) and SNRIs (24% vs 73%) Nefazodone Montejo et al Lower incidence than SSRIs and SNRIs Clayton, A. H., H. A. Croft, and L. Handiwala. "Antidepressants and sexual dysfunction: mechanisms and clinical implications." Postgraduate medicine126.2 (2014): 91-99. Mago, Rajnish, Rajeev Mahajan, and Dileep Borra. "Antidepressant-Induced Sexual Dysfunction: an Updated Review." Current Sexual Health Reports(2014): 1-7.

Antidepressants associated with lower incidence of SD Vilazodone (unclear) Laughren et al (FDA, 2011):“inconsistent” data from sexual clinical scales Mago et al (2014): may have lower incidence, verification in prospective studies with ADISD as primary outcome measure needed. Agomelatine In healthy volunteers, SD associated with agomelatine use not greater than placebo Clayton, A. H., H. A. Croft, and L. Handiwala. "Antidepressants and sexual dysfunction: mechanisms and clinical implications." Postgraduate medicine126.2 (2014): 91-99. Mago, Rajnish, Rajeev Mahajan, and Dileep Borra. "Antidepressant-Induced Sexual Dysfunction: an Updated Review." Current Sexual Health Reports(2014): 1-7.

Antidepressants and SD: potential mechanisms Norepinephrine Increases sexual arousal Dopamine Motivated behaviors (sexual) Sexual arousal, penile erection DA antagonists can reduce sexual performance Serotonin (5-HT) Can reduce sexual behavior Suspension of vasocongestion Decrease NO function Baldwin, D., & Mayers, A. (2003). Sexual side-effects of antidepressant and antipsychotic drugs.  Advances in Psychiatric Treatment, 9(3), 202-210.

Lowering the dose Wait and watch Switching Adding an antidote Management Lowering the dose Wait and watch Switching Adding an antidote

Dose lowering Not systematically studied Risk of depression relapse (monitor) Most appropriate for patients on high AD doses “Drug holiday” Discontinuation symptoms Patient might discontinue treatment Clayton, A. H., H. A. Croft, and L. Handiwala. "Antidepressants and sexual dysfunction: mechanisms and clinical implications." Postgraduate medicine126.2 (2014): 91-99.

Wait and watch Simplest strategy Spontaneous improvement: Only in 5-10 % of patients Can take 4 to 6 months Clayton, A. H., H. A. Croft, and L. Handiwala. "Antidepressants and sexual dysfunction: mechanisms and clinical implications." Postgraduate medicine126.2 (2014): 91-99. Mago, Rajnish, Rajeev Mahajan, and Dileep Borra. "Antidepressant-Induced Sexual Dysfunction: an Updated Review." Current Sexual Health Reports(2014): 1-7.

Switching to a different antidepressant Switch to an AD with lower incidence of sexual dysfunction: bupropion, mirtazapine, agomelatine and vilazodone Monitor effectiveness and adverse effects of new AD Clayton, A. H., H. A. Croft, and L. Handiwala. "Antidepressants and sexual dysfunction: mechanisms and clinical implications." Postgraduate medicine126.2 (2014): 91-99. Mago, Rajnish, Rajeev Mahajan, and Dileep Borra. "Antidepressant-Induced Sexual Dysfunction: an Updated Review." Current Sexual Health Reports(2014): 1-7.

Adding an antidote Bupropion Men only: 150 mg/day no more effective than placebo 150 mg twice daily: improve in sexual function Men only: PDE inhibitors: sildenafil, tadalafil Taylor MJ, Rudkin L, Bullemor-Day P, Lubin J, Chukwujekwu C, Hawton K. Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database of Systematic Reviews 2013, Issue 5.

Key Points AISD impacts treatment adherence Difference between spontaneous reporting and direct questioning AD with lower risk of SD: bupropion, mirtazapine, nefazodone, agomelatine, vilazodone (?) Management strategies: Dose reduction Wait and watch Switching Adding a second drug