SSRIs and Sexual Dysfunction

1. SSRIs and Sexual Dysfunction Beyond the medical school teaching: “Wellbutrin/Bupropion is Better ” Farah Ahmad, MPH Sexual Health Scholars Program 2011

2. Goals of Presentation • Be able to list common medications (non-psychotropic) and common medical conditions that have been associated with sexual dysfunction. • Describe the prevalence of SSRI-induced sexual dysfunction, what types of sexual dysfunctions are most common, and if there are any gender-differences studied in the literature. • Be able to state treatment strategies to address sexual dysfunction (those found in case studies as well as RCTs) • Know 3 research needs/areas for future research on this topic

3. But I’m not interested in Psychiatry…Do you mind if I sleep through this presentation?

5. Substance Abuse and Mental Health Services Administration. (2009). Results from the 2008 National Survey on Drug Use and Health: National Findings (Office of Applied Studies, NSDUH Series H-36, HHS Publication No. SMA 09-4434). Rockville, MD.

6. Sexual dysfunction sucks. Sucks so much that it’s understandable that some people stop taking the medication that may be causing these side effects. Even knowing it may mean a return to despair, struggling to function, emotional pain, loss of concentration, etc.

7. Indirect Costs of Depression Children of depressed parents have higher rates for affective disorders and are especially at risk for MDD ( 6 x higher than control groups). Downey, G. & Coyne, J.C., (1990). Children of depressed parents: an integrative review. Psychological Bulletin, 108(1): 50-76 According to Weissman et al, a mother whose depression goes into remission can result in the child remitting their diagnosis, the child remaining free of psych diagnoses after 3 months, and reduced symptoms and diagnoses in the child (compared to children of still depressed mothers) Weissman, M.M., et al, (2006). Remissions in maternal depression and child psychopathology. A Star*D-Child report. Journal of the American Medical Association, 295 (12), 1389-1398

8. And now for a brief math lesson…. Baseline rates of sexual dysfunction + depression-related sexual dysfunction + SSRI-associated sexual dysfunction = And oh yeah….these are all REALLY hard topics to talk about with medical providers!!! So what can we do???

9. But I asked him if he had any side effects to the medication and he said no!!! Have you had any side effects? Nope! Except…with the ladies…!!! Great!

10. Ask about sexual dysfunction! Don’t wait for patients to report! Reported rates of sexual dysfunction due to SSRIs are most likely underestimates. • Montejo-Gonzales et al. found that rates of sexual dysfunction due to SSRIs were reported to physicians at 14% spontaneously but 58%when physicians asked direct questions. • Among patients treated with citalopram or paroxetine, Landen et al. found fewer patients (6%) reported SD spontaneously versus 41%who reported it when directly questioned about it. As cited in Haberfellner. A review of the assessment of anti-depressant-induced sexual dysfunction used in randomized, controlled trials. Pharmopsychiatry 2007; 40: 173-182.

11. Baseline sexual dysfunction assessment • Pretreatment and if possible premorbid sexual functioning • Comorbid psychiatric disorders and substance abuse (including smoking hx) • Medications including over the counter drugs • Sexual functioning during period of depression but prior to starting antidepressants • Interpersonal problems in relationship • Other stressors

13. Medical Conditions Associated with SD Adrenal disease Alcoholism Atherosclerosis Cardiac disease Central nervous system disease Diabetes Liver disease Peripheral nervous system disease Pituitary disease Thyroid disease Physical Trauma **Don’t forget about mental health causes! (including sexual violence)

14. And a few more for people with a uterus…! Pelvic surgery or Trauma Hormonal= menopause, postpartum hormonal deficiency Endometriosis Fibroids Vaginal Infection Pelvic Floor disorders Interstitial Cystitis UTI Urinary tract infections can affect anyone but are more common in the shorter urethra of women.

15. What else is going on in their lives? Death in family Tornado? Work Fight with partner Bills Sick Child Upcoming Move No sleep School Chronic illness Caretaker for parent Life!

16. Do you have sexual dysfunction now? How about now? Now? Do you have sexual dysfunction now? How about now? Now? Do you have sexual dysfunction now? How about now? Now? Do you have sexual dysfunction now? How about now? Now? Do you have sexual dysfunction now? How about now? Now? Do you have sexual dysfunction now? How about now? Now? Do you have sexual dysfunction now? How about now? Now? Do you have sexual dysfunction now? How about now? Now? Once is not enough! Keep asking!(But maybe not as many times as listed above!)

17. Doc…what do you mean by ‘sexual dysfunction’ The types of sexual dysfunction related to antidepressants can include: 1. Altered sexual desire, including loss or lack of desire 2. Orgasmic and ejaculatory dysfunction, including anorgasmia, hyperorgasmia, painful orgasm and inhibited ejaculation 3. Erectile problems, including erectile dysfunction (impotence), priapism and painful erection 4. Other problems, including problems of sexual arousal, reduced sexual satisfaction, lubrication, dyspareunia and vaginismus Rudkin L, Taylor MJ, Hawton KKE. Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD003382. DOI: 10.1002/14651858.CD003382.pub2.

18. Masters and Johnson’s Model Go, M & J!!!!!!! Uhh…I don’t think that’s what they meant by Excitement…

19. Rates of Sexual Dysfunction among Participants without global sexual dysfunction (n=3114) Only 6.5% were free of sexual dysfunction. 96% of women and 98% of men had impairment in at least one phase of sexual functioning 80% had dysfunction in more than one phase Dysfunction in orgasmic phase: 56.6% Dysfunction in Arousal/Excitement Phase: 80% Clayton, A., Keller, A., and McGarvey, E.L. (2005). Burden of phase-specific sexual dysfunction with SSRIs. Journal of Affective Disorders, 91, (27-32). Dysfunction in Desire Phase (82.4%)

20. Men w/ no sexual dysfunction 2.9% Women w/ no sexual dysfunction: 7.8% Phase-specific Rates of SD 85.1% 45.4% 71.0% 83.3% 91.2% 79%

21. Prevalence of SD by Anti-depressant in Two Large Studies n= 6297 n= 1022

22. Possible Management Strategies Yohimbine-α2-adrenergic receptor antagonist Nefazodone, Cryptoheptadine, granisetron-Serotonin 5-HT2 receptor antagonist Mirtazapine- α2-adrenergic receptor antagonist and Serotonin 5-HT2 and 5-HT3receptor antagonist Dextroamphetamine and Methylphenidate- psychostimulants Bupropion- dopaminergic/noradrenergic agent Gingko Biloba- herb Sildenafil – phosphodiesterase inhibitor Buspirone- 5-HT2 1A- agonist Dose Reduction/Switching Concomitant medications Psychotherapeutic Approaches Fava M., and Rankin, M.,(2002). Sexual Functioning and SSRIs. Journal of Clinical Psychiatry; 63 (suppl 5): 13-16 Rudkin L, Taylor MJ, Hawton KKE. Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD003382. DOI: 10.1002/14651858.CD003382.pub2.

23. What do RCTs tell us? • A Cochrane study reviewed randomized controlled trials (and 3 subgroup analysis of a larger RCT) that assessed management strategies for antidepressant induced sexual dysfunction • 15 trials involved 904 people • 14 trials involved continuing SSRI medication but adding an additional medication. One trial included switching from SSRI to nefazodone. • All included studies reported blinding for subjects and assessors

24. Bupropion vs. Placebo The Challenge: Does augmenting SSRI treatment with Bupropion increase sexual function and/or satisfaction more than a placebo?

25. Mirtazapine vs. Placebo

26. Buspirone vs. Placebo The Challenge: Does augmenting SSRI treatment with Buspirone increase sexual function and/or satisfaction more than a placebo?

27. Nefazodone vs. Sertraline The Challenge: What better treats sertraline-associated sexual dysfunction? Switching to Nefazodone… or restarting Sertraline after a 2 week “washout period” where dysfunction resolved

28. Sildenafil vs. Placebo The Challenge: Does augmenting SSRI treatment with Viagra increase sexual function and/or satisfaction more than a placebo?

29. Viagra for women!??! Whaaaaaaaaaat?

30. No such luck….Augmenting with the following were not statistically better than placebo in the Cochrane RCTs • Mirtazapine vs placebo in females • Yohimbine vs placebo in females • Amantidine augmentation in females • Gingko biloba vs placebo • Ephedrine vs placebo • Buspirone vs placebo

31. So what have we learned….? …Besides that I have an obsession with clipart?

32. Remember: SIGNIFICANT results in research may not always be CLINICALLY SIGNIFICANT

33. Methodological Problems in Research Studies Not randomized Not Blinded or Double Blinded study No Placebo Group or comparison group No baseline assessment of sexual function/dysfunction Using self-report to assess SD rather than validated measure Confounders- other comorbidities (chronic illness, depression, anxiety) or use of medications that can cause SD) Small study (wide confidence intervals)

34. Comparability of Studies Studies differ on characteristics such as: Gender How long participant has to be “depression-free” Length of time of the study Dosage of medication administered Inclusion/Exclusion Criteria Controlled Variables How to measure “sexual dysfunction” Whois measuring the dysfunction? (Participant or Clinician?) You say Potato… …I say Turnip

35. ASEX SSES IIEF… HUH? Arizona Sexual Experiences Scale (ASEX) Sexual Side Effects Scale (SSES) International Index of Erectile Function (IIEF) Brief Index of Sexual Functioning for Women (BISF-W) Erective Dysfunction Inventory of Treatment Satisfaction (EDITS) Feigher Sexual Function and Satisfaction Questionnaire Udvalg fur Kliniske Undersogelser side effect rating scale Massachusetts General Hospital Sexual Functioning Questionnaire Clinical Global Impression Scale, adapted for Sexual Function (CGI-SF) Sexual Encounter Profile diaries Visual analogue scales Changes in Sexual Functioning Questionnaire (CSFQ) questionnaire developed by investigator

36. Areas for More Research Pediatric population- Children and adolescents are often prescribed SSRIs. Over an 11 year period, only eight MedWatch reports were filed of SSRI-induced sexual dysfunction in adolescents. Only one “letter to the editor” anecdotally reported 3 of 5 adolescents on SSRIs who had SD. In a review of 31 pediatric clinical trials, only ONE person out of 1,346 total participants was reported to have citalopram-induced SD. Good news??? Or not enough research!? Scharko, A.M. (2004). Selective Serotonin Reuptake Inhibitor-Induced Sexual Dysfunction in Adolescents: A Review. J . AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 43:9, 1071-1079

37. What happens over time? Case: 29 year old man who reported normal sexual functioning. Prescribed fluoxetine at age 18 which he took for a total of 4 months. A few days after starting medication, he noticed that he no longer had nocturnal or morning erections, required a great deal of stimulation for erection and ejaculation. His libido was unaffected. Even after 11 years, SD has not resolved and imaging studies (Doppler ultrasound shows good blood flow, cavernosal study shows no leakage in veins). Neurology testing indicates no problems related to spine. Csoka A, Bahrick A, and Mehtonen O-P. Persistent sexual dysfunction after discontinuation of selective serotonin reuptake inhibitors. J Sex Med 2008;5:227–233.

38. The patient mentioned in the previous slide had not been informed of possible sexual side effects…let alone the possibility of permanent dysfunction Exercise: How would you counsel someone on the sexual side effects of medication….without making them sound so scary that none of your patients want to address their depression?!

39. Add ‘Informed Consent’ to the Baseline Assessment!!!

40. Goals of Presentation • Be able to list common medications (non-psychotropic) and common medical conditions that have been associated with sexual dysfunction. • Describe the prevalence of SSRI-induced sexual dysfunction, what types of sexual dysfunctions are most common, and if there are any gender-differences studied in the literature. • Be able to state treatment strategies to address sexual dysfunction (those found in case studies as well as RCTs) • Know 3 research needs/areas for future research on this topic