mechanism of ssri leading to sexual dysfunction

1. How Do SSRIs Cause
Sexual Dysfunction?
Prepared by
Larry Lee Lian Seng

2. INTRODUCTION
• Selective Serotonin Reuptake Inhibitors (SSRIs) are frequently prescribed and are better tolerated than
older antidepressants, but side effects such as sexual dysfunction limit patient acceptance of these
medications.1
• These dysfunctions are categorized by impairment of various sexual response phase.
• Sexual dysfunction is often impaired in MDD due to diminished ability to experience pleasure.
1. Olfson M, Marcus SC. National patterns in antidepressant medication treatment. Arch Gen Psychiatry. 2009;66(8): 848-856.
PHASE DESCRIPTION
Desire Inhibited or hypoactive sexual desire
Arousal
-Male
-Female
Erectile dysfunction
Inadequate lubrication and/or diminished/absent of physiological changes
associated with sexual excitement (e.g. swelling of genitalia)
Orgasm Premature, delayed, or absent orgasm
Pain Painful intercourse, vaginisimus (painful spasmodic contraction of the vagina in
response to physical contact or pressure )

3. POSSIBLE CAUSES OF SEXUAL DYSFUNCTION
• Medical conditions:
• Vascular disease, endocrine disorders, neurological conditions.
• Psychological/psychiatric factors:
• History of sexual trauma, stress, relationship factors, psychiatric disorders
such as depression, substance abuse
• Medications:
• Antihypertensive (Beta-blockers, CCBs)
• Sedatives (alprazolam)
• Anticonvulsants (phenytoin, carbamazepine)
• Neuroleptics (chlorpromazine, clozapine)
• Antidepressants (SSRIs, TCA, MAOIs)
Sajith SG, Morgan C, Clarke D. Pharmacological management of inappropriate sexual behaviours: a review of its evidence, rationale and scope in relation to men with
intellectual disabilities. J Intellect Disabil Res. 2008;52(12):1078-1090.

4. NOT JUST SEROTONIN
• Although SSRIs are relatively selective for the serotonergic system, they affect other
neurotransmitter systems as well.
• Probable role of neurotransmitters and hormones in normal sexual functioning
SSRI Neurotransmitters
Escitalopram (Lexapro) 5-HT
Fluoxetine (Prozac) 5-HT, NE, DA
Fluvoxamine (Luvox) 5-HT
Sertraline (Zoloft) 5-HT, NE, DA
1. Segraves RT. Effects psychotropic drugs on human erection and ejaculation. Arch Gen Psychiatry. 1989; 46(3): 275-284
Phase Physiology
Desire / libido ↑ Dopamine, testosterone, estrogen
↓ Prolaction
Arousal ↑ acetylcholine, dopamine, nitric oxide
Orgasm ↑ Norepnephrine
↓ serotonin

6. HYPOTHESIZED MECHANISM OF SSRI-RELATED SD
• Serotonin reuptake blockade may reduce dopamine activity.
• SSRIs may increase prolactin levels.
• SSRIs may interfere with spinal reflex centers involved in
ejaculation and orgasm.

7. THE ROLE OF NITRIC OXIDE SYNTHASE
• Nitric oxide plays an important role in mediating the penile vasculature changes
essential for erection.
• It promotes penile smooth muscle relaxation via cyclic guanosine monophosphate,
thereby contributing to physiologic erection.1
• SSRIs may inhibit nitric oxide synthase, which reduces nitric oxide levels.
1.Stahl SM. How psychiatrists can build new therapies for impotence. J Clin Psychiatry. 199;59(2):47-48

8. SSRIs COMPARED
• Sexual dysfunction
• Analysis of the clinical trials suggests that fluvoxamine and fluoxetine are less
less likely to produce sexual side effects than paroxetine and sertraline.
• Citalopram has been associated with loss of libido and may be associated
with a relatively higher level of sexual dysfunction compared with sertraline.
• The SSRIs are reported to cause sexual dysfunction in the following
descending order of frequency:
Citalopram (72.7%) > Paroxetine (70.7%) > Sertraline (62.9%) > Fluvoxamine
(62.3%) > Fluoxetine (57.7%).1
1. Montejo AL, Llorca G, Izquierdo JA, Rico-Villademoros F. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter
study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. J Clin Psychiatry. 2001;62 Suppl 3:10-21. PubMed

9. DELAYED EJACULATION
• Increased serotonergic tone acting as an inhibitor at the
hypothalamus level > delayed ejaculation.
• In contrast, noradrenergic tone enhances ejaculation.
• Antidepressants that increase noradrenaline levels and serotonin
levels (SNRI)* induce milder ejaculatory delay.
• Other medications may contribute to sexual dysfunction experienced
by a patient receiving an SSRI.
*Examples of drugs: Venlafaxine, Duloxetine, Desvenlafaxine

10. SSRIs FOR PREMATURE EJACULATION?
• Premature ejaculation occurs when a man ejaculates sooner during sexual intercourse
than he or his partner would like.
• Criteria:
• Always or nearly always ejaculate within one minute of penetration
• Are unable to delay ejaculation during intercourse all or nearly all of the time
• Feel distressed and frustrated, and tend to avoid sexual intimacy as a result
• The use of SSRIs (Paroxetine and Sertraline) in premature ejaculation is OFF-LABEL.
• Some medications used to treat premature ejaculation
• Antidepressant (Fluoxetine, Sertraline)
• Tramadol (if antidepressant fails)
• Phosphodiesterase-5 inhibitor (sildenafil - Viagra, tadalafil - Cialis, vardenafil -

11. CONCLUSION

12. CONCLUSION
• SSRIs can adversely affect all aspects of the human sexual response cycle.
• SSRIs have the highest incidence of treatment-emergent SD.
• Obtaining a detailed sexual history in a culturally sensitive manner may
facilitate early detection and accurate estimate of SSRIs-related sexual
dysfunction and can prompt interventions to enhance patient’s
medication compliance and improve their overall prognosis.

13. Rates of Sexual Dysfunction
Montejo et al, 2011
• N = 1022
• Effexor (159.5)
• Zoloft (90.4)
• Luvox (115.7)
• Prozac (24.5)
• Remeron (37.7)
• 67.3%
• 62.9%
• 62.3%
• 57.7%
• 24.4%

14. Cost of antidepressants (updated as at 30.4.16)
Cost per box Cost per tablet Cost per month (Estimated 1 tab per day)
Mirtazapine 30mg RM 134 RM 4.5 RM 135
Mirtazapine 15mg RM 70 RM 2.3 RM 69
Duloxetine 60mg & 30mg RM 116 RM 4.2 RM 126
Desvenlafaxine 150mg RM 117 RM 4.2 RM 126
Desvenlafaxine 50mg RM 109.72 RM 3.92 RM 117.6
Venlafaxine 75mg RM 113 RM 4 RM 120
Agomelatine 25mg RM 111 RM 3.9 RM 117
Sertraline 50mg RM 26 RM 0.85 RM 25.5
Fluvoxamine 100mg RM 24 RM 0.80 RM 24
Fluvoxamine 50mg RM 24.72 RM 0.41 RM 12.36
Dothiepine 25mg RM 250 RM 0.83 RM 25
Fluoxetine 20mg RM 15 RM 0.50 RM 15
Escitalopram 10mg RM 8 RM 0.26 RM 7.8

15. Thank you!