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Sexual dysfunction associated with major depressive disorder and antidepressant treatment (3)

 

Selective serotonin reuptake inhibitors (SSRIs)
= Serotonin has been found to decrease sexual desire and arousal overall.
= Primary central effects of SSRIs are inhibitory, potentially via
----Decreased dopamine release in the mesolimbic system.
----Suppression of spinal ejaculatory centers.
= Vilazodone, a novel SSRI
----Acts on the 5-HT transporter, partial against at both presynaptic and postsynaptic 5HT-1A receptors.
----Suggests that it might have a more favorable profile relative to sexual function.

Antidepressant medications: a review of the evidence for drug-induced sexual dysfunction. J Affect Disord 2002

 

Serotonin and norepinephrine reuptake inhibitors (SNRIs)
= Venlafaxine (Efexor), more potent 5-HT reuptake inhibitor than noradrenergic reuptake inhibitor, especially at low doses.
----Sexual side effects: Venlafaxine > bupropion, agomelatine [J Clin Psychopharmacol 2008]
= Desvenlafaxine, major metabolite of venlafaxine and so exhibits a similar receptor affinity profile.
= Duloxetine, greater affinity for 5-HT and noradrenergic reuptake transporters than venlafaxine, and activates both receptor types in a balanced ratio
----Less effect on sexual function compared with that of an SSRI. [J Sex Med 2007]

 

Tricyclic antidepressants
= Studies on SD related to tricyclic antidepressants are scarce.
= Amitriptyline
----Carries a rate of SD higher than placebo.
----Presumably because of its anticholinergic effect [Cochrane Database Syst Rev 2012]
= Clomipramine
----90% of clomipramine-treated patients report orgasmic dysfunction [Maturitas 2013]

 

Mono-amine oxidase inhibitors
= Studies on MAOI-related SD are scarce
= Moclobemide
----Does not differ from placebo in rates of SD. [J Clin Psychopharmacol 2009]
----Increased sexual desire: Moclobemide> doxepin (tricyclic antidepressant) [Int Clin Psychopharmacol 1993]
----Similar antidepressant efficacy to SSRIs but about 1/10 the rate of SD [Neuropsychopharmacol 2000]
= Transdermal, Selegiline
----No improvement of function at a dose of 6 mg/24h [J Clin Psychiatry 2007]

 

Other antidepressants
= Bupropion, selective dopamine and norepinephrine reuptake inhibitor.
----Effect on central dopamine levels/function.
----Have a more favorable SD profile compared with other antidepressants.
----A lower rate of SD compared with escitalopram, fluoxetine, paroxetine and sertraline. [Ann Intern Med 2011]
----SD risk: citalopram and venlafaxine XR > paroxetine and sertraline > fluoxetine > Bupropion. [J Clin Psychiatry 2002]
= Mirtazapine, noradrenergic and specific serotonergic antidepressant.
----Switched from an SSRI to mirtazapine for up to 6 weeks were less likely to experience reemergence of SD. [J Clin Psychiatry 2000]
----No difference between mirtazapine and placebo in treating TESD. [Psychiatr Res 2002]
----Less likely to induce TESD than SSRIs. [CNS Drug 2010]

 

Management
= Choosing an antidepressant with a low incidence of SD.
= Dose reduction.
= Medication switching or augmentation:
----Bupropion, minimize risk of antidepressant-associated SD.
----Mirtazapine.
----Vilazodone
= Addition of an antidote:
----PDE-5 inhibitors like sildenafil [Viagra](76% effective in treating ED) [Gen Hosp Psychiat 2013], tadalafil, and vardenafil
----Exogenous testosterone supplement
= Waiting for spontaneous remission (adaptation/tolerance):
----Require a long wait, increasing the risk of noncompliance with treatment.
----Few as 5~10% of patients actually experience remission. [J Clin Psychiatry 2006]
= Cognitive therapy:
----Focusing on distorted beliefs, attitudes, and thought patterns, such as all-or-nothing thinking, overgeneralizing, and catastrophizing.
----Psychotherapy and medications appear to exhibit a synergistic effect.
= Lifestyle interventions:
----Improved diet, exercise, smoking cessation, and reduced alcohol intake.

 

Strategies for managing sexual dysfunction in depression

Strategies	pros	cons
Tolerance	Simple	Low success rate
Lower dose	Simple	Relapse
Drug holiday	No additional medication	Potential discontinuation symptoms; Relapse
Substitution	Single agent successful	Fear of  therapeutic failure
Antidotes	Good success rate	Increased side effect; cost

Assessment and management of sexual dysfunction in the context of depression, Pratap Rao Chokka, Jeffrey R. Hankey, Therapeutic advances in psychopharmacology 2018

Assessment and management of sexual dysfunction in the context of depression, Pratap Rao Chokka, Jeffrey R. Hankey, Therapeutic advances in psychopharmacology 2018