Editing Disorders of Ejaculation and Orgasm (section)

====== Selective serotonin reuptake inhibitors (SSRIs) ======
* '''Mechanism of Action: block pre-synaptic axonal reuptake of serotonin''' from the synaptic cleft of central serotonergic neurons by 5-HT transporters, resulting in enhanced 5-HT neurotransmission and stimulation of postsynaptic membrane 5-HT receptors.
* '''Ejaculation delay usually occurs within 5-10 days of starting treatment, but the full therapeutic effect may require 2-3 weeks of treatment''' and usually is sustained during long-term use.
*'''<span style="color:#ff0000">Drugs and Dosages'''
**'''<span style="color:#ff0000">Daily dosing'''
***'''<span style="color:#ff0000">Options: paroxetine, clomipramine, sertraline, fluoxetine, or citalopram.'''
**** '''<span style="color:#ff0000">Paroxetine'''
*****10-40mg daily
*****'''<span style="color:#ff0000">Exerts the strongest ejaculation delay</span>''', increasing IELT approximately 8.8x over baseline
**'''On-demand'''
***'''Options: dapoxetine (not available in Canada) or off-label paroxetine, clomipramine, sertraline, and fluoxetine'''
**** '''On-demand administration''' 3-6 hours before intercourse is modestly efficacious and well tolerated but is '''associated with substantially less ejaculatory delay than daily treatment'''
* '''<span style="color:#ff0000">Adverse effects'''
** Usually minor, start in the first week of treatment, and may gradually disappear within 2-3 weeks.
** '''<span style="color:#ff0000">Includes'''
***'''<span style="color:#ff0000">Fatigue'''
***'''<span style="color:#ff0000">Yawning'''
***'''<span style="color:#ff0000">Mild nausea'''
***'''<span style="color:#ff0000">Diarrhea'''
***'''<span style="color:#ff0000">Perspiration'''
*** '''<span style="color:#ff0000">Hypomania''' 
****'''Can occur infrequently; treatment with SSRIs should be avoided in men with a history of bipolar depression'''
***** '''SSRIs are associated with a small increase in the risk for suicidal ideation or suicide attempts in youth but not adults.'''
****** '''Caution is suggested in prescribing SSRIs to young adolescents with PE age ≤ 18 years, and to males with PE and a comorbid depressive disorder, particularly when associated with suicidal ideation.'''
*** '''<span style="color:#ff0000">Weight gain and increased risk of type 2 diabetes</span>''' associated with long-term SSRI use
***'''<span style="color:#ff0000">Priapism</span>'''; rare potential adverse effect of SSRIs
***'''Upper GI bleeding'''
****Platelet serotonin release has an important role in hemostasis and SSRIs, especially with concurrent use of aspirin and NSAIDs, may be associated with increased risk for upper GI bleeding
*** '''Abnormal semen parameters'''
****In males with normal semen parameters, paroxetine has been reported to induce '''abnormal sperm DNA fragmentation''' in a significant proportion of patients, without a measurable effect on other semen parameters. 
*****Fertility potential of a substantial number of men on paroxetine may be adversely affected by these changes in sperm DNA integrity
* '''Patients should be advised to avoid sudden cessation or rapid dose reduction of daily dosed SSRIs, which may be associated with an SSRI withdrawal syndrome'''