What are the alternative treatment options for low libido and psychogenic ED in a patient intolerant to bupropion and with ineffective PDE5 inhibitors?

Management of Low Libido and Psychogenic Erectile Dysfunction

For a patient with low libido and psychogenic erectile dysfunction who cannot tolerate bupropion SR 150mg, the most effective approach is to try a lower dose of bupropion at 75mg for several months with gradual titration as tolerated, while considering alternative second-line treatments such as intracavernosal injections if PDE5 inhibitors are ineffective during sleepless nights.

Medication Optimization Strategy

Bupropion Dosing

• Continue bupropion at 75mg for several months as this may help with libido while minimizing side effects of irritability, anger, sweating, thirst, and constipation
• Consider slow titration to 100mg after stabilization at 75mg if tolerated
• Bupropion has shown significant efficacy for treating sexual dysfunction:
  • 46% response rate in women and 75% in men 1
  • Most improvement (>50%) occurs within first 2 weeks and at lower doses (100-200 mg/day) 1
  • Lower doses (150mg vs 300mg) have shown better improvement in sexual desire 2

PDE5 Inhibitor Optimization

• Ensure proper use of PDE5 inhibitors by:
  • Taking on an empty stomach (not after large meals)
  • Ensuring adequate sexual stimulation is present
  • Trying at least 5 separate occasions at maximum dose before declaring ineffective 3
  • Trying a different PDE5 inhibitor if one fails 3, 4
• For sleep-related ED issues when PDE5 inhibitors are ineffective:
  • Consider timing PDE5 inhibitor administration based on anticipated sexual activity
  • Try a longer-acting agent like tadalafil which provides a broader window of opportunity 5

Hormone Management

Testosterone Optimization

• Given previous experience with enclomiphene (which initially improved libido but then led to increased estradiol and decreased testosterone):
  • Consider adjusting enclomiphene dosing or frequency
  • Monitor T/E2 ratio closely
  • Combination therapy with testosterone plus PDE5 inhibitor may be more effective than PDE5 inhibitor alone when testosterone deficiency is present 4

Second-Line Treatments

If optimizing bupropion and PDE5 inhibitors fails:

Intracavernosal Injections

• Intracavernosal injections of alprostadil are highly effective second-line options 3, 4
• Initial trial dose should be administered under healthcare provider supervision 3
• Most effective non-surgical treatment for ED 3

Intraurethral Suppositories

• Alprostadil suppositories are less invasive than injections 3
• First dose should be administered under supervision due to risk of syncope 3, 4

Vacuum Constriction Devices

• Non-pharmacological option with high efficacy rates 4
• Can be used in combination with other treatments

Risk Factor Modification

• Ensure adequate sleep hygiene as sleep disturbances appear to be affecting ED medication efficacy
• Address any cardiovascular risk factors (already on fenofibrate 160mg for high triglycerides)
• Encourage physical activity and weight management (noted patient is not overweight or obese)

Monitoring and Follow-up

• Monitor efficacy, side effects, and any significant changes in health status
• Follow testosterone and estradiol levels if continuing hormonal therapy
• Reassess medication regimen periodically, especially if symptoms change

Cautions and Contraindications

• Avoid nitrates with PDE5 inhibitors due to risk of severe hypotension 3, 4
• Start with lowest possible dose of PDE5 inhibitors when used with interacting medications 4
• Monitor for hypotension, visual changes, and prolonged erection with PDE5 inhibitors 4

This approach prioritizes treating the underlying causes of low libido and ED while minimizing medication side effects, with clear escalation pathways if initial treatments are ineffective.