Seeking a methodologically rigorous approach to suspected medication-induced erectile dysfunction in polypharmacy. I am interested in experiences and data-driven strategies that go beyond the usual “switch to bupropion or add a PDE5 inhibitor” playbook. Specifically, how are others attributing causality, phenotyping the dysfunction, and structuring deprescribing or substitution while maintaining control of the primary condition?
Working framework for discussion (open to critique and augmentation):
- Causality assessment: Adaptation of the Naranjo/WHO-UMC approach for sexual adverse events, emphasizing temporal association, dose-response, dechallenge/rechallenge, mechanistic plausibility (e.g., serotonergic vs antiandrogenic vs hemodynamic), and exclusion of disease-related contributors.
- Phenotyping: Differentiation of predominant mechanism-
• Hemodynamic/endothelial: older nonselective beta-blockers, thiazides; contrasting data on nebivolol and ARBs possibly improving erectile parameters via NO/endothelial effects.
• Neurotransmitter-mediated: SSRIs/SNRIs (serotonergic inhibition of sexual function), antipsychotics via D2 blockade and hyperprolactinemia, anticholinergic load (TCAs, first-gen antihistamines).
• Endocrine/androgen: opioids (opioid-induced androgen deficiency), 5-alpha-reductase inhibitors, spironolactone, GnRH analogs.
• Alpha-1 blockers and ejaculatory dysfunction (relevant to sexual satisfaction and perceived ED).
- Measurement strategy: Baseline and follow-up IIEF-5 or full IIEF and/or ASEX; targeted labs (AM total T, SHBG/free T, LH/FSH, prolactin, TSH) when mechanism suggests endocrine involvement; NPT/RigiScan to distinguish psychogenic vs organic; penile Doppler in vascular hypotheses.
- Interventions hierarchy:
• Substitutions within class (e.g., paroxetine → sertraline/vortioxetine; nonselective beta-blocker → nebivolol/ACEI/ARB; thiazide → CCB/ARB as appropriate).
• Augmentation (bupropion; buspirone; low-dose aripiprazole for antipsychotic-induced hyperprolactinemia).
• PDE5 inhibitors tailored to mechanism (daily tadalafil for endothelial support vs on-demand sildenafil), with careful review of nitrate/alpha-blocker interactions.
• Dose timing or formulation changes (IR vs XR; evening dosing), only when pharmacodynamics plausibly decouple peak effect from sexual activity and without compromising primary disease control.
• Endocrine-directed therapy (address hypogonadism; manage hyperprolactinemia) when confirmed.
- Safety and feasibility: Preplanned dechallenge-rechallenge in collaboration with the prescriber; avoidance of “drug holidays” where destabilization risk is significant (e.g., antidepressants, antihypertensives); documentation of washout and observation windows appropriate to half-lives and receptor occupancy.
- Individualization: Pharmacogenomics (e.g., CYP2D6/CYP2C19 effects on SSRI exposure; ABCB1 variants), total anticholinergic burden scales, and comorbidity indexing (diabetes, OSA, CVD).
Questions to the group:
1) Has anyone implemented a standardized dechallenge-rechallenge protocol for suspected medication-induced ED with objective and patient-reported endpoints (e.g., IIEF-5 change plus NPT)? What washout and reassessment intervals proved practical and informative without jeopardizing the primary condition?
2) Antihypertensive-related ED: real-world comparative outcomes after switching from older beta-blockers or thiazides to nebivolol, ACEI/ARB, or DHP-CCB. Magnitude of effect on IIEF-5 and time to improvement?
3) SSRI/SNRI-associated sexual dysfunction: beyond bupropion, which augmentations or switches have provided consistent benefit (vortioxetine, mirtazapine, buspirone, cyproheptadine PRN) and what strategies reduced relapse or serotonin-related adverse effects? Any success with dose timing to lower peak serotonergic impact during anticipated sexual activity?
4) Antipsychotic-induced hyperprolactinemia: experiences with aripiprazole adjunct or switch to partial agonists-what prolactin thresholds and timeframes correlate with erectile recovery?
5) Opioid-induced androgen deficiency: outcomes with opioid rotation, dose reduction, versus testosterone replacement; any experience with adjuncts (e.g., low-dose naltrexone) and their impact on erectile parameters?
6) 5-alpha-reductase inhibitors and spironolactone: observed dose-response and reversibility timelines after discontinuation; biomarkers that predict recovery.
7) Has anyone used anticholinergic burden scoring prospectively to predict or mitigate ED risk in patients on multiple agents with anticholinergic properties?
8) Pharmacogenomic-guided psychotropic selection: has this tangibly reduced sexual adverse events in your cohorts? Particular genotypes you now flag as high risk for ED?
9) For PDE5 nonresponders where a medication cause is suspected, what indicators have predicted response after class substitution or dose/formulation adjustments of the culprit drug?
I would value protocols, case series, or even single-patient n-of-1 data with pre/post metrics, including negative findings. The goal is to refine a replicable, mechanism-informed pathway that clinicians and patients can use to evaluate and manage medication-associated erectile dysfunction while maintaining control of the underlying conditions.