What are the next steps for a patient with a history of erectile dysfunction who has failed to respond to Viagra (sildenafil)?

Management of Erectile Dysfunction After Sildenafil Failure

Before abandoning sildenafil, first verify the patient received an adequate trial: at least 5 separate attempts at the maximum 100mg dose with proper timing, adequate sexual stimulation, and counseling on expectations. 1

Step 1: Evaluate for Modifiable Factors Causing PDE5 Inhibitor Failure

Many apparent "failures" are actually inadequate trials that can be salvaged with re-education:

• Check testosterone levels (morning total testosterone) in all PDE5 inhibitor non-responders, as hypogonadism reduces response to sildenafil and testosterone replacement combined with PDE5 inhibitors restores effectiveness in hypogonadal men 2, 3
• Review medication list for drugs causing ED (antidepressants, antihypertensives, antipsychotics account for ~25% of ED cases) 4
• Assess timing and technique: sildenafil requires adequate sexual stimulation and proper timing (taken 30-60 minutes before activity on empty stomach for optimal absorption) 1, 3
• Evaluate relationship factors and partner sexual function, as psychosexual issues reduce treatment success 1
• Screen for heavy alcohol use, which impairs PDE5 inhibitor efficacy 1
• Address cardiovascular risk factors (smoking, obesity, hypertension, diabetes, hyperlipidemia) as these worsen ED and reduce treatment response 2

Step 2: Consider Alternative PDE5 Inhibitor

If sildenafil at maximum dose (100mg) fails after adequate trial, try a different PDE5 inhibitor such as tadalafil (Cialis) 20mg or vardenafil, as some patients respond to one agent but not another despite similar mechanisms 1, 3

• Tadalafil offers longer duration (up to 36 hours) which may benefit patients who prefer spontaneity 3
• Selection depends on patient preference regarding onset time and duration of action 3

Step 3: Second-Line Therapies

After failure of two different PDE5 inhibitors at maximum doses, proceed to more invasive second-line options:

Intracavernous Injection Therapy (Most Effective)

• Alprostadil (PGE1), papaverine, or phentolamine injections are the most effective non-surgical treatment with 66% efficacy in patients self-injecting at home and mean IIEF-EF improvement of 3.21 points versus placebo 1, 3
• Highest potential for priapism among ED treatments, requiring proper patient education 1
• First dose must be administered under healthcare supervision 1

Intraurethral Alprostadil Suppositories

• Less invasive alternative for needle-phobic patients, though less effective than intracavernous injection 1, 3
• First dose requires healthcare supervision due to 3% risk of syncope from hypotension 1
• Combination with penile constriction device increases efficacy over alprostadil alone 1

Vacuum Erection Devices

• 90% initial efficacy, though drops to 50-64% at 2 years 3
• Particularly valuable in older patients with infrequent intercourse 3
• Non-invasive, no systemic side effects 1

Step 4: Third-Line Surgical Option

Penile prosthesis implantation is reserved for end-stage ED after failure of all medical therapies, with high technical success rates and 80% patient satisfaction 3, 5

Critical Safety Considerations

• Absolutely contraindicated: Never use PDE5 inhibitors with nitrates (must wait 24 hours after sildenafil, 48 hours after tadalafil before nitrate administration) due to life-threatening hypotension risk 1, 3, 6
• Cardiovascular assessment: ED is a marker for underlying cardiovascular disease even without cardiac symptoms; all patients require cardiovascular risk stratification 2, 7
• Urgent ophthalmology referral for sudden vision loss (NAION risk) or sudden hearing loss while on PDE5 inhibitors 6

Common Pitfalls to Avoid

• Don't declare treatment failure prematurely: Many "non-responders" simply need dose titration to maximum, proper education on timing/stimulation requirements, or testosterone optimization 1
• Don't ignore testosterone deficiency: The combination of ED with loss of libido makes hypogonadism highly likely and treatable 2
• Don't treat ED in isolation when depression is present: Address underlying psychiatric conditions, though note antidepressants themselves worsen sexual function 2
• Don't assume psychogenic ED requires only counseling: PDE5 inhibitors work for both psychogenic and organic ED and should be initiated concurrently with psychological therapy 2