Is there a withdrawal syndrome in adult males when stopping phosphodiesterase (PDE) inhibitors like Viagra (sildenafil) or Cialis (tadalafil) for erectile dysfunction?

No Withdrawal Syndrome from PDE5 Inhibitors

There is no evidence of a withdrawal syndrome when stopping phosphodiesterase-5 (PDE5) inhibitors like Viagra (sildenafil) or Cialis (tadalafil). When these medications are discontinued, erectile dysfunction simply returns to pre-treatment baseline levels without any additional symptoms or rebound worsening 1, 2.

What Happens When PDE5 Inhibitors Are Stopped

• Erectile function returns to baseline within days, not worse than before treatment started 1
• In a randomized withdrawal study, men who stopped sildenafil after 16 weeks of successful treatment experienced a return to pre-treatment erectile dysfunction levels within the 8-week observation period, with no evidence of rebound worsening or withdrawal symptoms 1
• The underlying disease causing ED persists when PDE5 inhibitors are withdrawn, which explains why erectile dysfunction recurs—this is not withdrawal, but rather the re-emergence of the original pathology 2

Key Clinical Evidence

• A high-quality randomized withdrawal trial specifically evaluated what happens when sildenafil is stopped after prolonged use: 200 men with psychogenic or mixed-etiology ED were successfully treated with sildenafil for 16 weeks, then randomized to either continue sildenafil or switch to placebo 1
• Men switched to placebo experienced return of ED to pre-treatment values (P < 0.0001 versus continued sildenafil group), but no symptoms beyond loss of treatment effect were reported 1
• The study explicitly monitored for adverse events during the withdrawal phase and found no withdrawal-related symptoms—only the expected return of erectile dysfunction 1

Why ED Returns (Not Withdrawal)

• PDE5 inhibitors treat symptoms, not the underlying cause of erectile dysfunction 2
• The medications work by enhancing nitric oxide-mediated vasodilation in penile arteries during sexual stimulation, but do not cure the vascular, neurologic, hormonal, or psychological factors causing ED 3
• When treatment stops, the underlying endothelial dysfunction, vascular disease, diabetes-related damage, or other pathology remains unchanged 4, 2

Long-Term Safety Data

• Long-term studies (up to 1 year) show that 90% of patients continue treatment successfully with only 1% discontinuing due to lack of efficacy, indicating no tolerance development or need for dose escalation 1
• Postmarketing surveillance has revealed no new cardiovascular safety concerns and no reports of withdrawal syndromes 3
• The American College of Physicians confirms that PDE5 inhibitors must be continued for improvements to be maintained, but stopping them does not cause harm beyond return of ED 4

Clinical Implications

• Patients can safely stop PDE5 inhibitors at any time without tapering or concern for withdrawal effects 1, 2
• Counsel patients that if they stop treatment, their erectile dysfunction will return to baseline levels within days, which is expected and not a sign of dependence or withdrawal 1
• No special monitoring is needed when discontinuing PDE5 inhibitors 4, 1
• If patients wish to resume treatment after a break, they can restart at their previous effective dose without concern 1