Can propranolol (beta-blocker) cause lethargy?

Propranolol and Lethargy

Yes, propranolol can cause lethargy as a documented side effect. Lethargy is recognized as a central nervous system adverse effect of propranolol in both clinical guidelines and FDA labeling 1, 2.

Mechanism and Presentation

• Propranolol is a non-selective beta-blocker that crosses the blood-brain barrier due to its lipophilic properties, which contributes to its central nervous system effects 2
• Lethargy appears to be dose-related in immediate-release formulations of propranolol 1
• Lethargy may present as part of a constellation of symptoms including fatigue, weakness, and mental depression 1

Evidence from Guidelines and Drug Labeling

• The FDA drug label explicitly lists lethargy as an adverse reaction in the central nervous system category 1
• The European Heart Journal guidelines identify lethargy as one of the most common reported adverse symptoms of beta-blockers, including propranolol 2
• In pediatric patients treated for infantile hemangiomas, lethargy is recognized as a potential manifestation of neuroglycopenia (related to hypoglycemia) that can occur with propranolol therapy 2

Risk Factors and Associated Symptoms

• Lethargy may be more pronounced in:
  • Patients on higher doses of propranolol 1
  • Elderly patients 2
  • Patients with reduced hepatic clearance 2
• Lethargy often occurs alongside other central nervous system effects:
  • Mental depression manifested by insomnia 1
  • Weakness and fatigue 1, 3
  • Vivid dreams 1
  • Decreased performance on neuropsychometric tests 1

Clinical Implications and Management

• If a patient develops significant lethargy on propranolol:
  • Consider dose reduction if the therapeutic effect can be maintained 2
  • Evaluate for hypoglycemia, especially in pediatric patients or those with restricted oral intake 2
  • Consider switching to a less lipophilic beta-blocker that has reduced blood-brain barrier penetration 2
  • Monitor for other central nervous system effects that may accompany lethargy 1

Special Considerations

• In pediatric patients, propranolol-induced lethargy may:

  • Impair school performance 2
  • Be a sign of hypoglycemia when accompanied by poor feeding 2
  • Require close monitoring and potential dose adjustment 2

• In adults with cardiovascular conditions, lethargy may be mistaken for:

  • Worsening of underlying cardiac disease 2
  • Depression or other psychiatric conditions 4

Common Pitfalls

• Failing to recognize lethargy as a medication side effect rather than a new medical condition 4
• Not distinguishing between lethargy due to direct CNS effects versus lethargy as a symptom of propranolol-induced hypoglycemia 2
• Overlooking that lethargy may be part of a broader constellation of central nervous system effects 1
• Not considering that symptoms of fatigue and lethargy may be related to propranolol's effects on inspiratory muscle performance 3