Can memantine (N-methyl-D-aspartate receptor antagonist) cause bradycardia?

Memantine and Bradycardia

Memantine can cause bradycardia as evidenced by FDA drug labeling which specifically lists bradycardia as a potential adverse effect in overdose situations. 1

Evidence for Memantine-Induced Bradycardia

• The FDA drug label for memantine explicitly lists bradycardia among the signs and symptoms accompanying memantine overdosage, along with other cardiovascular effects such as ECG changes 1
• Analysis of the French PharmacoVigilance Database found that bradycardia accounted for 7% of serious adverse drug reactions associated with memantine use 2
• A dedicated study of the French PharmacoVigilance Database identified 18 reports of bradycardia associated with memantine, with 7 cases occurring with memantine as the sole suspected drug, and all but one resolving after memantine discontinuation 3
• Experimental studies in halothane-anesthetized dogs demonstrated that memantine can suppress intra-atrial conduction and inhibit intra-ventricular conduction, indicating potential to induce severe bradycardic events through advanced cardiac conduction block in susceptible patients 4

Mechanism of Bradycardia

• While memantine is an NMDA receptor antagonist, its cardiovascular properties appear to be complex and not fully understood 3
• Unlike acetylcholinesterase inhibitors (AChEIs) which cause bradycardia through increased vagal tone, memantine's mechanism for inducing bradycardia remains unclear 5, 3
• Animal studies suggest memantine may affect cardiac conduction pathways directly, potentially leading to bradycardia through suppression of intra-atrial conduction and inhibition of intra-ventricular conduction 4

Risk Factors and Clinical Considerations

• Bradycardia risk may be higher in:

  • Elderly patients 2
  • Patients with underlying cardiac disease 5
  • Patients taking other medications that can affect heart rate (beta-blockers, calcium channel blockers, digoxin) 5
  • Overdose situations 1

• Physicians should take special care when prescribing memantine to patients who are already on medications known to cause bradycardia 2

Management of Memantine-Induced Bradycardia

• For symptomatic bradycardia that is unresponsive to medication discontinuation, consider:
  • Discontinuation of memantine as the first step, as most cases resolve after discontinuation 3
  • For persistent hemodynamically unstable bradycardia, temporary transvenous pacing may be reasonable 6
  • Atropine may be considered for bradycardia causing hemodynamic instability 6

Comparison with Other Alzheimer's Disease Medications

• Acetylcholinesterase inhibitors (AChEIs) like donepezil, rivastigmine, and galantamine are more commonly associated with bradycardia than memantine 6
• The U.S. Preventive Services Task Force notes that bradycardia and related adverse effects (falls, syncope) may result from taking AChEIs, while memantine did not differ from placebo in the percentage of withdrawals due to adverse effects in trials 6
• However, comparative studies show that bradycardia still occurs with memantine (7% of adverse reactions) compared to donepezil (10% of adverse reactions) 2

Monitoring Recommendations

• Monitor vital signs, particularly heart rate, when administering memantine, especially in elderly patients or those with cardiac comorbidities 5
• Be vigilant for signs of bradycardia when memantine is combined with other medications that can affect heart rate 5, 2
• In overdose situations, be alert for bradycardia along with other symptoms such as confusion, coma, ECG changes, and increased blood pressure 1