Does clonidine cause bradycardia (abnormally slow heart rate)?

From the Guidelines

Yes, clonidine can cause bradycardia (abnormally slow heart rate). Clonidine is a centrally-acting alpha-2 adrenergic agonist commonly used to treat hypertension, ADHD, anxiety disorders, and to manage withdrawal symptoms. When clonidine stimulates alpha-2 receptors in the brain stem, it reduces sympathetic outflow from the central nervous system, leading to decreased heart rate, blood pressure, and peripheral vascular resistance.

Key Points to Consider

• Bradycardia typically occurs at therapeutic doses and is more common during initial treatment or after dose increases.
• The risk is higher in patients with pre-existing cardiac conduction disorders, those taking other medications that slow heart rate (like beta-blockers or certain calcium channel blockers), and in elderly patients.
• Patients starting clonidine should be monitored for symptoms of bradycardia such as dizziness, fatigue, or syncope.
• The bradycardia is usually dose-dependent, so dose reduction may help manage this side effect if it becomes problematic.
• Abrupt discontinuation of clonidine should be avoided as it can cause rebound hypertension and tachycardia, as noted in the 2018 guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1.

Management and Monitoring

• Clonidine's effects on heart rate and blood pressure should be closely monitored, especially in vulnerable populations.
• The medication should be tapered off rather than suddenly discontinued to avoid rebound effects, as recommended in the clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents 1.
• Clinicians should be aware of the potential for clonidine to cause bradycardia and take steps to mitigate this risk, including careful dose adjustment and monitoring of patients for signs of bradycardia.

From the FDA Drug Label

The sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular (AV) block, especially in patients taking other sympatholytic drugs There are post-marketing reports of patients with conduction abnormalities and/or taking other sympatholytic drugs who developed severe bradycardia requiring IV atropine, IV isoproterenol and temporary cardiac pacing while taking clonidine. Slowing of the pulse rate has been observed in most patients given clonidine, but the drug does not alter normal hemodynamic response to exercise. Monitor heart rate in patients receiving clonidine concomitantly with agents known to affect sinus node function or AV nodal conduction, e.g., digitalis, calcium channel blockers, and beta-blockers. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concomitantly with diltiazem or verapamil.

Clonidine can cause bradycardia, as evidenced by slowing of the pulse rate in most patients and reports of severe bradycardia in some cases, especially when used with other sympatholytic drugs 2, 2.

• Key factors that increase the risk of bradycardia include:
  • Concomitant use of other sympatholytic drugs
  • Pre-existing sinus node dysfunction or atrioventricular (AV) block
  • Use of agents that affect sinus node function or AV nodal conduction, such as digitalis, calcium channel blockers, and beta-blockers.

From the Research

Clonidine and Bradycardia

• Clonidine, an alpha-adrenergic agent, has been associated with bradycardia in several studies 3, 4, 5.
• The incidence of clonidine-induced bradycardia is low, less than 0.3% 3.
• Certain populations are at risk for severe bradycardia during oral clonidine therapy, including patients with renal insufficiency, clinical sinus node dysfunction, and those taking other sympatholytic agents 3.
• Clonidine's effects on heart rate are mediated through both the heart and the peripheral vascular system, with a decrease in heart rate and stroke volume appearing early in treatment 5.
• The drug reduces cardiac workload and is beneficial in patients with coronary artery disease, with a coronary vasodilating effect 5.
• Clonidine increases cardiac vagal tone, which can reduce the delay between rising systolic blood pressure and baroreflex bradycardia 6.
• Clonidine diminishes GABAergic neurotransmission to cardiac vagal neurons, increasing parasympathetic activity to the heart and decreasing heart rate and blood pressure 7.

Mechanisms and Risk Factors

• Clonidine's mechanisms for inducing bradycardia involve its effects on the central nervous system, including the reduction of sympathetic tone and the increase of parasympathetic activity 4, 7.
• Risk factors for clonidine-induced bradycardia include renal insufficiency, clinical sinus node dysfunction, and concomitant use of other sympatholytic agents 3.
• Clonidine should be used with caution in patients with AV conduction disease, as it can exacerbate existing conduction abnormalities 5.

Clinical Implications

• Awareness of the variable presentation and response of clonidine-induced bradycardia to medical therapy is essential for patient management 3.
• Asymptomatic patients may require only dose reduction or discontinuation of clonidine therapy, while symptomatic patients may respond to intravenous atropine sulfate or isoproterenol therapy 3.
• Temporary artificial pacing may be necessary in severe cases of clonidine-induced bradycardia 3.