What is the role of benzodiazepines (BZDs), such as alprazolam (Xanax) or clonazepam (Klonopin), in treating anxiety with palpitations?

Treatment of Anxiety with Palpitations Using Benzodiazepines

Benzodiazepines are FDA-approved and effective for treating panic disorder with palpitations, but should be limited to short-term use (ideally ≤4 weeks maximum) due to risks of tolerance, dependence, and withdrawal. 1, 2

Primary Indication and Evidence Base

• Clonazepam is specifically FDA-approved for panic disorder characterized by palpitations, pounding heart, or accelerated heart rate as one of the core symptoms. 1
• Clinical trials demonstrate that clonazepam 1 mg/day reduces panic attacks by approximately 1 attack per week compared to placebo, with 74% of patients becoming panic-attack-free versus 56% on placebo. 1
• Alprazolam has also shown efficacy in panic disorder with similar outcomes (62% panic-free versus 37% on placebo), though it is not recommended for long-term use in some regions. 1, 2

Recommended Benzodiazepine Selection

For anxiety with palpitations, clonazepam is the preferred agent due to its longer half-life (30-40 hours), which provides sustained anxiolytic effects and easier discontinuation compared to shorter-acting agents. 1, 3

• Clonazepam reaches peak plasma concentrations in 1-4 hours with approximately 90% bioavailability. 1
• The longer elimination half-life reduces rebound anxiety and withdrawal severity compared to high-potency, short-acting benzodiazepines like alprazolam. 3, 4
• Alternative options include lorazepam (intermediate-acting, 8-15 hour half-life) or diazepam (long-acting, 20-120 hour half-life), though diazepam has active metabolites that may accumulate. 5, 2

Dosing Strategy

• Start with clonazepam 0.5-1 mg/day, with a maximum recommended dose of 2 mg/day if treatment exceeds 1 week. 3
• The mean effective dose in clinical trials was 2.3 mg/day for flexible dosing regimens. 1
• Use the lowest effective dose for the shortest duration possible to minimize receptor downregulation. 6

Duration of Treatment

Prescribe benzodiazepines for acute episodes only, limiting courses to 2-4 weeks maximum, with consideration for single-dose, intermittent, or very short (1-7 day) courses. 2

• The FDA notes that efficacy beyond 9 weeks has not been systematically studied in controlled trials, and physicians should periodically reevaluate long-term necessity. 1
• Approximately 50% of patients prescribed benzodiazepines for ≥12 months develop dependence due to GABA-A receptor downregulation. 6
• Long-term naturalistic data suggest that tolerance to antipanic effects does not typically occur with clonazepam, and doses may actually decrease over time in responders. 4, 7

Critical Safety Considerations

Benzodiazepines carry no cardiac arrhythmia risk and do not prolong QT interval, making them safe from a cardiovascular standpoint for patients with palpitations. 8

• In vitro studies show both inhibition and activation of potassium currents, but no QT changes occur in clinical use. 8
• However, benzodiazepines cause drowsiness, cognitive deficits, and are an independent risk factor for falls, especially in elderly patients. 8
• Respiratory depression can occur when combined with opioids or other CNS depressants. 9

Special Populations

• Elderly patients require dose reduction due to significantly increased sensitivity to benzodiazepine effects and higher risk of falls and cognitive impairment. 9, 5
• Patients with hepatic dysfunction have reduced clearance and require dose adjustment. 5, 1
• Clonazepam is safer than midazolam or diazepam in renal impairment, as it lacks problematic active metabolites. 9, 5

Discontinuation Protocol

Careful tapering is essential to minimize withdrawal symptoms, which can include severe rebound anxiety due to reduced GABA-A receptor function. 6

• Withdrawal symptoms occur after short-term alprazolam treatment; less data exists for clonazepam, though its longer half-life theoretically facilitates easier discontinuation. 4, 7
• Physical and psychological withdrawal can be severe, particularly with higher doses or longer treatment duration. 6

Clinical Pitfalls to Avoid

• Do not use benzodiazepines as monotherapy for chronic anxiety disorders—they should be combined with psychological treatments or antidepressants for sustained benefit. 2
• Avoid prescribing high-potency, short-acting agents like triazolam, which carry greater risks of adverse effects and rebound anxiety. 2, 3
• Do not overlook hepatic or renal function when selecting agents and dosing. 9, 5
• Monitor for signs of tolerance (requiring higher doses for same effect), which indicates receptor downregulation is occurring. 6