Is melatonin effective for treating anxiety and chest pain?

Melatonin for Anxiety and Chest Pain

Melatonin may be effective for anxiety but is not recommended as a primary treatment for chest pain, as there is insufficient evidence supporting its use for this specific indication.

Efficacy for Anxiety

Evidence for Anxiety Treatment

• Melatonin has demonstrated anxiolytic properties in clinical studies, particularly in the perioperative setting. A Cochrane review concluded that preoperative melatonin can reduce anxiety compared to placebo in adults and may be as effective as midazolam 1.
• When used preoperatively, melatonin probably reduces anxiety measured 50-120 minutes after administration (mean difference -11.69 on a 0-100mm VAS compared to placebo), which is potentially clinically relevant 2.
• Melatonin appears to have similar anxiolytic effects to benzodiazepines but with a more favorable side effect profile, particularly regarding psychomotor and cognitive function 2.

Mechanism of Action for Anxiety

• Melatonin mediates its anxiolytic effects through multiple pathways including:
  • MT1/MT2 melatonin receptors
  • GABA-B receptors
  • Interaction with the renin-angiotensin and glucocorticoid systems
  • Antioxidant and radical scavenging properties 3
• The anxiolytic effects may also be related to melatonin's ability to improve sleep quality, which can indirectly reduce anxiety levels 4.

Efficacy for Chest Pain

Evidence for Chest Pain Treatment

• There is insufficient evidence supporting melatonin specifically for chest pain management.
• For patients with recurrent chest pain presentations with no evidence of physiological cause after negative cardiac workup, cognitive-behavioral therapy is recommended rather than medication approaches 1.
• The American College of Cardiology/American Heart Association guidelines make no mention of melatonin as a treatment option for chest pain 1.

Alternative Approaches for Chest Pain with Anxiety Component

• For patients with chest pain associated with anxiety where cardiac causes have been ruled out, cognitive-behavioral therapy is recommended (Class 2a, Level B-R evidence) 1.
• Studies show that in low-risk chest pain patients without evidence of cardiac disease, depression, anxiety, and gastroesophageal syndromes each exceeded coronary artery disease by almost 10-fold 1.
• A systematic review of psychotherapy (17 RCTs) for patients with non-cardiac chest pain revealed a 32% reduction in chest pain frequency with cognitive-behavioral approaches being most effective 1.

Safety Profile

• Melatonin is generally considered safe with few mild to moderate adverse events in adults 5.
• Most commonly reported adverse events include:
  • Daytime sleepiness (1.66%)
  • Headache (0.74%)
  • Other sleep-related adverse events (0.74%)
  • Dizziness (0.74%)
  • Hypothermia (0.62%) 5
• No life-threatening or major clinical adverse events have been identified in clinical trials 5.
• Melatonin has been shown to be safe in the perioperative period 1.

Dosing Considerations

• Typical doses used in clinical studies range from 0.15 mg to 12 mg daily 5.
• For anxiety, particularly in perioperative settings, doses of 3-10 mg have been studied 2.
• The American Academy of Sleep Medicine recommends 1-5 mg for adults with sleep disorders 6.
• Administration is typically 1-2 hours before bedtime 6.

Clinical Application Algorithm

1. For patients with anxiety without chest pain:

   • Consider melatonin (3-5 mg) 1-2 hours before bedtime if anxiety is associated with sleep disturbances
   • Monitor for effectiveness after 1-2 weeks
   • If inadequate response, consider referral for cognitive-behavioral therapy

2. For patients with chest pain and anxiety:

   • First rule out cardiac and other physiological causes of chest pain
   • If chest pain is determined to be non-cardiac:
     • Refer for cognitive-behavioral therapy (preferred approach)
     • Consider melatonin only as an adjunct for sleep disturbances associated with anxiety, not as primary treatment for chest pain

3. For patients with recurrent, similar presentations of chest pain with negative cardiac workup:

   • Refer to cognitive-behavioral therapy (Class 2a recommendation) 1
   • Do not rely on melatonin as primary treatment for the chest pain symptoms

Important Caveats

• The Society for Integrative Oncology-ASCO guideline found inconsistent results for melatonin's effect on anxiety in cancer patients 1.
• The American Academy of Sleep Medicine suggests against using melatonin for insomnia treatment in adults due to weak evidence supporting efficacy 1.
• There is insufficient evidence from long-term randomized controlled trials regarding the safety of continuous melatonin therapy over extended periods 5.
• Melatonin should not be considered a replacement for proper medical evaluation of chest pain, which could represent serious underlying conditions.