What are the long-term side effects of cyclobenzaprine (Flexeril)?

Long-Term Side Effects of Cyclobenzaprine (Flexeril)

Cyclobenzaprine has significant potential for long-term side effects including sedation, anticholinergic effects, and risk of serotonin syndrome when used beyond the recommended short-term duration (2-3 weeks). 1, 2

Common Long-Term Side Effects

Neurological Effects

• Drowsiness/sedation (occurs in 29-38% of patients) 2
• Dizziness (3-11% of patients) 2
• Fatigue (6% of patients) 2
• Mental acuity decrease 2
• Headache (5% of patients) 2
• Confusion 2

Anticholinergic Effects

• Dry mouth (21-32% of patients) 2
• Blurred vision 2
• Constipation (1-3% of patients) 2
• Urinary retention 2

Serious Long-Term Concerns

Cardiovascular Effects

• Tachycardia 2
• Arrhythmias 2
• Palpitations 2
• Hypertension or hypotension 2, 3
• Potential for heart block and conduction disturbances 2

Serotonin Syndrome Risk

• Life-threatening serotonin syndrome when combined with:
  • SSRIs
  • SNRIs
  • TCAs
  • Tramadol
  • Bupropion
  • MAO inhibitors (contraindicated)
  • Meperidine
  • Verapamil 2

Hepatic Effects

• Abnormal liver function
• Rare reports of hepatitis, jaundice, and cholestasis 2

Dependency and Withdrawal

• Potential for physical and psychological dependence 4
• Withdrawal symptoms may occur if discontinued abruptly after long-term use 1
• Tapering is recommended over 2-3 weeks to prevent withdrawal symptoms 1

Mechanism of Side Effects

Cyclobenzaprine's side effect profile is related to its structural similarity to tricyclic antidepressants 2, 4. Recent research has identified that cyclobenzaprine is a potent non-competitive antagonist of histamine H1 receptors, which likely explains its significant sedative effects 5.

Risk Factors for Increased Side Effects

• Age (elderly patients are more susceptible to side effects) 1
• Liver or kidney impairment 1
• History of substance abuse 1
• Concomitant use of CNS depressants 2
• Hyperthyroidism 1
• Cardiac conditions 1, 2

Recommendations for Long-Term Use

1. Avoid long-term use whenever possible

   • Limit treatment duration to ≤21 days 1
   • No evidence supports efficacy beyond 2-3 weeks 1

2. If long-term use is necessary:

   • Use lowest effective dose (5 mg TID preferred over 10 mg TID) 6
   • Monitor for side effects regularly 1
   • Consider drug holidays
   • Implement non-pharmacological approaches (physical therapy, exercise) 1

3. When discontinuing after long-term use:

   • Taper over 2-3 weeks 1
   • Reduce dose by 25-30% in week 1
   • Reduce by 50% in week 2
   • Reduce by 25% in week 3 before complete discontinuation 1

Contraindications for Long-Term Use

• MAO inhibitor use (current or within 14 days) 1, 2
• Acute recovery phase of myocardial infarction 1, 2
• Heart block or conduction disturbances 1, 2
• Arrhythmias 1, 2
• Hyperthyroidism 1, 2
• Co-prescription with benzodiazepines (increased risk of respiratory depression) 1

Monitoring During Long-Term Use

• Regular assessment of continued need for therapy
• Monitoring for cardiovascular effects
• Liver function tests if clinically indicated
• Assessment for dependency or misuse
• Evaluation of sedation impact on daily functioning

While cyclobenzaprine is effective for short-term muscle spasm relief, its structural similarity to tricyclic antidepressants and significant side effect profile make it problematic for long-term use. The risk-benefit ratio becomes increasingly unfavorable with extended duration of treatment.