Is amitriptyline (tricyclic antidepressant) safe to use in patients with a concussion?

Amitriptyline Use in Concussion Patients

Amitriptyline can be used safely in concussion patients for post-traumatic headache, with evidence showing it is well-tolerated and effective, though compliance and response rates vary. 1, 2

Evidence for Use in Post-Concussive Headache

Amitriptyline is the most studied pharmacologic intervention for post-traumatic headache following concussion, with specific data in adolescent and adult populations:

• In adolescent concussion patients (ages 13-18), 82% reported beneficial effects from amitriptyline for post-traumatic headache, with the medication being well-tolerated 1
• Females are more likely to be prescribed amitriptyline (24% vs 13% in males) and have longer recovery times overall (median 80 days vs 34 days), though this reflects disease severity rather than medication effects 1
• Amitriptyline shows short-term symptom improvements with sustained effects over time, though long-term outcomes are similar to natural recovery 2

Dosing and Administration Specifics

Start with 10-25 mg at bedtime and titrate gradually to minimize adverse effects, which is critical in the concussion population:

• Initial dose: 10-25 mg nightly 3, 4
• Target dose for neuropathic pain conditions: 75-150 mg daily or 1-1.5 mg/kg at bedtime 3, 4
• Slow titration (10-25 mg increments every 2 weeks) improves tolerability 3
• Maximum dose should not exceed 150 mg/day 4

Safety Considerations in Concussion Patients

The brain-injured population may be more susceptible to medication side effects, requiring careful monitoring:

• Most common adverse effects include somnolence, dry mouth, blurred vision, constipation, and weight gain 3, 4
• Obtain screening ECG in patients over 40 years due to risk of QTc prolongation and cardiac conduction abnormalities 3
• Orthostatic hypotension and tachycardia can occur, particularly problematic in elderly patients 5
• Contraindicated in patients with ischemic cardiac disease, stroke, peripheral vascular disease, uncontrolled hypertension, or decompensated heart failure 4

Clinical Effectiveness and Limitations

While amitriptyline shows benefit for post-concussive headache, compliance is a significant challenge in this population:

• Younger patients (mean age 32.7 years) show particularly poor medication compliance, with 49% of assigned patients taking no medication throughout treatment 6
• Therapeutic effect may take up to 30 days to develop, though sedative effects appear earlier 4
• Depression following head injury may be relatively resistant to tricyclic therapy compared to functional depression 7
• Headache diary compliance is also problematic (only 58% meet daily entry completion), making outcome assessment difficult 6

Practical Algorithm for Use

Follow this stepwise approach when considering amitriptyline for post-concussive headache:

1. Screen for cardiac contraindications (obtain ECG if age >40 years, assess for ischemic disease, conduction abnormalities) 3, 4
2. Assess headache severity and impact: Consider pharmacologic treatment if headaches are severe, debilitating, or persistent beyond 2-4 weeks 3
3. Start low dose (10 mg nightly) and counsel patient on expected timeline (30 days for full effect) 4, 6
4. Titrate slowly (10-25 mg every 2 weeks) to target dose of 75-150 mg based on response and tolerability 3, 4
5. Monitor closely for adverse effects, particularly sedation, anticholinergic symptoms, and orthostatic hypotension 5
6. Reassess at 6-8 weeks (including 2 weeks at highest tolerated dose) for adequate trial 3

Key Clinical Pitfalls

Avoid these common errors when prescribing amitriptyline for concussion:

• Do not assume medication non-response without addressing compliance first—nearly half of patients may not take prescribed medication 6
• Do not use in patients with cardiac disease without cardiology consultation 3, 4
• Do not expect immediate results—counsel patients that full therapeutic effect requires 4-6 weeks 4
• Do not overlook age-related risks—elderly patients have increased risk of confusion, falls, and cardiovascular effects 3, 5
• Do not prescribe without establishing realistic expectations—natural recovery occurs over time regardless of medication 2, 6