Rebound Headache

Aka: Rebound Headache, Rebound Migraine, Analgesic Overuse Headache, Medication Overuse Headache, Analgesic Rebound Headache

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II. Definitions

  1. Medication Overuse Headache
    1. Headache on 15 or more days of the month with known preexisting Primary Headache AND
    2. Regular overuse of abortive Headache medication over 3 months
      1. Opioids, Ergotamine and Triptans >10 days/month
      2. Nonopiate Analgesics (e.g. NSAIDS, Excedrin) >15 days per month

III. Epidemiology

  1. Accounts for 30-50% of chronic Headache patients
    1. See Chronic Non-Progressive Headache

IV. Pathophysiology

  1. Excessive use of Migraine Abortive Treatment medication
    1. Use more than 15-20 days per month confers risk
    2. Butalbital (Fiorinal) >5 days/month
    3. Opioids >8 days/month
    4. Triptans >10 days/month
    5. Nonopiate Analgesics (e.g. NSAIDS, Excedrin) >15 days per month
  2. Drug dependent pattern of Headaches
  3. Increasing tolerance to Headache medication dosages
  4. Medications most prone to Rebound Headache
    1. Occurs with all Headache medications
    2. Butalbital (e.g. Fiorinal): 47%
    3. Acetaminophen: 45%
    4. Opioid Analgesics: 31%
    5. Aspirin: 24%
    6. NSAIDs: 19%
    7. Excedrin: 18%
    8. Ergot alkaloids: 16%
    9. Triptans: 9%
    10. Medications containing Caffeine
    11. Bigal (2004) Cephalgia 24:483-90 [PubMed]

V. Symptoms

  1. Characteristics
    1. Variable type, severity, and location of Headache
  2. Timing
    1. Occur in the early morning (2am - 5am) daily
  3. Palliative
    1. Headaches resolve after Pain Medication discontinued
    2. Refractory to prophylactic medications
  4. Provocative factors
    1. Headache is easily precipitated
    2. Withdrawal symptoms on stopping Pain Medications
  5. Associated features
    1. Nausea and other gastrointestinal symptoms
    2. Asthenia
    3. Anxiety
    4. Depression
    5. Irritability
    6. Memory and concentration problems
    7. Neck Pain
    8. Vasomotor symptoms (Rhinorrhea, nasal congestion)
  6. Common presentations
    1. Often presents to ER requesting Opioids

VI. Diagnosis: Medication Overuse Headache

  1. Questions
    1. "Do you take a treatment for Headache attacks on more than 10 days per month?"
    2. "Do you do this on a regular basis?"
  2. Interpretation: Identifies Medication Overuse Headache in patient with frequent Migraine
    1. Test Sensitivity: 95.2%
    2. Test Specificity: 80%
  3. References
    1. Dousset (2013) J Headache Pain 14:81 [PubMed]

VII. Diagnosis: Drug Use Disorder

  1. Drug use disorder is commonly comorbid
  2. Questions
    1. "How many times in a year have used an illegal drug or used a prescription medication for non-medical use?"
  3. Interpretation: Drug Use Disorder
    1. Test Sensitivity: 100%
    2. Test Specificity: 74%
  4. References
    1. Smith (2010) Arch Intern Med 170(13):1155-60 [PubMed]

VIII. Management: Preferred Protocols

  1. Analgesic Withdrawal
    1. Most medications may be stopped abruptly
      1. Non-Opioid Analgesics (e.g. nsaids)
      2. Triptans
    2. Gradually taper over 5 weeks (risk of withdrawal)
      1. Opioids
      2. Barbiturates
      3. Ergot alkaloids
      4. Benzodiazepines
      5. Caffeine
  2. Provide non-Opioid rescue medications during withdrawal
    1. Antiemetics (Metoclopramide, Promethazine)
    2. Antihistamines (Diphenhydramine or Hydroxyzine)
    3. Most effective adjunctive withdrawal agents
      1. Prednisone 60 mg daily for 5 days (caution, due to adverse effects)
      2. Migraine Prophylaxis agents
        1. Topiramate (Topomax) 100-200 mg daily
        2. Amitriptyline 50 mg daily
      3. References
        1. Evers (2011) Eur J Neurol 18(9): 1115-21 [PubMed]
  3. Initiate Headache prophylaxis simultaneously with withdrawal
    1. Decreases Headache frequency and sustains resolution of Medication Overuse Headaches
    2. Beta blocker Migraine Prophylaxis was used in this study
    3. Carlsen (2020) JAMA Neurol 77(9): 1069-78 [PubMed]
  4. Other measures with limited evidence
    1. Consider switching from Triptan to Rimegepant or Ubrogepant
    2. Botulinum Toxin Injection
    3. Valproate
    4. Munksgaard (2019) Acta Neurol Scand 139(5): 405-14 [PubMed]

IX. Management: Older Withdrawal Regimens (use with caution)

  1. Displayed for historical purposes and for additional strategies
  2. Many of the medications listed here have been replaced (e.g. fiorinal, Ergotamine)
  3. Withdrawal from Simple Analgesics
    1. Protocol
      1. Choose 1 medication from Group A and B
      2. Take bridge medication (Group B) on schedule
      3. Take rescue medication (Group A) as needed
        1. Only use for severe Headache
        2. Limit to twice weekly
    2. Group A: Rescue - Migraine specific medications
      1. Dihydroergotamine (DHE) or
      2. Long-acting Triptan (e.g. Amerge, Frova) or
      3. Midrin 1 PO tid for 1 week
    3. Group B: Bridge - Antiinflammatory medications
      1. NSAIDs for 3-6 weeks on schedule
        1. Naproxen 500 mg bid
        2. Nabumetone 750 mg/day
      2. Prednisone protocol
        1. Prednisone 60 mg qd for 2 days then
        2. Prednisone 40 mg qd for 2 days then
        3. Prednisone 20 mg qd for 2 days then
        4. Consider Ranitidine concurrently with Prednisone
          1. Dose: 150 mg PO bid for 6 days
      3. Triptan (not FDA approved)
        1. Use bid until 48 hours Headache-free (10 day max)
    4. Group C: Miscellaneous medications to consider
      1. Start Elavil at bedtime
      2. Cyproheptadine (Periactin) 4 mg PO tid
    5. References
      1. Maizels (2004) Am Fam Physician 70:2299-6 [PubMed]
  4. Withdrawal from Butalbital medication (e.g. Fiorinal)
    1. Consider Detoxification program
      1. Indicated for more than 8 Butalbital pills per day
    2. Midrin or Periactin at doses above
    3. Phenergan 25-50 mg tid prn for 1 to 2 weeks
    4. Clonazepam 0.5-1.0 mg PO for 1 week, then taper
    5. Phenobarbital 30 mg PO tid for 1 week
  5. Withdrawal from Ergotamine medications
    1. Consider inpatient withdrawal
      1. Indicated for more than 1.0 mg Ergotamine per day
    2. Naproxen (Anaprox) 500-1000 mg daily for 1-3 weeks
    3. Methylergonovine (Methergine) 0.2-0.4 mg tid
    4. Phenergan 25-50 mg tid for 1-2 weeks
  6. Withdrawal from Codeine containing Analgesics
    1. Clonidine 0.1-0.2 mg tid for 1-2 weeks, then taper
    2. Naproxen 500-1000mg qd for 1-3 weeks
    3. Promethazine 25-30 mg tid prn for 1-2 weeks

X. Prevention

  1. Maximize Migraine Prophylaxis
  2. Limit acute Migraine abortive medications to 10 days per month or 2 days per week
  3. Long acting NSAIDs may be less likely than other simple Analgesics to cause Rebound Headaches
  4. Avoid butalbital (fiorinal) for Headaches
  5. Get control of Migraine Headaches soon after episode onset (e.g. start Triptan at higher, effective dose early)

XI. Reference

  1. (2022) Presc Lett 29(4): 19-20
  2. Mathew (1997) Neurol Clin 15(1):167-86 [PubMed]
  3. Millea (2002) Am Fam Physician 66:797-805 [PubMed]
  4. Walling (2020) Am Fam Physician 101(7):419-28 [PubMed]

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