How should medication‑overuse (rebound) headaches be managed?

Management of Medication-Overuse (Rebound) Headaches

Abrupt withdrawal of the overused medication is the necessary and only remedy for medication-overuse headache, and preventive therapy should be started on the first day of withdrawal or even before stopping the offending drug. 1

Recognizing Medication-Overuse Headache

Medication-overuse headache (MOH) develops when acute headache medications are used too frequently in patients with a pre-existing primary headache disorder. 2, 1 The diagnostic thresholds are:

• ≥15 days per month for NSAIDs, acetaminophen, or combination analgesics 2, 1
• ≥10 days per month for triptans, ergotamines, or opioids 2, 1
• Duration of overuse >3 months 2, 1

The headache occurs on ≥15 days per month and has developed or worsened during medication overuse. 2 Importantly, MOH can only be confirmed retrospectively after successful withdrawal—diagnosis requires observation for at least 2-3 months following medication cessation. 1, 3

Immediate Withdrawal Strategy

Abrupt cessation is preferred over gradual tapering for all medications except opioids, benzodiazepines, and barbiturates, which require supervised tapering to prevent dangerous withdrawal syndromes. 1, 4 The evidence shows that complete cessation is more feasible and effective than restricted intake, with a 44% reduction in medication dependence. 1

Critical patient counseling: Warn patients explicitly that headaches will worsen for 2-10 days during withdrawal before improvement begins—this temporary worsening does not indicate treatment failure. 5, 1 Withdrawal symptoms (nausea, anxiety, sleep disturbance) are expected and transient. 4, 6

Do not substitute another acute medication during the withdrawal period, as this merely transfers the overuse to a different agent and perpetuates the cycle. 5

Concurrent Preventive Therapy

Preventive medication should be initiated on day 1 of withdrawal or even before stopping the overused medication—do not wait for withdrawal to complete. 1, 4 This parallel approach improves success rates and reduces relapse. 1

First-Line Preventive Options:

• Topiramate (titrated to therapeutic dose) has the strongest evidence for chronic migraine after MOH 1, 4
• OnabotulinumtoxinA (Botox) 155-195 units across 31-39 sites every 12 weeks is FDA-approved specifically for chronic migraine and should be used when three oral preventives have failed 5
• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) for patients who have failed at least two other preventive medications, with efficacy assessed after 3-6 months 1
• Amitriptyline 30-150 mg/day for patients with comorbid depression, anxiety, or mixed migraine/tension-type headache 5
• Propranolol 80-240 mg/day or timolol 20-30 mg/day for patients without contraindications 5

Efficacy of preventive therapy requires 2-3 months for oral agents, 3-6 months for CGRP antibodies, and 6-9 months for onabotulinumtoxinA before determining success or failure. 5

Managing Withdrawal Symptoms

• Use prokinetic antiemetics (metoclopramide 10 mg or domperidone) for nausea/vomiting rather than additional analgesics 1
• Prednisone (60 mg/day for 2 days, 40 mg/day for 2 days, 20 mg/day for 2 days) or naratriptan 2.5 mg twice daily during the first 6 days reduces withdrawal symptoms and rescue medication consumption compared to no bridging therapy 6
• Maintain hydration, regular meals, sufficient sleep, and stress management 1

Post-Withdrawal Acute Medication Limits

Once MOH resolves (typically 2-4 weeks after discontinuation), acute treatment must be strictly limited to ≤2 days per week (approximately 8-10 days per month) to prevent recurrence. 5, 1 This limit is non-negotiable and applies to all acute agents—NSAIDs, triptans, combination analgesics, and antiemetics. 5

Reserve acute medications only for the most severe, disabling attacks. 5

Expected Timeline and Success Rates

• Days 1-10: Withdrawal phase with temporary headache worsening 5, 1
• Weeks 2-4: Baseline headache pattern becomes apparent 5
• Months 2-3: Evaluate response to preventive therapy for oral agents 1
• Months 3-6: Evaluate response for CGRP antibodies 1
• Months 6-9: Evaluate response for onabotulinumtoxinA 5

The success rate of this approach is 50-70% at 6-12 months, although patients with opioid-associated MOH have higher relapse rates. 1, 4 Close follow-up and patient education reduce relapse. 4

Setting of Care

Most patients can be managed in outpatient primary care settings unless addictive drugs (opioids, barbiturates, benzodiazepines) are involved, which may require inpatient detoxification. 1 Chronic migraine that persists after successful MOH treatment requires specialist referral. 1

Critical Pitfalls to Avoid

• Continuing daily acute medication use "because it works" perpetuates MOH and guarantees treatment failure 5
• Substituting opioids or butalbital compounds as rescue medications—these have the highest risk for MOH development and dependency 1
• Delaying preventive therapy while trialing multiple acute strategies undermines timely control 5
• Confusing chronic migraine with MOH—they often coexist but require different management approaches; MOH requires withdrawal first 1
• Abandoning treatment early—preventive efficacy requires several weeks to months and should not be judged prematurely 1

Prevention of Future MOH

• Initiate preventive therapy for patients with ≥2 headache days per week 2, 5
• Educate patients that frequent use of any acute medication (more than twice weekly) can cause increasing headache frequency and daily headaches 2, 5
• Maintain headache diaries to monitor medication use frequency and facilitate early detection of overuse patterns 5, 1
• Discourage anticipatory medication use and consider migraine-specific therapy early in the natural history 3