What does the 2021 Malaysian Society of Neurosciences consensus recommend for acute and preventive treatment of adult primary headaches (migraine, tension‑type, and cluster) and how to avoid medication‑overuse headache?

Malaysian Society of Neurosciences 2021 Consensus on Headache Management

Acute Treatment of Migraine

First-Line Therapy for Mild-to-Moderate Migraine

• NSAIDs are the recommended first-line treatment for mild-to-moderate migraine attacks, including ibuprofen 400–800 mg, naproxen sodium 500–825 mg, or aspirin 1000 mg. 1
• Combination therapy with acetaminophen 1000 mg + aspirin 500–1000 mg + caffeine 130 mg achieves pain reduction to mild or none in 59.3% of patients at 2 hours. 1
• Treatment should begin as early as possible during the attack while pain is still mild, because early administration results in ≈50% of patients becoming pain-free at 2 hours versus ≈28% when treatment is delayed until pain is moderate or severe. 1

First-Line Therapy for Moderate-to-Severe Migraine

• Triptans are first-line therapy for moderate-to-severe migraine attacks, with oral options including sumatriptan 50–100 mg, rizatriptan 10 mg, eletriptan 40 mg, zolmitriptan 2.5–5 mg, and naratriptan. 1
• The combination of sumatriptan 50–100 mg plus naproxen 500 mg is superior to either agent alone, yielding 130 additional patients per 1,000 who achieve sustained pain relief at 48 hours compared with sumatriptan alone. 1
• Subcutaneous sumatriptan 6 mg provides the highest efficacy among all triptan formulations, achieving complete pain relief in approximately 59% of patients within 2 hours and onset of action within 15 minutes. 1
• Intranasal sumatriptan 5–20 mg or other nasal spray triptans are particularly useful when significant nausea or vomiting is present. 1

Adjunctive Antiemetic Therapy

• Metoclopramide 10 mg IV or prochlorperazine 10 mg IV should be administered 20–30 minutes before or concurrently with NSAIDs or triptans to treat nausea and provide synergistic analgesia. 1
• Metoclopramide provides direct analgesic effects for migraine pain through central dopamine receptor antagonism, independent of its antiemetic properties. 1
• Metoclopramide is contraindicated in patients with pheochromocytoma, seizure disorders, active gastrointestinal bleeding, or gastrointestinal obstruction. 1

Parenteral Therapy for Severe or Refractory Migraine

• The recommended IV cocktail for severe migraine in urgent care or emergency settings consists of ketorolac 30 mg IV plus metoclopramide 10 mg IV, providing rapid pain relief with minimal risk of rebound headache. 1
• Dihydroergotamine (DHE) 0.5–1.0 mg IV has good evidence for efficacy as monotherapy for acute migraine when NSAIDs are contraindicated, and can be repeated every hour up to a maximum of 2 mg IV per day. 1
• DHE is contraindicated in patients using triptans within the past 24 hours, taking beta-blockers, with uncontrolled hypertension, coronary artery disease, pregnancy, or sepsis. 1

Alternative Acute Therapies When Triptans Are Contraindicated

• CGRP antagonists (gepants) such as ubrogepant 50–100 mg or rimegepant are the primary oral alternative for moderate-to-severe migraine when triptans are contraindicated, due to their lack of vasoconstriction and safety in patients with cardiovascular disease. 1
• Lasmiditan (Reyvow) 50–200 mg is a 5-HT1F receptor agonist without vasoconstrictor activity, making it safe for patients with cardiovascular disease, but patients must not drive or operate machinery for at least 8 hours after administration due to CNS effects. 1
• Triptans are contraindicated in patients with ischemic heart disease, previous myocardial infarction, coronary artery vasospasm, uncontrolled hypertension, cerebrovascular disease, history of stroke or TIA, or basilar/hemiplegic migraine. 1

Medications to Avoid in Acute Migraine Treatment

• Opioids (including codeine, hydromorphone, oxycodone) and butalbital-containing compounds should not be used for migraine treatment because they have limited efficacy, carry a two-fold higher risk of medication-overuse headache compared with NSAIDs and triptans, lead to dependency, and result in poorer long-term outcomes. 1
• When an opioid is deemed absolutely necessary after all evidence-based options have failed, butorphanol nasal spray has better evidence than other opioids for headache treatment. 1

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Prevention of Medication-Overuse Headache (MOH)

Critical Frequency Limitation

• All acute migraine medications must be limited to no more than 2 days per week (≤10 days per month) to prevent medication-overuse headache, which can paradoxically increase headache frequency and lead to daily headaches. 1, 2
• Medication-overuse headache occurs when NSAIDs or acetaminophen are used on ≥15 days per month, or when triptans, ergots, or combination analgesics are used on ≥10 days per month. 1, 2
• Daily use of a triptan for more than 2 days per week creates a self-perpetuating cycle that sustains chronic migraine. 1

Recognition and Diagnosis of MOH

• MOH is diagnosed when a patient with a pre-existing headache disorder has headache on ≥15 days per month while regularly overusing acute medication for >3 months. 1
• Patients with MOH usually have a long history of primary headache, overuse of medications, and MOH before they consult a physician for care. 2

Management of Established MOH

• Abrupt cessation of both the overused triptan and NSAID is recommended; evidence does not support a gradual taper. 1
• Patients should be warned that headache intensity may temporarily worsen for 2–10 days during withdrawal. 1
• Substituting another acute medication during the withdrawal period is discouraged because it merely transfers the overuse to a different agent. 1
• Once MOH resolves (typically 2–4 weeks after discontinuation), acute treatment should be reserved for the most severe, disabling attacks and limited to ≤2 days per week. 1

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Preventive Treatment of Migraine

Indications for Initiating Preventive Therapy

• Preventive therapy is recommended for patients who experience ≥2 migraine attacks per month with disability lasting ≥3 days, who use abortive medication >2 times per week, who have contraindications to or failure of acute treatments, or who have uncommon migraine subtypes. 1, 3
• Additional factors prompting preventive treatment include significant adverse events from acute therapies, strong patient preference for prevention, and cost considerations. 3
• If headaches continue to impair quality of life despite optimized acute therapy, or if the patient uses acute medications more than 2 days per week, preventive therapy is indicated. 1

First-Line Preventive Medications

Beta-Blockers

• Propranolol 80–240 mg/day and timolol 20–30 mg/day are FDA-approved first-line preventive medications with strong evidence for efficacy from multiple randomized controlled trials. 3
• The typical effective dose of propranolol is 160 mg once daily, with some patients requiring up to 240 mg daily; doses below 160 mg are generally sub-therapeutic. 3
• Alternative beta-blockers with moderate evidence include metoprolol, atenolol, and nadolol. 3

Topiramate

• Topiramate 50–100 mg/day (typically 50 mg twice daily) is a first-line preventive medication with strong randomized controlled trial evidence for both episodic and chronic migraine. 3
• Topiramate is the only oral preventive agent with strong RCT evidence specifically confirming efficacy in chronic migraine. 3
• In patients with obesity, topiramate is preferred because it promotes weight loss, providing an additional therapeutic benefit. 3

Candesartan

• Candesartan is an effective first-line agent with strong evidence from randomized controlled trials, particularly useful for patients with comorbid hypertension. 3

Second-Line Preventive Medications

Amitriptyline

• Amitriptyline 30–150 mg/day is a second-line preventive medication preferred for patients with comorbid depression, anxiety, or sleep disturbances, as it can address both migraine and mood disorders simultaneously. 3
• Amitriptyline lacks robust RCT evidence for chronic migraine prophylaxis; its efficacy is primarily demonstrated in episodic migraine and mixed migraine plus tension-type headache. 3
• Amitriptyline shows greatest efficacy at daily doses ranging from 30 mg to 150 mg, with higher doses within this range often needed to achieve adequate response. 3

Sodium Valproate/Divalproex Sodium

• Sodium valproate 800–1500 mg/day or divalproex sodium 500–1500 mg/day are second-line options with moderate evidence for efficacy. 3
• Valproate and divalproex sodium are strictly contraindicated in women of childbearing potential due to teratogenic risk, and contraception counseling is mandatory. 3
• Common adverse effects include weight gain, hair loss, tremor, and teratogenic potential. 3

Flunarizine

• Flunarizine 5–10 mg once daily (typically at night) is an effective second-line agent with proven efficacy comparable to propranolol and topiramate, supported by multiple placebo-controlled trials. 3
• Common adverse effects include sedation and daytime tiredness, weight gain, and abdominal pain. 3
• Serious adverse effects, particularly in the elderly, include depression and extrapyramidal symptoms. 3
• Absolute contraindications include active Parkinsonism or history of extrapyramidal disorders, and current depression is a relative contraindication. 3

Third-Line Preventive Medications

CGRP Monoclonal Antibodies

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) should be considered when two or three oral preventive medications have failed or are contraindicated. 3
• These agents are administered monthly via subcutaneous injection, with efficacy requiring assessment after 3–6 months. 3
• CGRP monoclonal antibodies are significantly more expensive than oral agents, with an annualized cost of $5,000–$6,000. 3

OnabotulinumtoxinA (Botox)

• OnabotulinumtoxinA is the only FDA-approved preventive therapy specifically for chronic migraine (not episodic migraine) and should be used as first-line when three oral preventives have failed. 1, 3
• Phase III PREEMPT trials demonstrated that onabotulinumtoxinA reduces headache days, headache episodes, cumulative headache hours, and improves quality of life in chronic migraine patients. 1
• The recommended administration protocol is 155–195 U injected across 31–39 sites every 12 weeks, performed by a neurologist or headache specialist. 1
• Efficacy should be evaluated after 6–9 months of treatment to determine success or failure. 1, 3

Implementation of Preventive Therapy

• An oral preventive agent should be trialed at its target dose for 2–3 months before judging efficacy, because clinical benefits may not become apparent until this period has elapsed. 3
• Start with a low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases. 3
• Use headache diaries to track attack frequency, severity, duration, disability, treatment response, and adverse effects. 3
• Consider pausing preventive treatment after 6–12 months of successful therapy to determine if it can be discontinued. 3

Non-Pharmacological Preventive Options

• Cognitive behavioral therapy, biofeedback, and relaxation training should be offered alongside medication as effective adjuncts for migraine prevention. 3
• Neuromodulatory devices can be considered as adjuncts to medication or as stand-alone treatments when medications are contraindicated. 3
• Identifying and modifying triggers such as sleep hygiene, regular meals, hydration, and stress management can reduce migraine frequency. 3

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Acute Treatment of Tension-Type Headache

First-Line Therapy

• NSAIDs (ibuprofen 400–800 mg, naproxen 500–825 mg) are the mainstay treatment for tension-type headache. 4
• Acetaminophen 1000 mg is the safest first-line analgesic for intermittent headache when hypertension is uncontrolled, because it does not raise blood pressure or cardiovascular risk. 1
• A 1000 mg dose of acetaminophen provides statistically significant improvement in pain-free response at 2 hours for tension-type headache, with a number-needed-to-treat of 22 compared with placebo. 1

Preventive Therapy for Chronic Tension-Type Headache

• Tricyclic antidepressants (amitriptyline 30–150 mg/day) have the most evidence as prophylactic therapy for tension-type headache. 4

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Acute Treatment of Cluster Headache

First-Line Therapy

• Subcutaneous sumatriptan 6 mg provides the highest efficacy for acute cluster headache attacks, achieving onset of action within 15 minutes. 1
• Intranasal sumatriptan 5–20 mg is an effective alternative when subcutaneous administration is not feasible. 1
• High-flow oxygen (100% oxygen at 12–15 L/min via non-rebreather mask for 15–20 minutes) is a first-line abortive treatment for cluster headache. 5

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Common Pitfalls and Caveats

Diagnostic Pitfalls

• Migraine is underdiagnosed; it is reasonable to err on the side of migraine when choosing between primary headaches. 6
• Neuroimaging (CT or MRI) should be performed only when red-flag findings are present, including thunderclap onset, atypical aura, recent head trauma, fever, impaired memory, focal neurological deficits, abnormal vital signs, progressive worsening, or new-onset headache after age 50. 1

Treatment Pitfalls

• Do not maintain sub-therapeutic doses of preventive medications (e.g., propranolol <160 mg or amitriptyline <30 mg) indefinitely; doses should be optimized before declaring treatment failure. 3
• Do not discontinue preventive therapy prematurely; an adequate trial requires 2–3 months at the target dose before assessing response. 3
• Do not allow patients to increase frequency of acute medication use in response to treatment failure, as this creates a vicious cycle of medication-overuse headache; instead transition to preventive therapy while optimizing acute treatment strategy. 1
• Failure of one triptan does not predict failure of others; if one triptan is ineffective after 2–3 headache episodes, try a different triptan before escalating to third-line agents. 1
• Routine neuroimaging for typical recurrent migraine without red flags is discouraged to avoid unnecessary radiation, cost, and incidental findings that may trigger further unnecessary investigations. 1

Special Populations

• In elderly South East Asian patients, tension-type headache is the commonest subtype (45.7%), while chronic daily headache is more prevalent in elderly patients compared to younger patients (47.1% vs. 28.4%). 7
• Screening and treating obstructive sleep apnea can reduce migraine frequency. 3
• Weight loss can reduce migraine frequency in patients with obesity. 3