Migraine Medication: Complete Guide to Treatment Options

What Medications Are Used During a Migraine Attack?

During a migraine attack, medications include simple analgesics (paracetamol), NSAIDs (ibuprofen, aspirin, naproxen), triptans (sumatriptan, rizatriptan, eletriptan), antiemetics (metoclopramide), and newer gepants (rimegepant, ubrogepant). Taking medication early in the attack significantly improves effectiveness.

Acute migraine treatment aims to relieve pain and associated symptoms as quickly as possible. The key to successful treatment is taking medication early, ideally when symptoms first begin. Research consistently shows that medications are significantly more effective when taken in the early stages of an attack, before the pain becomes severe and before central sensitization develops.

The choice of acute medication depends on several factors: the severity and typical duration of your attacks, how quickly symptoms progress, whether you experience nausea or vomiting, your response to previous treatments, and any contraindications you may have. Many patients benefit from having different treatment options available for attacks of varying severity.

A stepped approach is commonly recommended: start with over-the-counter analgesics for mild attacks, and if these don't provide relief within an hour, move to a triptan. Alternatively, if you know from experience that your attacks are typically moderate to severe and don't respond to simple analgesics, starting with a triptan immediately may be more appropriate.

NSAIDs and Simple Analgesics

Non-steroidal anti-inflammatory drugs (NSAIDs) work by inhibiting cyclooxygenase (COX) enzymes, thereby reducing prostaglandin production. Prostaglandins are involved in both pain signaling and inflammation. For mild to moderate migraine attacks, NSAIDs are often effective and readily available without prescription.

Ibuprofen (400-600 mg) is widely used and generally well-tolerated. Aspirin (900-1000 mg) combined with caffeine has shown good efficacy in clinical trials, with the caffeine enhancing absorption and providing additional analgesic effect. Naproxen (500-750 mg) has a longer duration of action, which may help prevent headache recurrence. Diclofenac (50-100 mg) is another effective option, particularly in its fast-acting formulations.

Paracetamol (acetaminophen, 1000 mg) can be effective for mild attacks, though its mechanism in migraine is less clear than NSAIDs. It has a different side effect profile with fewer gastrointestinal risks but requires caution regarding maximum daily dose due to hepatotoxicity risk at higher doses.

Triptans: First-Line Treatment for Moderate-Severe Attacks

Triptans are selective serotonin (5-HT1B/1D) receptor agonists specifically developed for migraine treatment. They work through multiple mechanisms: causing vasoconstriction of dilated intracranial blood vessels, inhibiting the release of vasoactive neuropeptides from trigeminal nerve endings, and reducing pain signal transmission in the trigeminal nucleus caudalis.

Multiple triptans are available, and while they share the same basic mechanism, they differ in pharmacokinetic properties such as onset of action, bioavailability, and half-life. This means that patients who don't respond to one triptan may benefit from trying another.

Triptans should be taken once the headache phase has begun, not during the aura phase, as they are not effective when taken too early. If the first dose doesn't provide relief, taking a second dose is unlikely to help. However, if the first dose provides relief but the headache returns, a second dose can be taken after at least 2 hours.

Antiemetics for Nausea and Improved Absorption

Metoclopramide serves a dual purpose in migraine treatment. It directly combats nausea and vomiting, which affect many migraine patients, and it promotes gastric motility. During a migraine attack, gastric stasis (delayed gastric emptying) is common and can significantly impair the absorption of oral medications. By restoring normal gastric function, metoclopramide helps other medications work more effectively.

Metoclopramide can be taken with NSAIDs or triptans, and combination products are available in some countries. The typical dose is 10 mg, taken at the start of the attack along with your pain medication.

When Should You Consider Preventive Migraine Medication?

Preventive medication is recommended when you have 3 or more migraine attacks per month, when attacks significantly impair quality of life despite acute treatment, when acute medications are ineffective or contraindicated, or when you risk medication-overuse headache. Options include beta-blockers, antidepressants, anticonvulsants, and CGRP inhibitors.

While acute medications treat individual attacks, preventive (prophylactic) medications are taken daily or regularly to reduce the frequency and severity of migraine attacks. The goal of preventive treatment is typically to reduce migraine frequency by at least 50%, decrease attack severity, improve response to acute treatment, and enhance overall quality of life.

The decision to start preventive treatment should be individualized, considering the frequency and severity of attacks, the impact on daily life and work, response and tolerance to acute treatments, patient preferences, and any comorbid conditions that might favor certain preventive options.

Beta-Blockers

Beta-blockers are among the most well-established preventive medications for migraine. Metoprolol (50-200 mg daily) and propranolol (40-240 mg daily) have the strongest evidence. The exact mechanism in migraine prevention is not fully understood but may involve modulation of the central nervous system's serotonergic pathways and effects on cerebral blood vessels.

Beta-blockers are particularly suitable for patients who also have hypertension, anxiety, or certain cardiac conditions. They should be introduced gradually and doses increased slowly to minimize side effects. When discontinuing, the dose should also be tapered gradually to avoid rebound effects on heart rate and blood pressure.

Common side effects include fatigue, dizziness, cold extremities, and exercise intolerance. Beta-blockers may not be suitable for patients with asthma, as they can affect the airways. Some beta-blockers can cause vivid dreams or nightmares.

Amitriptyline and Other Antidepressants

Amitriptyline is a tricyclic antidepressant that is effective for migraine prevention at doses (10-75 mg daily) lower than those used for depression. It works through multiple mechanisms including inhibition of serotonin and norepinephrine reuptake and effects on pain pathways. It is particularly useful when migraine coexists with tension-type headache, chronic pain conditions, or sleep difficulties.

Amitriptyline should be taken in the evening as it can cause drowsiness. This sedating effect can be beneficial for patients with sleep problems but may be problematic for those who need to be alert in the morning. Other side effects include dry mouth, constipation, weight gain, and cardiac effects at higher doses.

Alcohol can enhance the sedative effects of amitriptyline and should be used cautiously. When starting or stopping treatment, doses should be adjusted gradually.

Angiotensin Receptor Blockers

Candesartan (8-16 mg daily) has shown effectiveness in migraine prevention and may be a good choice for patients who also have hypertension. The mechanism in migraine is not fully understood. It is generally well-tolerated, with the main side effects being dizziness and low blood pressure, particularly at the start of treatment.

Angiotensin receptor blockers are contraindicated in pregnancy as they can cause fetal harm.

Anticonvulsants

Topiramate (25-100 mg daily) reduces neuronal hyperexcitability and has good evidence for migraine prevention. It may be particularly suitable for patients who are overweight, as weight loss is a common side effect. However, it can cause cognitive side effects including word-finding difficulties and concentration problems, which limit its use in some patients.

Valproate is another anticonvulsant with proven efficacy but has significant concerns including weight gain, hair loss, and serious risks in women of childbearing potential (birth defects). It is generally reserved for cases where other options have failed.

Botulinum Toxin (Botox)

For patients with chronic migraine (headache on 15 or more days per month, with migraine features on at least 8 days) who have not responded to other preventive treatments, botulinum toxin injections can be effective. Treatment involves multiple injections around the head and neck, repeated every 12 weeks. The mechanism likely involves reducing sensitization of peripheral nerve endings.

How Do CGRP Inhibitors Work for Migraine?

CGRP (calcitonin gene-related peptide) inhibitors block the action of CGRP, a key molecule in migraine pathophysiology. Monthly or quarterly injections of monoclonal antibodies (erenumab, fremanezumab, galcanezumab) or oral gepants (rimegepant, atogepant) can reduce migraine frequency by 50% or more in many patients, with fewer side effects than traditional preventives.

CGRP is a neuropeptide that plays a central role in migraine. During a migraine attack, CGRP is released from trigeminal nerve endings and causes vasodilation, promotes neurogenic inflammation, and transmits pain signals. Blocking CGRP or its receptor interrupts this cascade and can both treat acute attacks and prevent future ones.

CGRP-targeted therapies represent the first medications specifically developed for migraine based on understanding of migraine pathophysiology. They have transformed migraine treatment for many patients who had limited options previously.

CGRP Monoclonal Antibodies

These are large molecules given by injection that block either CGRP itself or its receptor:

• Erenumab targets the CGRP receptor. Given as a monthly subcutaneous injection (70 mg or 140 mg).
• Fremanezumab targets CGRP directly. Can be given monthly (225 mg) or quarterly (675 mg).
• Galcanezumab targets CGRP. Given as a monthly injection (120 mg after a loading dose).

Clinical trials show that approximately 50% of patients experience at least 50% reduction in monthly migraine days, with some patients achieving even greater benefit. The medications are generally well-tolerated, with the most common side effects being injection site reactions and constipation. They do not cause the sedation, cognitive effects, or weight gain associated with some traditional preventives.

Patients who have not responded adequately to 2-3 previous preventive medications are typically good candidates for CGRP monoclonal antibodies. Response is usually assessed after 3 months of treatment.

Oral CGRP Receptor Antagonists (Gepants)

Gepants are small molecule CGRP receptor antagonists that can be taken orally. They can be used for both acute treatment and prevention:

• Rimegepant can be used for acute treatment (75 mg as needed) and for prevention (75 mg every other day).
• Ubrogepant is approved for acute treatment (50-100 mg).
• Atogepant is used for prevention (30-60 mg daily).

Unlike triptans, gepants do not cause vasoconstriction and may be options for patients with cardiovascular disease who cannot use triptans.

Can Taking Too Much Migraine Medication Cause More Headaches?

Yes, medication-overuse headache (MOH) occurs when acute migraine medications are used too frequently. The risk threshold is approximately 10 days per month for triptans and opioids, and 15 days per month for simple analgesics. Treatment involves withdrawing the overused medication and establishing appropriate preventive treatment.

Medication-overuse headache (previously called rebound headache or drug-induced headache) is a common and important problem. It occurs when the regular use of acute headache medications paradoxically leads to more frequent headaches, creating a cycle where the patient takes more medication, which worsens the problem.

The exact mechanism is not fully understood but involves changes in pain processing pathways and sensitization of the central nervous system. Virtually any acute headache medication can cause MOH if used frequently enough, though the risk varies by medication type.

Risk Thresholds by Medication Type

• Triptans: Risk increases with use on 10 or more days per month
• Simple analgesics (paracetamol, NSAIDs): Risk increases with use on 15 or more days per month
• Opioids: Risk increases with use on 10 or more days per month (opioids are generally not recommended for migraine)
• Combination analgesics: Risk increases with use on 10 or more days per month

Treatment of MOH involves stopping or significantly reducing the overused medication, which typically causes a temporary worsening of headaches before improvement occurs. This withdrawal period can be managed with appropriate support, including bridging treatments, and the establishment of effective preventive therapy to reduce the need for acute medications.

What Medications Are Safe for Children and Adolescents with Migraine?

For children, first-line acute treatments include ibuprofen and paracetamol. Triptans are limited to nasal spray formulations (sumatriptan, zolmitriptan) for adolescents. Children should take medication early in the attack, and preventive treatment may be considered if attacks occur three or more times per month.

Migraine in children and adolescents requires careful consideration of age-appropriate medications. Many medications used in adults have not been extensively studied in pediatric populations, and the risk-benefit profile may differ.

For acute treatment in children, ibuprofen (7.5-10 mg/kg) and paracetamol (15 mg/kg) are first-line options. Children over 7 years may use aspirin, but it should be avoided if fever is present due to the risk of Reye's syndrome. Triptans in nasal spray form (sumatriptan nasal spray, zolmitriptan nasal spray) are approved for adolescents and may be considered when analgesics are insufficient.

It is particularly important in children to take medication early in the attack, as pediatric migraines often have a rapid onset and shorter duration than adult attacks. Waiting too long significantly reduces treatment effectiveness.

The same principles regarding medication overuse apply to children, and parents should be aware that frequent use of acute medications can lead to increased headache frequency.

Preventive treatment in children may be considered when attacks are frequent or significantly impact school attendance and quality of life. Non-pharmacological approaches including sleep hygiene, regular meals, adequate hydration, and stress management should always be part of the treatment plan.

What About Migraine Medication During Pregnancy and Breastfeeding?

During pregnancy, paracetamol is the preferred acute treatment. NSAIDs should be avoided, especially in the third trimester. Triptans require discussion with a healthcare provider. For breastfeeding, most medications pass into breast milk but many are considered compatible with breastfeeding at normal doses.

Migraine management during pregnancy and breastfeeding requires balancing the need for symptom relief against potential risks to the fetus or nursing infant. Many women experience improvement in their migraines during pregnancy, particularly in the second and third trimesters, but others continue to have significant attacks.

Paracetamol (acetaminophen) is considered the safest acute treatment option during pregnancy when used at recommended doses. NSAIDs should be avoided throughout pregnancy where possible, but are contraindicated in the third trimester due to risks including premature closure of the ductus arteriosus and reduced amniotic fluid.

Triptans: While not contraindicated, the safety data for triptans in pregnancy is limited. Sumatriptan has the most data and does not appear to be associated with increased birth defect risk, but decisions should be made in consultation with a healthcare provider weighing individual circumstances.

During breastfeeding, most migraine medications pass into breast milk to some degree. Paracetamol and most NSAIDs are considered compatible with breastfeeding. For triptans, sumatriptan has the most data supporting its safety, particularly if breastfeeding is avoided for a few hours after the dose.

Preventive medications during pregnancy and breastfeeding require careful individual assessment. Many preventive medications are contraindicated or not recommended in pregnancy. Women who require ongoing prevention should discuss options with their healthcare provider before becoming pregnant if possible.

Can Migraine Medications Affect My Ability to Drive?

Some migraine medications can cause drowsiness, dizziness, or visual disturbances that may impair driving ability. Additionally, the migraine attack itself often affects cognitive function and visual perception. Patients should assess their own ability to drive safely before getting behind the wheel.

Both the migraine attack itself and some medications used to treat it can affect driving ability. During a migraine attack, visual disturbances, difficulty concentrating, and sensitivity to light can make driving hazardous even without medication.

Certain medications, particularly those with sedating properties such as some antiemetics and combinations containing codeine, can significantly impair reaction time and judgment. Beta-blockers can cause fatigue, and anticonvulsants like topiramate can affect cognitive function.

Patients are personally responsible for assessing their fitness to drive. If you feel drowsy, dizzy, or your vision is affected, you should not drive. This applies regardless of whether the impairment is from the migraine itself or from medication.