What are suitable migraine preventative medications for a 28-year-old with no underlying medical problems aside from migraines?

Migraine Preventive Medications for a 28-Year-Old

Start with propranolol (80-240 mg/day), timolol (20-30 mg/day), topiramate (100 mg/day), or candesartan as first-line preventive therapy for this young, otherwise healthy patient with migraines. 1

When to Initiate Preventive Therapy

You should start preventive medication if this patient experiences any of the following 1:

• Two or more migraine attacks per month with disability lasting 3 or more days per month
• Using abortive medications more than twice per week (risk of medication overuse headache)
• Contraindications to or failure of acute treatments
• Uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction)

First-Line Medication Options

Beta-Blockers

• Propranolol (80-240 mg/day) or timolol (20-30 mg/day) have the strongest evidence for efficacy and are FDA-approved for migraine prophylaxis 1, 2
• Alternative beta-blockers include atenolol, bisoprolol, or metoprolol if propranolol is not tolerated 1
• These are particularly useful if the patient has comorbid hypertension 1, 2

Topiramate

• Target dose is 100 mg/day (typically 50 mg twice daily) with strong evidence supporting efficacy 1, 2
• No additional benefit seen at 200 mg/day compared to 100 mg/day 3
• Especially preferred for patients concerned about weight gain or who are currently overweight, as it causes weight loss rather than gain 3, 4
• Start at 25 mg daily and increase by 25 mg every 10 days to minimize side effects 5, 6
• Most common adverse events are paresthesia (48%), weight loss (50%), fatigue, decreased appetite, and cognitive disturbances (20%) 3, 5, 4
• Paresthesia is common early but rarely causes discontinuation; cognitive problems are less frequent but more troublesome 4
• Extended-release formulations may reduce cognitive side effects compared to immediate-release 4

Candesartan

• Effective first-line agent, particularly useful if hypertension is present 1, 2

Second-Line Options

If first-line treatments fail or are not tolerated 1, 2:

• Amitriptyline (30-150 mg/day) - particularly effective for mixed migraine and tension-type headache 1
• Flunarizine - effective where available 1
• Sodium valproate (800-1500 mg/day) or divalproex sodium (500-1500 mg/day) - STRICTLY CONTRAINDICATED in women of childbearing potential due to teratogenic effects 1, 2, 5

Given this patient is a 28-year-old woman, avoid valproate/divalproex entirely unless she has documented infertility or permanent contraception.

Implementation Strategy

Dosing Approach

• Start with a low dose and titrate slowly to minimize side effects and improve tolerability 1, 2
• Allow an adequate trial period of 2-3 months before determining efficacy 1, 2, 6
• Topiramate may show efficacy as early as the first month, but full evaluation requires 2-3 months 6

Monitoring

• Use headache diaries to track attack frequency, severity, duration, disability, treatment response, and adverse effects 1, 2
• Monitor for medication overuse, which can interfere with preventive treatment 1

Duration of Therapy

• Consider pausing preventive treatment after 6-12 months of successful therapy to determine if it can be discontinued 1
• Calculate percentage reduction in monthly migraine days to quantify success 1

Critical Pitfalls to Avoid

• Do not start with too high a dose - leads to poor tolerability and discontinuation 1
• Do not conclude treatment failure before 2-3 months of adequate dosing 1, 2
• Do not prescribe valproate/divalproex to this 28-year-old woman unless she has documented permanent contraception 1, 2
• Monitor for medication overuse headache from frequent acute medication use (more than twice weekly) 1

Non-Pharmacological Adjuncts

Consider adding 1, 2:

• Neuromodulatory devices
• Biobehavioral therapy
• Acupuncture

These can serve as adjuncts to medication or as stand-alone treatments when medications are contraindicated.

Newer Options for Treatment-Resistant Cases

If first- and second-line options fail 1:

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) should be considered
• Efficacy should be assessed only after 3-6 months of treatment 1