Migraine: Drug Therapy

Therapy goals

  • Avoidance of migraine attacks
  • Improvement of the symptomatology in existing migraine attack.

Therapy of acute migraine

Therapy recommendations

  • General points for attention:
    • Drug therapy should be started as early as possible.
    • In migraine with aura, analgesics (painkillers) can be taken at the onset of aura. Sufficient dosage (starting dose) must be taken from the beginning. Notice: During migraine attacks, absorption of analgesics is delayed, possibly due to impaired gastrointestinal motility during the migraine attack. A combination of analgesics with prokinetic (motility-enhancing) effective antiemetics (antinausea drugs) is therefore indicated.
      • Before analgesic administration, nausea/nausea should be treated initially with, for example, domperidone (dopamine antagonist), because the frequent vomiting of patients would make the analgesic insufficient.
      • Approximately 10 minutes after application of the antiemetic (e.g., tablets, drops; in case of severe nausea and/or vomiting: suppository or parenteral application), the analgesic can be administered: Paracetamol (first-line agent: children, pregnant women and nursing mothers) or ibuprofenIbuprofen showed the best tolerability in a network analysis of 88 studies.
  • Acute therapy
    • Mild to moderate migraine: analgesics (acetylsalicylic acid (ASA 1,000 mg) and other nonsteroidal anti-inflammatory drugs (NSAIDs; diclofenac, ibuprofen) or the pyrazolone derivative metamizole); for contraindications to NSAIDs, acetaminophenIbuprofen showed the best tolerability in a network analysis of 88 studies.
    • Severe migraine: triptans (serotonin receptor agonists); indications: severe migraine attacks in which nonspecific analgesics or the combination of antiemetic and analgesic are not sufficiently effective.The triptan can be given together with a long-acting analgesic, this combination is superior to the respective monotherapy. Notice:
      • They should be taken as early as possible in the headache phase of migraine. They are not effective in the aura phase of migraine!
      • For triptans, the threshold for a drug-induced headache (medication-overuse headache) is ≥ 10 days of intake per month, over a period of at least 3 months.

    Eletriptan (drug from the triptans group) showed the best efficacy in a network analysis of 88 studies.Interactions: Cotherapy of triptans with SSR or SNRI should actually be avoided because of the risk of serotonin syndrome (serotonergic syndrome); however, this is not necessary: according to registry data, a serotonin syndrome is detected in less than ten out of 100,000 patients per year when taken concomitantly.

  • Medical emergency and acute treatment of migraine: lysine acetylsalicylate 1,000 mg i. v.; metamizole; sumatriptan 6 mg s. c.; metoclopramide 10 mg i. v.; glucocorticoids).
  • Status migraenosus: glucocorticoids (dexamethasone or prednisolone).
  • Prophylaxis of migraine: beta blockers (metoprolol, propranolol); calcium antagonist (flunarizine); anticonvulsants (topiramate, valproic acid); tricyclic antidepressant amitriptyline; monoclonal antibodies (erenumab, fremanezumab, galcanezumab).
  • Chronic migraine: topiramate and onabotulinumtoxin A.
  • For therapy of menstrual migraine (migraine without aura, whose attacks occur in at least two of three cycles in the days around menstruation (menstrual period); frequency: about 10-15% of women) see under premenstrual syndrome (PMS)Note: Acute treatment of menstrually timed migraine is not fundamentally different from that of nonmenstrual attacks

Note

  • The following thresholds apply to the development of drug-induced headache (drug-induced headache):
    • Use of monoanalgesics for more than 15 days/month.
    • Taking combination analgesics on more than 10 days/month
    • Taking combinations of different analgesics on more than 10 days/month

Prophylaxis of migraine

Indications for migraine prophylaxis are:

  • Migraine attacks lasting regularly > 72 h.
  • ≥ 3 severely debilitating migraine attacks per month; ≥ 6 migraine days/month requiring treatment.
  • Complicated migraine attacks with debilitating and/or long-lasting auras.
  • Condition following migrainous infarction when other causes of infarction have been excluded.
  • There are neurological symptoms during the attack
  • A strong suffering pressure is present
  • Taking analgesics or migraine medications for > 10 days per month.
  • The acute therapy is not tolerated
  • Therapy-resistant migraine attacks are present; inadequate attack therapy (lack of efficacy, safety or tolerability).
  • Recurrent status migraenosus
  • Contraindications to triptans and/or intolerable side effects of acute therapy.

Drug prophylaxis of migraine

  • First-line agent:
  • Second-line agent:
    • Topiramate* (antiepileptic) [for epilepsy patients with comorbid migraine and for patients with chronic migraine] (USA: esp. in children and adolescents).
    • Flunarizine (calcium antagonists).
    • Valproate (antiepileptic drug) [for epilepsy patients with comorbid migraine; for women of childbearing age, ensure safe contraception!].
  • Third-line agent:
  • Other remedies:
    • Monoclonal antibodies: erenumab – when other drug therapy has been exhausted and there are at least four migraine days per month.
    • Onabotulinumtoxin A – is also recommended for prophylaxis of chronic migraine.
  • Eachte: Prophylaxis is considered effective if the frequency of attacks has decreased by at least 50% after approximately 2 months after reaching the maximum tolerated dose
  • An assessment of the efficacy of oral migraine prophylaxis should generally be made no earlier than 8 weeks after the target dose has been reached, although some improvement may occur in the first month of treatment.
  • The duration of effective drug prophylaxis should be at least 6 – 12 months.
  • See also under “Further therapy”.

* In children and adolescents, only topiramate showed a significant effect in the prophylaxis of migraine in a meta-analysis. Further references

  • Monoclonal antibodies
    • Compared with placebo, erenumab (monoclonal antibody) statistically significantly reduced mean migraine days by 1.4-1.9 days per month in episodic migraine and by 2.5 days per month in chronic migraine.
    • Compared with placebo, galcanezumab statistically significantly reduced mean migraine days by 3.7-4 days per month in episodic migraine and by 4.3-4.7 days per month in chronic migraine.
    • The G-BA has decided with regard to erenumab that for patients who do not respond to any of the available therapies (metoprolol, propranolol, flunarizine, topiramate, amitriptyline, valproic acid or Clostridium botulinum toxin type A), do not tolerate them or these therapies are not suitable for them, there is evidence of substantial additional benefit.
  • A randomized double-blind trial of migraine headache treatment in children and adolescents demonstrated that placebos were as effective for prophylaxis as otherwise prescribed medications (amitriptyline: 1 mg/kg/die or topiramate: 2 mg/kg/die). Placebos also had significantly better tolerability.
  • Taking valproic acid during pregnancy harms the child’s intelligence in the long term.
  • Pregabalin was significantly superior to propranolol in reducing the number and duration of monthly migraine attacks in children
  • Red-hand letter (AkdÄ Drug Safety Mail): contraindications, warnings, and measures to avoid exposure to valproate during pregnancy:
    • In girls and women of childbearing age, valproate should be used only if other treatments are not effective or are not tolerated.
    • Valproate is contraindicated in women of childbearing age unless the pregnancy prevention program is followed.
    • Valproate is contraindicated in epilepsy during pregnancy unless no suitable alternatives are available.
    • Valproate is contraindicated during pregnancy for bipolar disorder and migraine prophylaxis.

Micronutrients

Active ingredient group Active ingredients Dosage Special features
Vitamins Vitamin B2 400 mg/d
Minerals Magnesium 600 mg/d For acute migraine painalso suitable for prophylaxis in children
Other micronutrients Coenzyme Q10 see below Therapy with micronutrients

Drug prophylaxis of chronic migraine

  • Topiramate (50-100 mg/d)
  • Botulinum toxin A (botulinum neurotoxin A; BoNT-A)/onabotulinum toxin A.
  • Indication: chronic migraine
  • Contraindications: Myasthenia gravis; side effects: Facial asymmetries, allergic reaction, hematomas (bruises), inflammation.
  • Dosage: 155-195 units; distributed over 31-39 injection sites.
    • Year 1: adherence to 3-month intervals is reasonable in year 1.
    • 2nd year: after successful treatment in the 1st year, without regular significant deterioration towards the end of the 3-month intervals → extend treatment interval to 4 months; after successful extension of the interval to 4 months and stable improvement over at least two consecutive 4-month intervals → omission attempt can be made.
  • Meta-analysis confirms limited efficacy of Botox treatment: slight decrease in headache days of 1.56 episodes per month (benefit was statistically significant with a 95% confidence interval of 0.07 to 3.05 fewer episodes per month).

Drug prophylaxis of menstrual migraine

Drug prophylaxis of migraine in pregnancy and lactation

Phytotherapeutics

  • Butterbur for migraine prophylaxis in adults and children.

Supplements (dietary supplements; vital substances)

Suitable dietary supplements should contain the following vital substances:

Note: The listed vital substances are not a substitute for drug therapy. Food supplements are intended to supplement the general diet in the particular life situation.