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Pharmacotherapy of migraine

INTRODUCTION

Headache simply means pain in the head. The pain comes from pain-sensitive structures of the head.

Headache disorders are classified into primary and secondary.

Primary headaches are characterised by lack of an identifiable and treatable underlying cause. Examples: Tension, Migraine and Cluster headache.

Secondary headaches are characterised by an identifiable and treatable underlying cause. Causes include vascular disorders; trauma; metabolic disorders; substances or their withdrawal etc.

Migraine headache

Migraine is defined as a recurrent headache disorder manifesting in attacks lasting 4 to 72hrs (ICHD, 2013).

It has two major subtypes: migraine with aura (or classical migraine)  and migraine without aura (or common migraine).

Prevalence varies with age and gender. Before age 12, prevalence is higher in males than in females. But after age 12, prevalence is 2-3 times more in females than males (ICHS, 2013). Migraine is the 3rd most prevalent disorder and 7th highest specific cause of disability world wide (GBD, 2010).

Migraine Prevalence
               Age and Gender

SYMPTOMS OF MIGRAINE HEADACHE

Common symptoms include:

Unilateral location

Pulsating quality

Moderate or severe pain intensity

Worsen by routine physical activity.

Associating symptoms include:

Nausea

Vomiting

Photophobia

Phonophobia

POSSIBLE TRIGGERS OF MIGRAINE ATTACK

  • Foods containing tyramine
  • Bright lights/glare
  • Smells/odours
  • Dieting/hunger
  • Loud noise/sound
  • Changes in altitude
  • Stress
  • Weather changes
  • Caffeine
  • Alcoholic beverages
  • Changes in sleep habits
  • Hormonal fluctuations/ menstrual cycle

Phases of a Migraine Attack

PATHOPHYSIOLOGY OF MIGRAINE

Vascular theory: Postulates that migraine headache is due to alteration in the diameter of cranial blood vessels.

Neurovascular theory: Postulates that migraine headache is due to dysfunction of the trigeminovascular system.

Disturbances in 5-HT activities: Disturbances in 5-HT activities is believed to be an important mediator of migraine headache.

DIAGNOSIS OF MIGRAINE

Consider the following for initial assessment;

Age of patient

Gender

Headache

Site

Associating symptoms

Evolution and resolution

Periodicity

Precipitating factors.

DIAGNOSTIC CRITERIA ( ICHD, 2013)

Migraine with aura

A. At least 2 attacks fulfilling criteria B and C

B. One or more of the following fully reversible aura symptoms: Visual, Sensory, Speech and/or language, Motor, Brainstem, Retinal.

C. At least two of the following four characteristics:

  • At least one aura symptom spreads gradually over 5 minutes, and/or two or more symptoms occur in succession.
  • Each individual aura symptoms lasts 5-60 minutes.
  • At least one aura symptom is unilateral.
  • The aura is accompanied or followed within 60 minutes by headache.

Migraine without aura

A. At least 5 attacks fulfilling criteria B-D

B. Headache attacks lasting 4-72hrs (untreated or unsuccessfully treated).

C. Headache has 2 or more of the following characteristics:

  • unilateral location
  • Pulsating quality
  • moderate or severe pain intensity
  • Aggravation by or causing avoidance of routine physical activity (e.g. walking or climbing stairs).

D. During headache at least one of the following:

  • Nausea and /or vomitting
  • Photophobia and /or Phonophobia

TREATMENT OF MIGRAINE

MODALITIES:

  1. Drug therapy (Pharmacotherapy)
  • Acute (abortive or symptomatic) treatment.
  • Long-term (preventive or prophylactic) treatment.
  1. Non  Drug Therapy.

Acute and prophylactic therapy:

Drugs used for acute therapy.

Migraine specific drugs

  • Ergot alkaloids and derivatives
  • Triptans

Migraine non-specific drugs.

  • Analgesics (opioid and non-opioid analgesics)
  • Anti emetics
  • corticosteroids

A. MIGRAINE SPECIFIC DRUGS

ERGOT ALKALOIDS AND DERIVATIVES:

Include Ergotamine and Dihydroergotamine (DHE)

Were once the mainstay before the triptans were developed

Are non- selective 5-HT1 receptor agonist causing constriction of intracranial blood vessels and inhibition of development of neurogenic inflammation  in the trigeminovascular system.

Side effects include nausea, vomiting, abdominal pain, fatigue, diarrhoea, muscle pain, etc.

TRIPTANS

They are divided into:

—1st generation ( sumatriptan)

—2nd generation ( almo-, trova-, nara-, riza- and zolmi- triptans).

2nd  generation triptans have improved bioavailability.

Are the most effective antimigraine drugs.

They act by reducing the excitability of neurons in the trigeminovascular system via stimulation of brainstem 5-HT1B/1D receptors.

b. MIGRAINE NON-SPECIFIC DRUGS

Opioid analgesics

Include Meperidine, Butorphanol, Hydromorphone and oxycodone.

Can produce tolerance and physical dependence

Reserved for patients with:

  • Moderate-severe infrequent pain
  • Conventional therapies are contraindicated
  • Conventional therapies have failed

Non opioid analgesics

E.g. Acetaminophen, acetyl salicylic acid, and NSAIDS are usually used as first line treatment options for mild to moderate pain attack.

More effective when:

—Initiated early

— Pain is mild

— In the absence of Nausea disability.

They do not produce tolerance and physical dependence.

Anti emetics

E.g. Metoclopramide, Domperidone, Phenothiazines and Antihistamines.

  • Can be given orally, intra-muscularly or rectally.
  • Have added advantage of promoting gastric emptying and normal peristalsis.
  • Phenothiazines can reduce GI motility and further impair absorption of medications orally.

PROPHYLACTIC TREATMENT

CRITERIA FOR CONSIDERING PROPHYLAXIS

Headaches occurring so frequently that acute medications are overused.

Disabling headaches that are unresponsive to abortive treatments.

Patients in whom acute drugs are contraindicated.

Headaches that present a significant risk for future morbidity and mortality.

GOALS

To reduce the frequency of attacks, severity and duration of migraine.

To increase the effectiveness of acute therapy.

To avoid medication over use headache (MOH).

DRUG OPTIONS

  • Antihypertensives e.g. Propranolol and Calcium channel blockers.
  • Antidepressants e.g. Amitriptylline and Nortriptylline.
  • Anticonvulsants e.g. Valproate and Topiramate
  • Ergot alkaloids e.g. Methysergide

Propranolol, Amitriptylline and Valproate are first line agents.

Methysergide are reserved for patients with refractory headaches that do not respond to other preventive therapies.

NON-DRUG THERAPY

Regular sleep-pattern

Eating habit

Smoking cessation

Limited caffeine intake

Relaxation therapy.

Role of pharmacists in management of migraine

Advice, educate and instruct patients in the appropriate use of OTC analgesics in migraine to reduce the risk of medication over use headache.

Selection of appropriate medications for the patients to achieve control of the migraine headache.

Encourage patients on adherence to their medications to achieve optimal outcomes.

Suggest that headache patients keep a “diary” as a record of when their episodes occur.

Pharmacotherapy in Migraine

Conclusion

Migraine significantly affect patient’s lives as they may lead to significant impairment of daily function and quality of life. For best results, acute migraine therapy should be  administered as early as possible when migraine symptoms occur. If migraines are severe and debilitating, occurring frequently, or if acute migraine therapies are ineffective or cannot be used, then preventive therapy should be considered.

Reference

Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders. 2nd edition. Cephalalgia. 2004;24(suppl1):117-118,138.

Cady RK. Diagnosis and treatment of migraine. Clinical Cornerstone. 1999;1(6):21-32.

Wober C et al. J Headache Pain. 2006;7(4):188-195.

Friedman DI and De Ver Dye T. Headache. 2009;49(6):941-952.

Tepper SJ and Spears RC. Neurol Clin. 2009;27(2):417-427.

Silberstein SD. Neurol Clin. 2009;27(2):429-443.

Goldberg LD. The cost of migraine and its treatment. Am y manage care.2005;11:S62-S67.

http://www. Migraine mentors.com/employees/common medications.asp. Assessed online on 01/08/16

Hauwa  Ahmed (B. Pharm)

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