headache+migraine

• Headache


  One of the most common medical complaints reported worldwide

  
• Migraine


  A common primary headache disorder affecting >1 billion people in the world and was the 2nd leading cause of years of living with disability (YDLs) in 2016

  
• Prevalence of migraine and tension-type headache (TTH) is highest in both gender between 18 – 44 years and is inversely related to income and educational attainment

  
• Main primary headache disorders

  • Migraine
  • Tension-type headache (TTH)
  • Cluster headache

  
• Migraine headache


  • Characterized by attacks of severe, often unilateral, pulsating, throbbing in nature that increase in intensity with physical activity
  • Accompanied by loss of appetite, nausea, vomiting, photophobia, sensitivity to noise and hypersensitivity to certain smells
  • Signs of parasympathetic activation, eye tearing commonly found in 82% of patients
  • May change side during and attack or from one attack to another attack
  • Duration: Between 4 and 72 hours if untreated

  
• Migraine without aura


  At least 5 attacks, headache lasts 4-72 hours, has at least 2 of the following characteristics: unilateral location, pulsating quality, moderate or severe intensity, aggravation by or avoidance of routine physical activity, and during headache at least 1 of the following: nausea, photophobia & phonophobia, not attributed to another disorder

  
• Migraine with aura (classic migraine)

  At least 2 attacks, fulfills criteria for typical aura, hemiplegic migraine, retinal migraine or brainstem aura, not attributed to another disorder

  
• Typical aura


  Fully reversible visual, sensory or speech symptoms but no motor weakness, bilateral visual symptoms (+ve features: flickering lights, spots, lines OR -ve features: loss of vision), unilateral sensory symptoms (+ve features: pins and needle, -ve features: numbness), at least 2 of the following: ≥ 1 symptoms developed over 5 min OR different symptoms that occur in succession OR both, each lasts at least 5min but no longer than 60mins, experience migraine with aura following with aura within 60mins
• Goals of treatment


  • To treat migraine attacks rapidly and consistently without recurrence
  • To restore the patient's ability to function
  • To minimize the use of backup and rescue medications
  • To educate and enable patients to manage their disease
  • Be cost-effective in overall management
  • To prevent or minimize adverse effects
• Non-pharmacological management


  • Apply ice to the head
  • Recommend periods of rest or sleep in a dark, quiet environment
  • Identify and avoid triggers of migraine attacks
  • Behavioral intervention therapy such as relaxation therapy, biofeedback and cognitive therapy
• Commonly reported triggering factors

  • Food: alcohol, caffeine / caffeine withdrawal, chocolate, fermented or pickled foods, MSG, saccharin / Aspartame
  • Environmental: glare / flickering lights, high altitude, loud noises, strong smells / fumes, tobacco smoke, weather changes
  • Behavioral-Psychologic triggers: excess or lack of sleep, fatigue, menstruation, menopause, skipped meals, strenuous physical activity, stress or post stress
• Pharmacological management


  • Analgesics and NSAIDs
  • Antiemetics
  • Ergot Alkaloids and Derivatives
  • Serotonin Receptor Agonists
  • Opiate Analgesics
• Analgesics and NSAIDs


  Simple analgesics and NSAIDs are first line treatment for mild to moderate migraine attacks or severe attacks that are responsive in the past, NSAIDs appear to prevent neurogenically mediated inflammation in the trigeminovascular system by inhibiting prostaglandin synthesis, long half-life NSAIDs preferred, metoclopramide may enhance absorption of analgesic and alleviate migraine-related nausea & vomiting, drawbacks: NSAIDs associated with GIT and CNS side effects
• Analgesics and NSAIDs


  • Paracetamol, Aspirin, Ibuprofen, Naproxen, Diclofenac
• Ergot Alkaloids and Derivatives


  Useful for moderate to severe migraine attacks, non-selective 5HT1 receptor agonists → constrict intracranial blood vessels and inhibit development of neurogenic inflammation in the trigeminovascular system, common side effects: nausea & vomiting, contraindicated in renal and hepatic failure, coronary, cerebral or peripheral vascular disease, uncontrolled HTN, sepsis, pregnant and nursing patient
• Ergot Alkaloids and Derivatives


  • Ergotamine tartrate, Dihydroergotamine
• Serotonin Receptor Antagonists (Triptans)

  First-line therapy for mild to severe migraine and be used for rescue therapy when non-specific medications are ineffective, they are selective 5HT1B and 5HT1D receptors agonists relieving migraine by: 1) Normalization of dilated arteries, 2) Inhibition of vasoactive peptide release, 3) Inhibition of transmission via second-order neurons ascending to the thalamus, common side effects: paresthesias, fatigue, dizziness, flushing, warm sensations and somnolence, contraindicated in patients with h/o IHD, uncontrolled hypertension, cerebrovascular disease
• Serotonin Receptor Antagonists (Triptans)


  • Sumatriptan, Eletriptan, Naratriptan, Rizatriptan, Zolmitriptan
• Anti-emetics


  Use as adjunctive therapy to combat nausea & vomiting from the headache and side effects of Ergotamine derivatives, may consider as pre-treatment → administer 15-30 min prior to oral abortive medications, medications: PO Metoclopramide, chlorpomazine or prochlorperazine, supp preparations are available when nausea & vomiting are prominent
• Anti-emetics


  • Metoclopramide, Prochlorperazine
• Opiate Analgesics


  Only reserved for moderate to severe infrequent headaches in whom conventional therapies are contraindicated or have failed, controversial because can cause central sensitization, have no vasopressor or anti-inflammatory effects, increase risk of medication-overuse headache, must be supervised closely → risk of sedation and drug abuse
• Opiate Analgesics


  • Meperidine, butorphanol, oxycodone, hydromorphone
• Pharmacologic Prophylaxis of Migraine


  Administered daily to reduce the frequency, severity and duration of attacks, and to increase responsiveness to acute therapies, consider prophylaxis in the setting of recurring migraines produce significant disabilities, drug selection is based on side effect profiles and comorbid conditions → similar efficacy, initiate with low dose and titrate gradually until therapeutic effects achieved or side effects become intolerable, continue treatment for at least 6-12 months after episodes diminished, then gradual tapering and discontinue
• Criteria for prophylaxis treatment

  • Headache recur in a predictable manner (menstrual migraine)
  • NSAID or triptan at the time of vulnerability
  • Healthy or comorbid hypertension or angina

  
• Prophylactic medications


  • Beta-Blockers (Verapamil if contraindicated or ineffective)
  • Antidepressants
  • Anticonvulsants
  • Botulinum toxin
• β – Blockers


  Raise the migraine threshold by modulating adrenergic or serotogenic neurotransmission in cortical or subcortical pathways

  
• β – Blockers


  • Propranolol, timolol and metoprolol reduce 50% frequency of migraine attacks in 50% of patients (RCTs)
  • Atenolol and Nadolol are probably effective, while nebivolol and pindolol are possibly effective
  • May be useful in patients with comorbid hypertension or angina
  • Bronchoconstrictive and hyperglycemic effects can be minimized with β1-selective blockers
• Antidepressants


  Related to downregulation of central 5-HT2 receptors, increased level of synaptic norepinephrine and enhanced endogenous opioid receptor actions
• Antidepressants


  • Amitriptyline (TCA) and Venlafaxine (SNRI) are probably effective for migraine prophylaxis
  • There are insufficient data to support the efficacy of other anti-depressants
• Amitriptyline


  • Anticholinergic side effects, hence limit its use in patients with BPH and glaucoma
  • Prefer evening dose due to sedation effect
  • May cause increased in appetite and weight gain
  • Orthostatic hypotension and cardiac toxicity also are reported occasionally
• Venlafaxine


  • Nausea, vomiting and drowsiness
  • Potential risk of serotonin syndrome if use with triptan
• Anticonvulsants


  • Valproic acid, divalproex sodium and topiramate can reduce frequency, severity and duration of headaches
  • Enhancement of GABA-mediated inhibition
  • Modulation of excitatory neurotransmitter glutamate
  • Inhibition of sodium and calcium ion channel activity
• Valproic acid & Divalproex sodium


  • Side effects: Nausea & vomiting (less in divalproex), alopecia, tremor, asthenia, somnolence and weight gain
  • Hepatotoxicity is a serious SE but the risk is low in monotherapy with no underlying metabolic or neurologic disorder
  • Divalproex is in ER formulation →More tolerated (OD dosing)
  • Valproate is contraindicated in pregnancy, patients with h/o pancreatitis and chronic liver diseases
• Topiramate


  • Should be initiated at low dose and titrate upward
  • Approx 50% patients respond to it
  • Adverse events: Paresthesia (most common), fatigue, anorexia, diarrhea, weight loss, hypesthesia
  • Should be used in caution / avoided in patients with h/o kidney stones or cognitive impairment
• Non-Steroidal Anti-Inflammatory Drugs


  • Modestly effective to reduce frequency, severity and duration of migraine attacks
  • Limited for daily or prolonged use → GIT and renal toxicity
  • Has been used intermittently to prevent headaches that recur in a predictable manner e.g. menstrual migraine
  • Treatment should be initiated up to 1 week prior to expected headache onset and continued for no more than 10 days
  • Monitor RFT and occult blood loss if long-term therapy is needed
  • Naproxen has the strongest efficacy but aspirin the weakest
• The most common type of primary headache, more common in women than men and the incidences decreases with age

  
• Pain is usually mild to moderate and non-pulsatile
• 64% experienced infrequent episodic TTH (<1 episodes/month), 22% had frequent TTH (1-14 episodes/month)
• Risk associated with a poor outcome in tension-type headache (TTH)


  • Coexisting migraine
  • Sleep problems
  • Anxiety
  • Poor stress management
  • Presence of chronic TTH
• Pathophysiology of Tension-Type Headache


  Mental stress, non-physiologic motor stress, a local of myofascial release of irritants or a combination of these may be initiating stimulus