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Migraine preventives : doses, side effects and contra-indications

drawing Risk and reward balance scale on the chalkboard.

Migraine [1] Canada (MC) is a patient association, not a treating health care provider. MC cannot provide medical advice. Nevertheless, the basics of medications are public knowledge and many people ask about this type of medical information. This table is given as a general reference. Any decision to take medication should be discussed with a health care provider. 

Table : Migraine [1] Preventives 

  Usual dose Main side effects [2] Choose for patients with Avoid in patients with
Frequently used 
Amitriptyline
[3]Elavil

Nortriptyline
Aventyl
10 to 50 mg at bedtime Weight gain
Drowsiness
Confusion
Urinary retention
Constipation
Dry mouth, eyes
Blood pressure changes
Insomnia
[4]Other chronic painTension type headache
Note -no benefit for treating depression at lower doses
Obesity
Acute Glaucoma
Prostate disease
Heart block
Bipolar disorder
Elderly
Propranolol
Inderal

Nadolol
Corgard
80 to 160 mg daily or divided twice daily 

Fatigue
Reduced ability to exercise

Weight gain
Low blood pressure/heart rate
Sexual dysfunction
Nightmares

High blood pressure [5]
Anxiety
Essential tremor

Raynaud’s disease
Asthma
Heart block
Low blood pressure

Low heart rate

Candesartan
Atacand
8 to 16 mg daily Low blood pressure
Dizziness [6]
High blood pressure Low blood pressure
Topiramate
[7]Topamax
50 to 200 mg daily or divided twice daily Thinking difficulties
Tingling sensation in limbs
Weight loss
Kidney stones
Anxiety, mania
Visual disturbances
Glaucoma (rare)
Obesity
Epilepsy
Essential tremor
Chronic migraine [8]
Kidney stones
Glaucoma
Use with caution in depression/anxiety
Onabotulinum Toxin Type A
Botox
155 to 195 units injected by physician Local pain after injections
Cosmetic asymmetry in the face (dropped brow etc)
Neck weakness (rare)
Chronic migraine [1] only Neuromuscular disease
Note – blood clotting disorders are not a strict contra-indication.
CGRP monoclonal antibodies (MABs)
Erenumab
(Aimovig)
70 mg or 140 mg every 28 days

Constipation
Skin reaction at the injection site
Pain in muscles and joints
Allergy /hypersensitivity reaction

High blood pressure
** Other reactions not seen in studies but reported in practice: weight gain, hair loss, nightmares, anxiety, increase in headache
Frequent episodic (8-14 days/month) or chronic (15+ days per month) migraine [1] who have failed previous preventive treatments (will not be covered by insurance as first line treatment) Women who want to get pregnant
People with allergy to a CGRP antibody
At risk for constipation (plan for management) Uncontrolled vascular disease
Galcanezumab
(Emgality)
First dose:240 mg then 120 mg every 28 days Skin reaction at the injection site
Pain in muscles and joints
Allergy /hypersensitivity reaction
** Other reactions not seen in studies but reported in practice: weight gain, hair loss, nightmares, anxiety, increase of the headache
Frequent episodic (8-14 days/month) or chronic (15+ days per month) migraine who have failed previous preventive treatments (will not be covered by insurance as first line treatment) Women who want to get pregnant
People with allergy to a CGRP antibody
Uncontrolled vascular disease
Fremanezumab
(Ajovy)
225 mg every 28 days or 675 mg every 3 months Skin reaction at the injection site
Pain in muscles and joints
Allergy /hypersensitivity reaction
** Other reactions not seen in studies but reported in practice: weight gain, hair loss, nightmares, anxiety, increase of the headache
Frequent episodic (8-14 days/month) or chronic (15+ days per month) migraine who have failed previous preventive treatments (will not be covered by insurance as first-line treatment) Women who want to get pregnant
People with an allergy to a CGRP antibody
Uncontrolled vascular disease
Natural products and supplements
Magnesium
[9]citrate or glycinate
300 mg BID Stomach cramps, diarrhea Constipation Loose bowel movements, cramps
Vitamin B2
(riboflavin)
400 mg daily Yellow/orange urine None None
Coenzyme Q10 300 mg (divided once or three times daily) Stomach upset None None
Butterbur
(Petadolex)
75 mg twice daily  (burping) Warning – Some formulations may contain toxic chemicals that can cause liver damage.

Only formulations that have been proven to be safe because these toxic chemicals have been removed should be used (for example Petadolex).
None
Should NOT be first line, less frequently used, low evidence for efficacy but may be used in selected cases with significant comorbidity [10]
Verapamil
Isoptin
240 mg daily Constipation
Leg swelling
Heart block, fatigue
High blood pressure
Angina
Constipation
Low blood pressure
Gabapentin
Neurontin
1200- 2400 daily (divided doses) Drowsiness
Dizziness [6]
Weight gain 
Epilepsy
Nerve pain
Insomnia [4]
Kidney failure (dose adjustment)
Venlafaxine
Effexor
150 -225 mg daily Nausea, vomiting, dry mouth, constipation
Nightmares
Drowsiness
Depression
Anxiety
High blood pressure
Kidney failure
Valproic acid 500 to 1000 mg twice daily Nausea, tremor, weight gain, hair loss, diarrhea, dizziness
[6]Liver toxicity
Parkinsonism
Teratogenicity
Epilepsy
Bipolar disease
Women of childbearing age

 

REFERENCES

  • Pringsheim T, Davenport W, Mackie G, Worthington I, Aube M, Christie SN, et al. Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci. 2012;39(2 Suppl 2):S1-59.
  • Rajapakse T, Pringsheim T. Nutraceuticals in Migraine: A Summary of Existing Guidelines for Use. Headache. 2016;56(4):808-16.
  • Tepper SJ. History and Review of anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: From Translational Research to Treatment. Headache. 2018;58 Suppl 3:238-75.
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