Preventive drugs are used to reduce the frequency, duration, and severity of migraine attacks. Because of frequent unpleasant and sometimes debilitating side effects, preventive drugs are only prescribed for those migraineurs whose quality of life is significantly adversely affected. The most commonly prescribed drugs for migraine prevention are beta-blockers, antidepressants, and anticonvulsants. The drugs are started at a low dose, which is gradually increased until therapeutic effects develop, the ceiling dose for the chosen drug is reached, or side effects become intolerable.
The beta-blocker, propranalol's effectiveness in headache treatment was a chance finding in patients receiving the drug for angina (chest pain due to a lack of blood to the heart muscle). The beta-blockers that are used in migraine treatment are propranolol, nadolol, timolol, metoprolol, and atenolol.
Adverse drug reactions (ADRs) associated with the use of beta blockers include: nausea, diarrhea, bronchospasm, dyspnea, cold extremities, exacerbation of Raynaud's syndrome, bradycardia, hypotension, heart failure, heart block, fatigue, dizziness, alopecia (hair loss), abnormal vision, hallucinations, insomnia, nightmares, sexual dysfunction, erectile dysfunction and/or alteration of glucose and lipid metabolism. Due to the high penetration across the blood–brain barrier, lipophilic beta blockers, such as propranolol and metoprolol, are more likely than other, less lipophilic, beta blockers to cause sleep disturbances, such as insomnia and vivid dreams and nightmares.
Amitriptyline has been more frequently studied of the antidepressants and is the only antidepressant with fairly consistent support for efficacy in migraine prevention. The method of headache prevention with antidepressants is uncertain, but does not result from treating masked depression.
The main two side effects that occur from taking amitriptyline are drowsiness and a dry mouth. Other common side effects of using amitriptyline are mostly due to its anticholinergic activity, including: weight gain, changes in appetite, muscle stiffness, nausea, constipation, nervousness, dizziness, blurred vision, urinary retention, and changes in sexual function. Some rare side effects include seizures, tinnitus, hypotension, mania, psychosis, sleep paralysis, hypnagogic or hypnopompic hallucinations related to sleep paralysis, heart block, arrhythmias, lip and mouth ulcers, extrapyramidal symptoms, depression, tingling pain or numbness in the feet or hands, yellowing of the eyes or skin, pain or difficulty passing urine, confusion, abnormal production of milk in females, breast enlargement in both males and females, fever with increased sweating, and suicidal thoughts.
Anticonvulsant medication is commonly prescribed for migraine prevention, because they have been shown in placebo-controlled double-blind trials to be effective in some migraine sufferers.
Placebo controlled trials of both divalproex sodium and sodium valproate have shown them to be significantly better than placebo at reducing headache frequency.
Nausea, vomiting, and gastrointestinal disturbances are the most common side-effects of valproate therapy, and are slightly less common with divalproex sodium than with sodium valproate. The results of a study on the long-term safety of divalproex sodium showed premature discontinuation of the drug in 36% of patients because of either drug intolerance or ineffectivity of the drug.
Topiramate has been approved by the FDA for prevention of migraine. Studies have shown that it provides significant reductions in the frequency of migraine episodes in patients with 3-12 headaches a month
Adverse reactions related to topiramate treatment occurred in 82.5% of 328 subjects who took part in an extensive trial covering 46 different centres. Most commonly reported were paresthesia (28.8%), upper respiratory tract infection (13.8%, and fatigue (11.9%)
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