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Bamford CC et al. - Treatment should always begin with low doses and be gradually increased to optimal dosing, which then should be maintained for 2 to 3 months to evaluate effectiveness. Medications with the best evidence for efficacy in the prevention of migraine are amitriptyline, propranolol, timolol, valproate, and topiramate. Although all migraine preventive medications are nonspecific and have multiple potential mechanisms for their effects, they often share a tendency to reduce central neuronal hyperexcitability by inhibiting excitatory neurotransmitters, such as glutamate and norepinephrine, increasing inhibitory tone via GABA, reducing the likelihood of cortical spreading depression, or favorably altering channelopathies or mitochondriopathies thought to be intrinsic to migraine pathophysiology.

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