Risk of Depression With Flunarizine Use in Migraine Prophylaxis: Clinical Evidence and Management

As a calcium channel blocker, flunarizine has a long history of successful usage in migraine prophylaxis, reducing migraine attack frequency, intensity, and duration.1,2 Its pharmacological effects stem from its capacity to modulate neuronal excitability and decrease cortical spreading depression, two critical pathways in migraine pathophysiology.22 There is growing evidence that flunarizine has major neuropsychiatric side effects, such as depression, which has prompted worries regarding its long-term usage, despite its proven effectiveness in migraine prevention.3 A number of research, including randomized controlled trials, observational studies, and post-marketing monitoring studies, have shown that flunarizine does not often cause depressed symptoms in patients.4,5 Depression is more likely to occur in older patients, those who have a history of mood disorders, and those who take higher doses of flunarizine.6,7 Some theories propose that flunarizine-induced depression occurs as a result of drug buildup in the CNS, disruption of serotonergic and noradrenergic neurotransmission, and central dopaminergic blockage.8,9 Since depression symptoms are frequently reversible with a decrease in dosage or withdrawal of flunarizine.10-12 patient selection, initial psychiatric examination, and follow-up are highly important.