DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL OF LITHIUM IN EPISODIC CLUSTER HEADACHE

Lithium is widely used in the prophylaxis of episodic cluster headache without formal evidence of efficacy. Placebo-controlled clinical tria ls are not easy in conditions characterized by frequent severe pain. I n this study, it was assumed that Lithium would work quickly if at all , and placebo response would be zero. Strict diagnostic criteria exclu ded uncertain or atypical cases. Patients were male in so-far untreate d episodes expected to last for at least 3 weeks more. In a double-bli nd, placebo-controlled comparison of matched parallel groups, treatmen t was either slow-release lithium carbonate, 800 mg/day, or placebo. A fter 7 days, compliance was estimated by tablet count, blood was taken for lithium assay, efficacy was assessed (attacks stopped or substant ially improved) and adverse reactions were recorded. The study was sto pped after planned sequential analysis of the 27th patient (13 on lith ium, 14 on placebo). Estimated compliance was usually but not always g ood. Plasma lithium levels were mostly in the range 0.5-0.6 mmol/l on lithium, zero on placebo. Cessation of attacks within 1 week occurred in two patients in each group, substantial improvement in 6/14 (43%) o n placebo, 8/13 (62%; NS) on lithium. Only minor adverse events were r eported. Lithium treatment was therefore associated with a useful subj ective improvement rate but the assumptions made at outset had proved wrong. The trial was stopped because superiority over placebo could no t be demonstrated. There were lessons for future trials.