BACKGROUND: Several nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective in the treatment of migraine. However, few commercially available NSAIDs can be administered IV. Lysine clonixinate (LC), an NSAID derived from nicotinic acid, has been proved effective in various algesic syndromes (eg, renal colic, muscular pain, nerve compression, odontalgia). The oral formulation of LC has been shown to be effective in the treatment of migraine of moderate severity. OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of the IV formulation of LC in the treatment of severe migraine. METHODS: This double-blind, randomized, placebo-controlled, prospective study enrolled patients with severe migraine (without aura) as defined by the criteria of the International Headache Society. When patients presented to a neurology hospital with an outpatient headache unit (Instituto de Neurologia Deolindo Couto, Rio de Janeiro, Brazil) with a severe migraine attack that had lasted <4 hours, they were randomized to 1 of 2 groups (IV placebo [25 mL of 0.9% saline] or IV LC [21 mL of 0.9% saline plus 4 mL of LC 200 mg]). Headache intensity and adverse effects (AEs) were assessed before (0 minute) and 30, 60, and 90 minutes after study drug administration. Rescue medication was available 2 hours after study drug administration, and its use was compared between groups. RESULTS: Thirty-two patients (23 women, 9 men; mean [SD] age, 32 [2] years; range, 18-58 years) entered the study. Twenty-nine patients (21 women, 8 men; mean [SD] age, 32 [2] years; range, 18-56 years) completed the study. Three patients (all in the placebo group) did not complete the study (1 patient was unable to rate the pain severity after drug administration and 2 patients refused IV drug administration). Among study completers, 17 patients received LC and 12 placebo. At 30 minutes, 1 patient (8.3%) in the placebo group and 5 patients (29.4%) in the LC group were pain free; the between-group difference was not statistically significant. At 60 and 90 minutes, respectively, 3 (25.0%) and 5 (41.7%) patients in the placebo group and 12 (70.6%) and 14 (82.4%) patients in the LC group were pain free (P = 0.021 and P = 0.028 between groups at 60 and 90 minutes, respectively). Six patients (50.0%) in the placebo group and 1 patient (5.9%) in the LC group required rescue medication at 2 hours (P = 0.010 between groups). Three patients (25.0%) in the placebo group experienced AEs, including vomiting, dizziness, and malaise (1 patient [8.3%] each); 11 patients (64.7%) in the LC group experienced 1 AE, including burning pain at the injection site (5 patients [29.4%]), heartburn (4 patients [23.5%]), and dizziness and malaise (1 patient [5.9%] each) (P = 0.025). CONCLUSIONS: NSAIDs administered by the IV route cannot be used routinely in an outpatient environment, although an attempt to improve drugs in this class is clearly justified. This study demonstrated that IV LC was effective and well tolerated in the treatment of severe migraine attacks. This finding differs from results with the oral formulation, which is effective only in migraine of moderate severity.