Randomized trials of dichlorphenamide in the periodic paralyses

Although the carbonic anhydrase inhibitors have been used in the treatment of the primary periodic paralyses (PPs), their efficacy has not been demons trated in double-blind, placebo-controlled trials. Therefore, we tested the efficacy of dichlorphenamide (DCP; Daranide), a potent carbonic anhydrase inhibitor, in the treatment of episodic weakness in the primary PPs. We per formed two multicenter, randomized, double-blind, placebo-controlled crosso ver trials, one involving 42 subjects with hypokalemic periodic paralysis ( HypoPP) and the other involving 31 subjects with potassium-sensitive period ic paralysis (PSPP). In each trial, two 8-week treatment periods were separ ated by an active washout period of at least 9 weeks. The primary outcome v ariable in the HypoPP trial was the occurrence of an intolerable increase i n attack severity or frequency (end point). The primary outcome variable in the PSPP trial was the number of attacks per week. In the HypoPP trial, th ere were 13 subjects who exhibited a preference (in terms of the end point) for either DCP or placebo, and Il of these preferred DCP. In the PSPP tria l, DCP significantly reduced attack rates relative to placebo. DCP also sig nificantly reduced attack rates relative to placebo in the HypoPP subjects, We conclude that DCP is effective in the prevention of episodic weakness i n both HypoPP and PSPP.