Randomized trials of dichlorphenamide in the periodic paralyses

TLDR

Although carbonic anhydrase inhibitors have been used for primary periodic paralyses, their efficacy has not been demonstrated in double‑blind, placebo‑controlled trials. We tested the efficacy of dichlorphenamide (DCP) in treating episodic weakness in primary periodic paralyses. Two multicenter, randomized, double‑blind, placebo‑controlled crossover trials were conducted—one with 42 hypokalemic periodic paralysis patients and one with 31 potassium‑sensitive periodic paralysis patients—each comprising two 8‑week treatment periods separated by at least a 9‑week washout, with primary outcomes of intolerable attack worsening in HypoPP and weekly attack counts in PSPP. DCP was preferred over placebo by 11 of 13 subjects in the HypoPP trial and significantly lowered attack rates in both HypoPP and PSPP patients, demonstrating its effectiveness in preventing episodic weakness.

Abstract

Although the carbonic anhydrase inhibitors have been used in the treatment of the primary periodic paralyses (PPs), their efficacy has not been demonstrated 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 performed two multicenter, randomized, double-blind, placebo-controlled crossover trials, one involving 42 subjects with hypokalemic periodic paralysis (HypoPP) and the other involving 31 subjects with potassium-sensitive periodic paralysis (PSPP). In each trial, two 8-week treatment periods were separated by an active washout period of at least 9 weeks. The primary outcome variable in the HypoPP trial was the occurrence of an intolerable increase in 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, there were 13 subjects who exhibited a preference (in terms of the end point) for either DCP or placebo, and 11 of these preferred DCP. In the PSPP trial, DCP significantly reduced attack rates relative to placebo. DCP also significantly reduced attack rates relative to placebo in the HypoPP subjects. We conclude that DCP is effective in the prevention of episodic weakness in both HypoPP and PSPP.