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.