Randomized trials of dichlorphenamide in the periodic paralyses. Working Group on Periodic Paralysis. Improvement of muscle strength in familial hypokalaemic periodic paralysis with acetazolamide.
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. A double blind cross-over study of eight patients with familial hypokalaemic periodic paralysis was made to assess the influence of acetazolamide on muscle strength. All patients had a reduced interictal muscle fibre conduction velocity. Five patients had no attacks at the time of the study. One patient withdrew from the study because of an adverse reaction. The muscle strength of 11 muscle groups was measured with a hand-held dynamometer. The sum of force improved significantly in the seven patients (mean increase: 17%, p less than 0.05; 95% confidence interval: 7.2-26.8%). Endurance tests showed an improvement in the performance of 30 full kneebends. Surface EMG measurement showed no change in the muscle fibre conduction velocity or power spectra during treatment. The integrated EMG showed a (non significant) mean increase of 21%.
The largest included study that met our inclusion criteria suggested that DCP was effective in the prevention of episodic weakness in both hypokalemic and hyperkalemic periodic paralyses. The other two studies provide some evidence that either acetazolamide or pinacidil may improve muscle strength. However we still lack sufficient evidence to provide full guidelines for the treatment of people with periodic paralysis.