A Cochrane review included 5 studies with a total of 144 subjects. Four studies assessed the efficacy of 4-aminopyridine (AP) versus placebo, one compared 3,4-aminopyridine (DAP) with active placebo. The median quality score was 3 (range 2 - 5). Of the 144 treated patients, there were six major adverse effects, including acute encephalopathy and seizures. Muscle strength by manual muscle testing (29 patients on aminopyridines improving versus four during placebo, OR 14.5, 95% CI 4.7 - 43.7), ambulation (9 vs. none), and EDSS score (13 vs none) favoured the test drugs. 47 of 136 people with MS (35%) felt improved when receiving the study drug, against 7 (5%) on placebo (OR 9.7, 95% CI 4.3 - 22.0).
Comment: The quality of evidence is downgraded by potential reporting bias (no data could be obtained from three unpublished trials involving more than 300 patients), and severe study limitations (In all but one trial the primary endpoint was not specified, and detailed outcome was only reported on endpoints found to be statistically significant).