In a case series of six elderly patients (ages 65–73) suffering from frequent “drop attacks,” Braham (1994) reported on the efficacy of PB at 60 mg twice a day. None of the patients presented with any other cardiovascular or neurological diagnosis to explain these sudden falling episodes, and most benefited without suffering side effects from long-term therapy (the longest treatment period was 4 years at time of the report).

Thus, it appears that PB seems to be well tolerated and without significant neuromuscular side effects at the prescribed dose. However, as noted above, the number of patients observed for long periods with sensitive measures of motor function is insufficient to determine whether or not there is a long-term or latent effect of PB on the neuromuscular circuit.

Clinical Studies of PB and Behavioral or Cognitive Function

Molloy and Cape (1989) investigated the effects of PB on cognitive function in 15 elderly patients with Alzheimer’s disease. Their rationale for the study was the fact these patients have widespread dysfunction of central cholinergic systems necessary for memory and other higher functions. In addition, they noted that a number of previous studies with physostigmine had shown an improvement in the cognition of Alzheimer’s disease patients after treatment. Using a randomized, double-blind, crossover study design, seven elderly men and nine women (mean age 76 years) were treated with 240 mg of PB in divided doses over a 26-hour period. No significant difference in cognitive testing was found between subjects treated with PB and placebo. No side effects were observed. The authors suggested the possibility that doses were too low or the treatment period too short for observation of cognitive or untoward effects.

As noted earlier, patients with myasthenia gravis demonstrate subtle changes in cognitive function (Iwasaki et al., 1990) that are reversed with treatment, including plasmapheresis or anticholinesterases that cross the BBB (e.g., physostigmine) (Tucker et al., 1998).

Thus, these studies offer little evidence for long-term cognitive effects of PB in normal populations. The study of elderly patients with Alzheimer’s disease treated with 240 mg over 1 day showed no difference in cognitive testing between placebo and treatment subjects; no side effects were noted. However, Alzheimer’s patients would not necessarily be expected to reliably report untoward effects. Further, the possible reversal of cognitive dysfunction with anticholinesterases in myasthenics and the lack of evidence that the CNS of myasthenics responds differently to PB than that of the nonmyasthenic population might argue against adverse effects of PB on cognition in normal individuals.

Clinical Studies of PB and Cardiovascular-Related Effects

Because AChE inhibitors have been used for more than 50 years in the treatment of myasthenia gravis, clinical records may provide evidence of ad-



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