Primidone was compared to the unselective
beta adrenoceptor antagonist propranolol in the suppression of
essential tremor. In a 4-week single-blind placebo-controlled study
primidone was given in increasing doses from 62.5 mg X 1 up to 250 mg X 3 daily and
propranolol 20 mg X 3 daily. The drugs produced a similar reduction in the degree of
tremor after 2 and 1 weeks' medication respectively. This indicates that
primidone can be an alternative to
propranolol when beta-blockers are contraindicated. However,
primidone was significantly even more effective in the beginning after only 2 doses, when at the same time 10 of 13 patients showed a maximum of acute toxic side-effects producing
nausea,
vomiting, giddiness and/or sedation. Correlation analysis between the individual
tremor amplitude reductions and plasma
primidone concentrations showed on the second day a tendency towards a greater reduction in
tremor in those patients with the highest
primidone plasma concentration. By the fourteenth day
tremor had increased compared with the second day and correlation analysis between individual increase in
tremor amplitude and plasma
phenobarbital concentrations showed the highest degree of
tremor increase in those patients who had the highest levels of
phenobarbital. These and other data suggest that after the first doses,
tremor suppression and acute toxicity is related to the initial exposure to
primidone and the plasma level of the
drug itself rather than its metabolites
phenobarbital and phenylethylmalanomide. The individual
tremor frequency spectrums did not change significantly during the placebo and
propranolol periods, whereas the frequency tended to decrease during the
primidone period.