Primidone and propranolol in essential tremor: a study based on quantitative tremor recording and plasma anticonvulsant levels.

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.