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

Abstract

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.

Pharmacotherapy of Essential Tremor

“…There is no clear correlation between the dose and efficacy and a long-term use of 250 mg/day versus 750/day did not result in a higher proportion of patients with better tremor control 113. This is an agreement with studies that did not find any correlations between the plasma levels and the degree of tremor control 106. Average tremor improvement is up to 75% reduction from the baseline, even though most studies reported approximately 50% improvement 106,108–113.…”

“…Serum concentrations of 5 to 12 μg/mL are recommended to effectively control seizures, while significant efficacy for ET has been observed at levels less than 5 μg/mL 100. Moreover, there is no clear correlation between plasma levels and efficacy for tremor control 106. Primidone undergoes partial hepatic transformation through the cytochrome oxidase complex to phenobarbital and PEMA.…”

Randomized trial comparing primidone initiation schedules for treating essential tremor

“…Essential tremor is a common complaint 1. Primidone is one of the very few medications consistently shown to reduce essential tremor 2–7. It is the first choice treatment for some neurologists,8 and is often prescribed if beta‐blockers are contraindicated or fail to control tremor.…”

Practice Parameter: Therapies for essential tremor [RETIRED]

“…Another 4-week prospective, patient-blinded, placebo-controlled study in 13 patients with ET compared the effects of placebo, propranolol 20 mg three times a day, and primidone 250 mg three times a day. 18 Both primidone and propranolol significantly reduced tremor, whereas placebo had no effect. There was equivalent reduction in tremor magnitude after 1 week of propranolol treatment and 2 weeks of primidone treatment (class III).…”