Propranolol In Essential Tremor Research Articles

Mechanisms of tremor-modulating effects of primidone and propranolol in essential tremor

IntroductionPrimidone and propranolol are primary treatments for essential tremor, however the exact mechanisms underlying their efficacy are not fully elucidated. Understanding how these medications alleviate tremor may guide the development of additional pharmacologic treatments. Our prospective observational study employed transcranial magnetic stimulation (TMS) to explore mechanisms of primidone and propranolol effects in essential tremor. Eyeblink classical conditioning (EBCC) was tested as a potential predictor of treatment response. MethodsPatients with essential tremor underwent two evaluations: prior to commencing primidone or propranolol and following a minimum of three months of treatment. Tremor severity was assessed using accelerometry and clinically. TMS was employed to study changes in corticospinal excitability - resting and active motor thresholds, resting and active input/output curves and intracortical excitability - cortical silent period (CSP), short interval intracortical inhibition intensity curve (SICI), long interval intracortical inhibition (LICI), intracortical facilitation (ICF), and short afferent inhibition (SAI). EBCC, a marker of cerebellar function, was studied at baseline. ResultsOf the 54 enrolled patients (28 primidone, 26 propranolol), 35 completed both visits. Primidone effect on decreasing hand tremor was associated with decreased corticospinal excitability, prolongation of CSP, increased LICI, increased SAI and decreased SICI. Propranolol effect on hand tremor was associated with decreased corticospinal excitability and increased SAI. Better EBCC at baseline predicted better response to primidone. ConclusionsPrimidone exerts its therapeutic effects by blocking voltage-gated sodium channels and by modulating GABA-A and GABA-B intracortical circuits. Propranolol's central effects are likely mediated via noradrenergic modulation of GABA outflow.

Propranolol and essential tremor: Rôle of the membrane effect

d-propranolol is almost devoid of beta-blocking effect but has the same membrane stabilizing properties as the dl-form. In order to study the importance of membrane stabilizing activity versus beta blockade in the therapeutical effect of propranolol on essential tremor, we compared d-propranolol with dl-propranolol in 24 patients in a placebo-controlled double-blind cross-over study. dl-propranolol reduced tremor intensity better than d-propranolol. The d-form did not significantly differ from placebo in its effects on tremor, although it did reduce the heart rate slightly. It is concluded that the membrane effect is not important in the therapeutic effect of propranolol in essential tremor.

Clinical and computer-based assessment of long-term therapeutic efficacy of propranolol in essential tremor

Despite a large number of studies demonstrating the effectiveness of propranolol in relieving essential tremor (ET) the long-term therapeutic outcome of these patients remains poorly defined. The results of a one-year follow-up study in 18 patients with mild to severe ET performed by using clinical and computer-based methods of assessment indicate that the initial therapeutic benefit of propranolol is apparently retained. However, following 3-6 months of sustained treatment a proportion of patients required an increase in daily dosage of propranolol in order to maintain adequate symptomatic control of tremor, indicating a relative decrease in tremorolytic efficacy of the drug possibly due to long-term tolerance.

A multicenter randomized crossover multiple-dose comparison study of arotinolol and propranolol in essential tremor

Background. A new medication is needed to treat essential tremor. Preliminary evidence suggests that arotinolol may be effective in the treatment of this disorder. Objective. To study the effect of arotinolol and propranolol in a crossover, multiple dose comparative trial of patients with essential tremor. Patients and methods. One hundred and seventy-five outpatients, with essential tremor were included in the study; 161 patients completed the study. Patients were identically evaluated at eight consecutive visits. The study consisted of two treatments, which were arranged according to a crossover design that evaluated the dose of each (arotinolol 10 mg per day and propranolol 40 mg per day, arotinolol 20 mg per day and propranolol 80 mg per day, arotinolol 30 mg per day and propranolol 160 mg per day). Each course of treatment lasted 6 weeks. Major outcome evaluations consisted of a self-reported disability scale, and motor performance score obtained before drug intake and 14 days after each treatment. The treatment effects were evaluated by analysis of variance using the Hills-Armitage test. Results. Arotinolol was found to be as effective as propranolol at reducing tremor. Drug effects as evaluated using motor-task performance scores revealed that arotinolol had a more significant effect than propranolol. Conclusions. Arotinolol may be more useful than propranolol for the treatment of essential tremor.

Time course of a single oral dose of propranolol in essential tremor

Time course of a single oral dose of propranolol in essential tremor

Time course of a single oral dose of propranolol in essential tremor.

We studied the effects of a single oral dose (120 mg) of propranolol on essential tremor in 12 patients. Postural hand tremor was recorded by an accelerometer, and its amplitude and frequency determined by spectral analysis. Variable patterns of individual responses gave a mean reduction of tremor amplitude of 50% at 2 hours. Tremor was suppressed as long as 8 hours in some patients. Similar tremor reduction was found on chronic therapy. Even without treatment, tremor amplitude varied from 30 to 50%. A single oral dose of propranolol produces a rapid and sustained reduction of essential tremor, but there are diurnal fluctuations of tremor intensity regardless of treatment.

Long-acting propranolol in essential tremor.

Long-acting propranolol (propranolol-LA) was compared with propranolol in divided doses in 18 patients with essential tremor. Three patients were unresponsive to both preparations. Propranolol-LA was preferred by 87% of patients for ease of administration and by 67% for tremor control. Propranolol-LA provided similar (53%), and in some patients greater (47%), reduction of tremor amplitude than divided dosing. Propranolol-LA should be a useful drug in essential tremor.