Beta Blockers For Tremors

Introduction

A tremor is a shaking or vibrating movement that happens involuntarily (out of the control of the human experiencing it) in a part of the body. It usually has a steady speed but can vary in strength. It occurs when muscles that work against each other contract and relax alternately. Tremors are the most common type of movement disorders, and essential tremor is the most frequent neurological reason for shaking during activities or holding a posture.¹

Typically, it presents itself as shaking in both hands when holding them still. It includes shaking when you are moving or at rest. At first, both arms are usually affected equally, but as the condition worsens, it can also affect the head and voice (and less commonly, the legs, jaw, face, and trunk). Despite its non-threatening effect on life expectancy, it often leads to public embarrassment, and in a small percentage of patients, also serious disability. Symptoms are generally progressive and potentially disabling, often driving patients to change jobs or request early retirement.¹

The reason behind essential tremors is mostly unexplained. About half of the cases of essential tremor appear to be caused by a genetic mutation; although, a specific gene has not been identified. This form is referred to as familial tremor. The fact that essential tremors can start at different ages, occur intermittently in some cases, and do not always affect identical twins in the same way indicates that environmental factors may also be involved.¹

The diagnosis of essential tremors is based on clinical features and the exclusion of alternative diagnoses. The main criteria involve shaking in both hands and forearms while performing actions and the absence of other neurologic signs. Other information strongly suggestive of essential tremors includes tremors lasting for more than three years (considered as a long duration), a positive family history of essential tremors, and a beneficial response to alcohol.¹

Patients who are not severely affected by the tremors may decide not to undergo treatment. However, some patients who have no functional limitations desire treatment because their tremor is a significant reason for embarrassment. Options for patients with remarkable difficulty in performing tasks include non-medical, medical, or interventional therapy.¹

This article will concentrate on the medical treatment for essential tremors, being beta-blockers. We'll explore what they are, the different types, how they work, potential side effects when to avoid them, and other interesting facts.

What are beta blockers?

Beta-blockers, as a class of medications, are mainly used to treat cardiovascular diseases and other conditions. Beta-blockers are indicated and have FDA approval for the treatment of tachycardia, hypertension, myocardial infarction, congestive heart failure, cardiac arrhythmias, coronary artery disease, hyperthyroidism, essential tremor, aortic dissection, portal hypertension, glaucoma, migraine prevention, and other conditions.²

Beta-blockers work by competing with substances like epinephrine and norepinephrine for specific sites called beta-receptors. These blockers are divided into "selective" and "non-selective" types, depending on whether they block both beta-1 receptors, which are primarily present in the heart muscle, and beta-2 receptors found in bronchial and smooth muscles.³

Non-selective beta-blockers encompass propranolol, nadolol, pindolol, labetalol, penbutolol, sotalol, carvedilol, and timolol. On the other hand, beta-1 selective blockers include metoprolol, atenolol, acebutolol, betaxolol, esmolol, bisoprolol, and nebivolol.³

Propranolol for essential tremors

Among the drugs of first choice for essential tremors is propranolol, a non-selective beta-blocker. The exact mechanism of how propranolol stops tremors has not been fully established. It is widely accepted that essential tremor comes from the central nervous system. The effectiveness of propranolol in treating essential tremors is likely due to its ability to block peripheral noncardiac beta-2 receptors located in the muscle spindles.⁴

Dosing and clinical approach 

While the FDA recommends initiating propranolol at a dosage of 40 mg twice daily, it is often considered advisable to commence at a lower dose of 20 mg twice daily. The dosage can then be adjusted based on the medication's effectiveness and the patient's tolerance. The initiation dose in elderly people should be even lower, and 10 mg twice a day may be better tolerated in these patients. The target dose differs and it is important to talk about treatment goals with a healthcare professional before starting medication.⁴

Propranolol LA, or the long-acting propranolol, can be directly started at 80 mg/day dose, but it may be reasonable to start a regular form and when the stable dose is achieved, switch to a long-acting form. A direct comparison of both forms of this medication revealed that 87% of treated patients preferred a long-acting form, and its usage may enhance overall adherence.⁴

Patients with a mild tremor that is commonly aggravated by stress or anxiety may be initially treated on an as-needed basis with a single dose of 10 or 20 mg.⁴

Side effects of propranolol

The most common adverse effects associated with propranolol use include lightheadedness with symptomatic hypotension and bradycardia, fatigue, erectile dysfunction, drowsiness and sedation, shortness of breath during physical activity, and headaches.⁴

When should propranolol be avoided?

Propranolol should be completely avoided in patients with cardiogenic shock or unstable congestive heart failure, sinus bradycardia, greater than first-degree atrioventricular block, asthma, and known hypersensitivity to propranolol. This medication can be cautiously used in a stable congestive heart failure with left ventricular systolic dysfunction.⁴ 

Administration of propranolol and calcium channel blockers at the same time should be avoided. Propranolol may also mask the symptoms of hypoglycemia, such as tachycardia and blood pressure changes, in patients with diabetes mellitus.⁴

Sudden discontinuation of propranolol may worsen angina pectoris, and, in some cases, acute myocardial infarctions have been reported. Thus, the dose should be reduced gradually. 

Propranolol is classified by the FDA as pregnancy risk category C, where animal studies have suggested a potential risk to the fetus.⁴

Other beta-blockers for essential tremors

Even though only propranolol is supported by sufficient data to consider it as a first-line therapy, other non-selective and selective beta-blockers have been trialled in essential tremors. None of these are FDA-approved for tremor control yet.⁴

Nadolol, administered once daily, is a non-selective beta-blocker. In a small study involving 10 essential tremor patients, it was observed that doses of 120 or 240 mg proved effective.

Notably, this efficacy was evident only in individuals who had previously exhibited a positive response to propranolol.⁴

Sotalol is another non-selective beta-blocker that was directly compared with metoprolol and atenolol but not propranolol. Efficacy of sotalol was observed at doses ranging from 75 to 200 mg/day using a twice-daily dosing schedule.⁴

Atenolol is a beta-1 selective blocker that can help control tremors in people at risk of bronchospasms. It is taken once a day. Atenolol has a lower risk of causing side effects in the central nervous system compared to propranolol, thanks to its low lipid solubility. However, using higher doses may reduce its selectivity for beta-1 receptors. Atenolol showed a 37% reduction in tremors at doses ranging from 50 to 150 mg/day. In a direct comparison study, atenolol was found to be less effective than propranolol, emphasising the importance of acting on adrenergic peripheral beta-2 receptors.⁴

Metoprolol is another selective beta-blocker. Although single-dose studies suggested equal efficacy of metoprolol with propranolol, propranolol was proven superior upon more chronic administration.⁴

Overall, other beta-blockers are inferior in efficacy to propranolol. Metoprolol and atenolol may be considered in patients who experience bronchospasm when treated with propranolol, but their tremor control tends to be much less robust and transient.⁴

Concluding remarks

• Essential tremor is a common movement disorder characterised by involuntary shaking, often affecting hands initially and progressing to other body parts.
• While the cause is largely unknown, genetic factors are believed to contribute to about half of the cases (familial tremor), and environmental factors may also play a role.
• Diagnosis is based on clinical features, including shaking in both hands and forearms during activities, absence of other neurologic signs, a positive family history, tremor lasting over 3 years, and a positive response to alcohol.
• Essential tremors can lead to embarrassment and, in some cases, serious disability, impacting patients' work and daily life.
• Propranolol, a non-selective beta-blocker, is a common medical treatment for essential tremor, working by blocking peripheral noncardiac beta-2 receptors in muscle spindles.
• The FDA recommends initiating propranolol at 40 mg twice daily, but starting at a lower dose may be considered, with adjustments based on effectiveness and tolerance.
• Propranolol may have side effects, including lightheadedness, bradycardia, fatigue, erectile dysfunction, drowsiness and headaches.
• It should be avoided in certain conditions such as cardiogenic shock, unstable congestive heart failure, sinus bradycardia, greater than first-degree atrioventricular block, asthma, and known hypersensitivity.
• Sudden discontinuation of propranolol should be avoided, as it may worsen angina pectoris, and gradual reduction is recommended.
• Other beta-blockers like nadolol, sotalol, atenolol, and metoprolol have been trialled, but propranolol is the only one with sufficient data to be considered a first-line therapy.
• Individual patient factors and the risk of bronchospasm may influence the choice of beta-blockers for essential tremor treatment.

Summary

Essential tremor, a common movement disorder, often causing embarrassment and disability, is treated medically with beta-blockers like propranolol. Propranolol, a non-selective beta-blocker, effectively alleviates tremors by blocking peripheral beta-2 receptors. Starting at lower doses is advisable, adjusting based on effectiveness and tolerance.

Side effects include lightheadedness, bradycardia, and fatigue. Propranolol should be avoided in specific conditions like heart failure and asthma. Other beta-blockers like nadolol and atenolol have been trialed but lack FDA approval for tremor control. Individual patient factors and risk of bronchospasm influence treatment choice.