Does propranolol (beta blocker) cause less tiredness than primidone (anticonvulsant)?

Propranolol vs Primidone: Comparative Tiredness Profile

Propranolol causes significantly MORE tiredness than primidone based on chronic use data, with 17% of patients experiencing significant chronic side effects including fatigue with propranolol versus 0% with primidone. 1

Key Evidence on Side Effect Profiles

Propranolol-Associated Fatigue

• Fatigue is a well-established and common side effect of propranolol, listed consistently across multiple cardiovascular guidelines as a potential adverse effect 2
• In essential tremor treatment, propranolol produced significant chronic side effects in 17% of patients during long-term use, with fatigue being a prominent complaint 1
• A specific study on inspiratory muscle performance found that propranolol directly caused symptoms of "tiredness" and easy fatigability in a subset of subjects, reducing their inspiratory muscle strength 3
• Beta-blockers as a class are documented to cause fatigue, sleep disturbances, and depression, which can impair school performance in children and adolescents 2

Primidone-Associated Side Effects

• Primidone showed 0% significant chronic side effects in the same comparative study where propranolol caused problems in 17% 1
• The main limitation of primidone is acute adverse reactions (occurring in 32% of patients) including nausea, vomiting, giddiness, and sedation—but these are typically initial dose reactions, not chronic fatigue 1, 4
• Acute toxic effects occur maximally after the first 2 doses and are related to initial primidone exposure rather than chronic use 4

Clinical Algorithm for Drug Selection

When fatigue/tiredness is a primary concern:

1. Choose primidone over propranolol as it demonstrates superior chronic tolerability regarding fatigue 1
2. Manage primidone's acute reactions by starting with very low doses (50 mg/day) and titrating slowly 1, 5
3. Consider that primidone may actually be more effective than propranolol for tremor reduction overall 5, 4

When propranolol must be used despite fatigue risk:

• Start with lower doses and monitor closely for fatigue symptoms 2
• Consider cardioselective beta-blockers as alternatives, though they still carry fatigue risk 2
• Be aware that fatigue from propranolol may directly depress muscle performance through mechanisms unrelated to beta-blockade 3

Important Caveats

• Acute vs chronic side effects differ dramatically: Primidone causes more acute reactions (32% vs 8%), but propranolol causes more chronic problems (17% vs 0%) 1
• The timing matters: Primidone's side effects are front-loaded and often resolve, while propranolol's fatigue tends to persist with chronic use 1, 4
• Both drugs show similar rates of tolerance development (12.5% for propranolol, 13% for primidone) 1