What is the recommended dosage and treatment protocol for propranolol (beta blocker) in a patient with recurrent and severe migraines, considering potential side effects and comorbidities such as asthma, chronic obstructive pulmonary disease (COPD), or heart failure?

Propranolol for Migraine Prevention

Propranolol is a first-line preventive medication for migraine, dosed at 80-240 mg/day in extended-release formulation or divided doses, with most patients responding to 160 mg/day. 1, 2

Indications for Starting Propranolol

Initiate propranolol when patients meet any of these criteria:

• Two or more migraine attacks per month causing disability lasting 3+ days 1
• Using acute medications more than 2 days per week, which risks medication-overuse headache 1
• Contraindications to or failure of acute treatments (triptans, NSAIDs) 1
• Uncommon migraine conditions such as hemiplegic migraine, prolonged aura, or migrainous infarction 1

Dosing Protocol

Starting Dose

• Begin with 80 mg once daily using extended-release formulation 2
• For immediate-release formulation, start with 40 mg twice daily and titrate upward 3

Titration Schedule

• Increase dose every 3-7 days until optimal response is achieved 2
• Target maintenance dose is 160 mg once daily for most patients 2, 4
• Maximum dose is 240 mg/day for migraine prevention; doses exceeding this have not been established as safe or more effective 2

Evidence for Dosing

• Meta-analysis of 2,403 patients showed 44% reduction in migraine activity with modal dose of 160 mg/day 4
• 73.5% of patients respond to low doses (≤1 mg/kg/day), meaning many patients achieve control at 80-120 mg/day 3
• Only one-third of patients require doses above 160 mg/day for adequate control 3

Absolute Contraindications

Do not use propranolol in patients with:

• Asthma or reactive airway disease - beta-blockade can precipitate bronchospasm 1
• COPD with bronchospastic component - risk of severe respiratory compromise 1
• Decompensated heart failure - negative inotropic effects worsen cardiac output 1
• Second- or third-degree AV block without pacemaker 1
• Severe bradycardia (heart rate <50 bpm) 1
• Cardiogenic shock 1

Relative Contraindications and Cautions

Cardiovascular Considerations

• First-degree AV block or sinus bradycardia - monitor heart rate and consider lower doses 1
• Peripheral vascular disease - may worsen claudication symptoms 1
• Raynaud's phenomenon - beta-blockade can exacerbate vasospasm 1

Metabolic Concerns

• Diabetes mellitus - propranolol masks hypoglycemic symptoms (tachycardia, tremor) and may prolong hypoglycemia 1
• Hyperthyroidism - abrupt withdrawal can precipitate thyroid storm 1

Psychiatric Conditions

• Active depression - propranolol can worsen depressive symptoms in susceptible patients 1

Alternative First-Line Agents When Propranolol is Contraindicated

If asthma/COPD present:

• Topiramate 50-100 mg/day (start 25 mg daily, increase by 25 mg weekly) 1
• Candesartan 16-32 mg/day - particularly useful with comorbid hypertension 1

If heart failure present:

• Candesartan 16-32 mg/day 1
• Topiramate 50-100 mg/day 1

If depression present:

• Avoid propranolol and amitriptyline - both can worsen mood 1
• Use topiramate or candesartan instead 1

Implementation Strategy

Trial Period

• Allow 2-3 months at target dose before determining efficacy - this is critical as many patients discontinue prematurely 1
• Use headache diaries to track frequency, severity, and disability - objective measurement prevents premature abandonment 1

Success Criteria

• ≥50% reduction in monthly migraine days is considered successful prophylaxis 1
• Reduced severity and duration of attacks even if frequency unchanged 1
• Decreased need for acute medications to <2 days per week 1

Duration of Therapy

• Continue for 6-12 months after achieving stable control 1
• Consider tapering after this period to determine if ongoing therapy is needed 1
• Taper gradually over several weeks - abrupt discontinuation can cause rebound hypertension and tachycardia 2

Common Pitfalls to Avoid

Dosing Errors

• Starting at too high a dose (>80 mg/day) leads to poor tolerability and early discontinuation 1, 3
• Inadequate trial duration (<2 months) - many clinicians and patients give up too early 1
• Failing to titrate to effective dose - stopping at 80 mg when 160 mg is needed 3

Monitoring Failures

• Not recognizing medication-overuse headache - patients using acute medications ≥10 days/month for triptans or ≥15 days/month for NSAIDs will not respond to preventive therapy until overuse is addressed 1
• Ignoring comorbidities - failing to screen for asthma, heart failure, or depression before prescribing 1

Patient Education Gaps

• Not counseling about delayed onset of benefit - patients expect immediate results and discontinue prematurely 1
• Failing to warn about withdrawal effects - abrupt cessation can cause rebound symptoms 2

Side Effects and Management

Common Side Effects

• Fatigue and lethargy - often improves after 2-4 weeks; if persistent, reduce dose 3
• Sleep disturbances and vivid dreams - take dose in morning rather than evening 1
• Cold extremities - usually mild and tolerable 3
• Sexual dysfunction - may require switching to alternative agent 1

Serious Adverse Effects Requiring Discontinuation

• Severe bradycardia (<50 bpm with symptoms) 1
• Hypotension (systolic <90 mmHg with symptoms) 1
• Bronchospasm in undiagnosed asthma 1
• Severe depression or suicidal ideation 1

When to Switch to Second-Line Agents

Consider amitriptyline 30-150 mg/day if:

• Mixed migraine and tension-type headache - amitriptyline treats both 1
• Comorbid insomnia - sedating effect is beneficial 1
• Propranolol contraindicated or failed after adequate trial 1

Consider valproate/divalproex 500-1500 mg/day if:

• Multiple first-line agents have failed 1
• Patient is male or not of childbearing potential - strictly contraindicated in women who can become pregnant due to severe teratogenic effects 1

Special Populations

Elderly Patients

• Start with lower doses (40 mg/day) due to increased sensitivity 5
• Monitor closely for bradycardia and hypotension - elderly have reduced baroreceptor sensitivity 5
• Screen carefully for heart block and heart failure - more common in this population 5

Patients with Diabetes

• Counsel about masking of hypoglycemic symptoms - tachycardia and tremor will be blunted 1
• Monitor blood glucose more frequently during titration 1
• Consider cardioselective beta-blocker (metoprolol) as alternative, though evidence is similar 6