How should nortriptyline be initiated and monitored in a patient with coronary artery disease, prior myocardial infarction, heart failure, or documented arrhythmia or conduction abnormality?

Starting Nortriptyline in Patients with Cardiac History

Nortriptyline should not be initiated in patients with recent myocardial infarction, significant conduction abnormalities (beyond first-degree AV block or isolated hemiblock), or decompensated heart failure, but can be cautiously used in stable coronary artery disease with careful monitoring of ECG, blood pressure, and plasma drug levels. 1, 2

Absolute Contraindications

The FDA label explicitly contraindicates nortriptyline in specific cardiac scenarios 1:

• Recent myocardial infarction - One case report documented acute MI after just two 10-mg doses of nortriptyline in an elderly patient 3
• Decompensated heart failure - The drug's anticholinergic and type IA antiarrhythmic properties pose excessive risk 1
• Severe conduction disturbances (unless pacemaker present) - Risk of complete heart block 1

Relative Contraindications Requiring Extreme Caution

Patients with the following conditions require close supervision but are not absolute contraindications 1:

• Stable coronary artery disease - Tricyclic antidepressants carry risks similar to type IA antiarrhythmics (like those that increased mortality in the CAST trial), though nortriptyline can be used with monitoring 4
• History of arrhythmias - The drug prolongs conduction time and can cause sinus tachycardia 1
• Bundle branch block or bifascicular block - Higher risk but manageable with serial ECG monitoring 5

Pre-Initiation Evaluation

Before starting nortriptyline, obtain 1, 5:

• Baseline 12-lead ECG - Measure PR interval, QRS duration, and QT interval 5
• Blood pressure (supine and standing) - To establish baseline orthostatic changes 2
• Cardiac history review - Document any prior MI, arrhythmias, heart failure, or conduction abnormalities 1

Initiation Protocol

Start at the lowest possible dose and titrate slowly 1, 5:

• Begin with 10-25 mg daily in elderly or cardiac patients (lower than standard starting doses) 3, 6
• Increase by 10-25 mg every 5-7 days based on tolerance 5
• Target therapeutic plasma levels of 190-570 nmol/L (50-150 ng/mL) 2
• Maximum dose typically 75-100 mg daily in cardiac patients (lower than the 150 mg used in healthy adults) 3

Monitoring Requirements

Serial monitoring is mandatory throughout treatment 5, 2:

ECG Monitoring

• Repeat ECG after each dose increase - Monitor for QRS widening (>25% increase is concerning), PR prolongation, or new conduction abnormalities 5
• Weekly ECGs during titration phase in patients with pre-existing conduction disease 5
• Watch specifically for: sinus tachycardia (11% increase in heart rate is typical), new bundle branch blocks, or AV block progression 2

Blood Pressure Monitoring

• Check orthostatic vital signs at each visit - Nortriptyline causes significantly less orthostatic hypotension than imipramine (5% vs 50% intolerance rate) 6
• Measure supine and standing BP at baseline and after each dose adjustment 2

Plasma Drug Levels

• Obtain plasma nortriptyline levels once therapeutic dose is reached to ensure levels are 190-570 nmol/L 2
• Levels above this range increase cardiac toxicity risk without improving efficacy 2

Specific Cardiac Populations

Stable Coronary Artery Disease

Nortriptyline can be used but with heightened vigilance 2:

• In a direct comparison study, nortriptyline caused adverse cardiac events in 18% of patients with ischemic heart disease versus 2% with paroxetine 2
• However, 55% of patients achieved remission, demonstrating efficacy 2
• Consider alternative antidepressants (SSRIs) as first-line in this population 4, 2

Left Ventricular Dysfunction

Nortriptyline is relatively safe in stable LV impairment 6:

• A study of 21 patients with left ventricular impairment showed no change in ejection fraction with nortriptyline treatment 6
• Only 5% developed orthostatic hypotension (compared to 50% with imipramine) 6
• This applies only to stable, compensated heart failure, not acute decompensation 1

Conduction Abnormalities

Risk stratification based on conduction defect severity 5:

• First-degree AV block or isolated hemiblock - Low risk, can proceed with standard monitoring 5
• Bundle branch block or bifascicular block - Higher risk but manageable with serial ECGs and plasma level monitoring 5
• Complete heart block or Mobitz II - Absolute contraindication unless pacemaker present 1

Critical Warnings

The FDA emphasizes cardiovascular supervision is mandatory 1:

• Nortriptyline produces sinus tachycardia and prolongs conduction time 1
• Myocardial infarction, arrhythmia, and strokes have occurred during treatment 1
• The drug has type IA antiarrhythmic properties, similar to agents that increased post-MI mortality in clinical trials 4

Drug Interactions

• Avoid concurrent use with other QT-prolonging agents - Additive risk of arrhythmias 7
• Thyroid medication requires great care due to risk of cardiac arrhythmias 1
• Guanethidine and similar antihypertensives may have blocked effects 1

When to Stop or Avoid Initiation

Discontinue immediately if 1, 3:

• New ECG changes suggesting acute coronary insufficiency (T-wave inversions, ST changes) 3
• Development of new bundle branch block or progression of conduction disease 3
• Sustained tachycardia with symptoms 3
• Orthostatic hypotension causing syncope or falls 6

Alternative Considerations

SSRIs (particularly paroxetine) are safer alternatives in cardiac patients 4, 2:

• Paroxetine showed no sustained effects on heart rate, rhythm, or heart rate variability in ischemic heart disease patients 2
• Adverse cardiac event rate was 2% with paroxetine versus 18% with nortriptyline 2
• Consider SSRIs as first-line unless specific contraindications exist 4