Laboratory Monitoring for Nortriptyline
Regular monitoring of plasma nortriptyline concentrations is strongly recommended, with therapeutic levels maintained between 50-150 ng/mL for optimal efficacy and safety. 1
Baseline Laboratory Tests Required
Before initiating nortriptyline therapy, the following baseline laboratory tests should be performed:
- Complete blood count (CBC)
- Thyroid function tests
- Liver function tests
- Renal function tests (BUN, creatinine)
- Electrocardiogram (ECG), especially in patients over 40 years or with cardiac history
Ongoing Monitoring Requirements
Plasma Drug Concentration Monitoring
- Measure plasma nortriptyline levels after reaching steady state (approximately 5-7 days)
- Target therapeutic range: 50-150 ng/mL 1
- Timing of blood draw: 12-16 hours after the last dose (typically morning sample after evening dose)
- Frequency:
- Initially after reaching steady state
- After any dose adjustment
- Every 3-6 months during maintenance therapy
- When clinical response is inadequate
- When adverse effects occur despite standard dosing
Metabolite Monitoring
- Consider monitoring 10-hydroxynortriptyline (active metabolite) in elderly patients and those with renal impairment
- Higher concentrations of this metabolite have been associated with cardiotoxicity even when nortriptyline levels are within therapeutic range 1, 2
Cardiac Monitoring
- ECG monitoring is recommended, especially in patients with pre-existing cardiac conditions
- Monitor for QTc prolongation, conduction abnormalities, and changes in heart rate 3
- Significant increases in heart rate (>16 beats per minute) may correlate with higher tricyclic levels 3
Renal Function Monitoring
- Regular monitoring of renal function is particularly important as metabolite elimination is affected by renal impairment 4
- The ratio of E-10-hydroxynortriptyline to nortriptyline is inversely correlated with creatinine clearance 2
Hepatic Function Monitoring
- Periodic liver function tests (every 3-6 months) are recommended as nortriptyline is extensively metabolized by the liver 5
Special Populations Requiring More Intensive Monitoring
More frequent monitoring is recommended for:
- Elderly patients (>65 years)
- Patients with renal or hepatic impairment
- Children and adolescents
- Patients with cardiovascular disease
- Patients on multiple medications with potential interactions
- Patients with genetic variations affecting drug metabolism (CYP2D6)
Clinical Considerations
- Clinical findings should predominate over plasma concentrations when determining dosage changes 1
- Doses above 150 mg per day are not recommended due to increased risk of adverse effects 1
- Single-dose pharmacokinetic testing may help predict steady-state levels and optimize dosing more rapidly 6, 7
- Patients should be monitored for signs of serotonin syndrome, particularly when combined with other serotonergic medications 8
By following these monitoring guidelines, clinicians can optimize nortriptyline therapy while minimizing the risk of adverse effects and toxicity.