Nortriptyline Effective Dose Ranges
For depression in adults, use 75-150 mg/day as a single bedtime dose; for ADHD in children, use 1.8-2 mg/kg/day (typically 80-100 mg/day); for enuresis, tricyclic antidepressants like imipramine at 1.0-2.5 mg/kg are recommended over nortriptyline; and nortriptyline is not a first-line agent for anxiety disorders. 1, 2, 3
Depression
Adult Dosing
- Standard maintenance dose: 75-150 mg/day, administered as a single bedtime dose 1
- Elderly patients require lower dosing: maximum 40 mg/day given in divided doses (twice daily) 1
- The FDA label specifies 25 mg 3-4 times daily as the standard regimen, with gradual titration from low starting doses 4
- Alternatively, total daily dose may be given once daily; doses above 100 mg/day require plasma level monitoring 4
Therapeutic Drug Monitoring
- Target plasma concentration: 50-150 ng/mL 1
- Concentrations above 150 ng/mL are associated with decreased efficacy and increased adverse effects 1
- Doses above 150 mg/day are not recommended per FDA labeling 4
Titration Strategy
- Increase dosage using increments of the initial dose every 5-7 days until therapeutic benefits appear or side effects develop 1
- A full therapeutic trial requires 4-8 weeks before declaring treatment failure 1
- Clinical monitoring should occur within 1-2 weeks of starting therapy to assess response, adverse effects, and suicidal ideation 1
Maintenance Treatment
- Continue treatment for 4-9 months after satisfactory response for first-episode depression 1
- Recurrent depression may require years to lifetime treatment 1
ADHD
Pediatric Dosing
- Effective dose: 1.8-2 mg/kg/day (mean dose 80 mg/day in clinical trials) 2
- This dosing achieved mean serum levels of 81 ng/mL 2
- Titrate to 2 mg/kg/day over 2 weeks as tolerated 2
Efficacy Evidence
- Nortriptyline significantly reduced ADHD symptoms (p < 0.001) and oppositional symptoms (p < 0.001) in controlled trials 2
- Tricyclic antidepressants are second-line agents at best for ADHD, as they are less effective than stimulants for treating attentional and cognitive symptoms 3, 5
- They can help reduce impulsive and hyperactive behavior but do not match stimulant efficacy for core attention deficits 5
Safety Considerations
- Children tolerated robust dosing well with few clinical or cardiovascular adverse events 2
- Weight gain was noted during treatment 2
- Psychostimulants remain the treatment of choice for ADHD due to their unique effect on attention 5
Enuresis
Critical Limitation
Nortriptyline is not specifically recommended in guidelines for enuresis; imipramine is the tricyclic antidepressant with proven efficacy 3
Imipramine Dosing (Guideline-Recommended TCA)
- Dose: 1.0-2.5 mg/kg as a single bedtime dose 3
- Effectiveness: 40-60%, though relapse rate is as high as 50% 3
- This dose is lower than that used for depression 3
Nortriptyline Research Evidence
- One study showed nortriptyline statistically decreased nocturnal enuresis during intervention in children with ADHD 6
- However, enuresis relapsed after stopping nortriptyline 6
- Behavioral conditioning with alarm systems remains the first-line treatment for enuresis 3
Cardiovascular Monitoring
- Pretreatment ECG should be obtained to detect underlying rhythm disorders due to risk of cardiac arrhythmia with tricyclic antidepressants 3
- This applies even though enuresis doses are lower than depression doses 3
Anxiety Disorders
Evidence Limitations
Nortriptyline is not established as a first-line treatment for anxiety disorders 3
Clinical Context
- When ADHD and anxiety are comorbid, stimulants should be tried first 3
- If anxiety symptoms remain problematic after ADHD treatment, psychosocial interventions are preferred 3
- SSRIs may be added to stimulants for severe anxiety unresponsive to non-pharmacological treatment 3
- Tricyclic antidepressants have less compelling evidence for anxiety disorders in children and adolescents 7
Common Pitfalls and Caveats
Pediatric Use
- Nortriptyline is not FDA-recommended for pediatric patients per drug labeling 4
- Despite this, research supports its use in pediatric ADHD at 1.8-2 mg/kg/day 2
Cardiovascular Risks
- Monitor for orthostatic hypotension, especially in the first 1-2 weeks 1
- Obtain baseline ECG before initiating treatment, particularly in patients with cardiac history 1
- Monitor for QTc prolongation and cardiac conduction abnormalities 1
Clinical Characteristics
- Nortriptyline is more sedating than desipramine, making it useful for agitated depression with insomnia 1
- It has a lower risk for cardiotoxic, hypotensive, and anticholinergic effects compared to tertiary amine tricyclics like imipramine 1
Dose Conversion Warning
- Do not use 1:1 dose conversion when switching between different tricyclic antidepressants, as they have different potencies and metabolic profiles 8