What is Nortriptyline (tricyclic antidepressant) used for?

Nortriptyline Clinical Uses

Nortriptyline is primarily indicated for the treatment of major depressive disorder, particularly endogenous depression, and serves as an effective second-line agent for neuropathic pain and irritable bowel syndrome. 1

Primary Indication: Depression

The FDA has approved nortriptyline specifically for the relief of symptoms of depression, with endogenous depressions being more likely to respond than other depressive states. 1

Efficacy in Depression

• Nortriptyline demonstrates approximately 40% response rates in treatment-resistant depression after patients have failed 1-5 adequate antidepressant trials, making it a valuable option when SSRIs fail. 2
• In elderly patients with recurrent major depression, maintenance therapy with nortriptyline at plasma levels of 80-120 ng/ml prevents recurrence in approximately 71% of patients over 3 years. 3
• The therapeutic plasma concentration range is well-established at 50-150 ng/ml, with optimal efficacy around 100 ng/ml. 4

Dosing Strategy for Depression

• Start at 10-25 mg at bedtime and titrate gradually every 3-7 days. 5
• Target dose ranges from 25-100 mg daily, with maximum recommended dose of 150 mg/day. 5
• Once-daily dosing at 150 mg is as effective as divided doses with comparable side effects, offering administrative advantages. 6
• Therapeutic drug monitoring is recommended when approaching maximum doses to ensure plasma levels remain within the therapeutic window. 5

Second-Line Indication: Neuropathic Pain

Nortriptyline is preferred over amitriptyline for neuropathic pain management due to equivalent efficacy with superior tolerability, particularly fewer anticholinergic effects. 5

• Start at lower doses (10-25 mg at bedtime) for pain management and increase gradually every 3-7 days. 5
• Pain relief often occurs at doses lower than those required for depression treatment. 5
• Maximum dose for neuropathic pain is 150 mg/day. 5

Second-Line Indication: Irritable Bowel Syndrome

Tricyclic antidepressants, including nortriptyline, are effective second-line treatments for global IBS symptoms and abdominal pain, functioning as gut-brain neuromodulators. 7

• Initiate at low doses (e.g., 10 mg once daily) and titrate gradually. 7
• Careful explanation of the rationale for use is required, as patients may be confused about using an "antidepressant" for gastrointestinal symptoms. 7
• TCAs work through peripheral effects on gastrointestinal function and central modulation of pain perception. 7

Advantages Over Other Tricyclics

Nortriptyline has fewer anticholinergic side effects compared to tertiary amine TCAs like amitriptyline and imipramine, making it better tolerated, especially in elderly patients. 5, 8

• Less sedation, dry mouth, constipation, urinary retention, and confusion compared to amitriptyline. 5
• Nortriptyline is the active metabolite of amitriptyline, providing similar efficacy without the additional burden of the parent compound's side effects. 5

Special Populations

Elderly Patients

• Nortriptyline is preferentially recommended in elderly patients due to its superior side effect profile. 5
• Maintenance therapy at 80-120 ng/ml plasma levels is associated with fewer residual depressive symptoms in elderly patients, though constipation may be more frequent at higher levels. 3

Cardiac Patients

• Nortriptyline can be used safely in cardiac transplant recipients with appropriate monitoring. 9
• Monitor for QRS interval prolongation and heart rate increases. 9
• Both nortriptyline and other TCAs are contraindicated in patients with recent MI, arrhythmias, heart block, or prolonged QTc syndrome. 5

Critical Monitoring Parameters

• Obtain baseline ECG before initiating therapy, particularly in patients with cardiac history. 8
• Monitor for orthostatic hypotension, especially during the first 1-2 weeks. 8
• Assess therapeutic response within 1-2 weeks, though full therapeutic trial requires 4-8 weeks. 8
• Obtain plasma levels if clinical response is inadequate or side effects emerge; therapeutic window is 50-150 ng/ml. 8, 4

Common Side Effects

• Anticholinergic effects: dry mouth, constipation, urinary retention, blurred vision (though less than amitriptyline). 5
• Cardiovascular: orthostatic hypotension, QTc prolongation, cardiac conduction abnormalities. 5
• Sedation and weight gain. 5
• Constipation is more frequent at higher plasma levels (80-120 ng/ml). 3

Duration of Treatment

For first-episode major depression, continue treatment for 4-9 months after satisfactory response; patients with 2 or more episodes may benefit from even longer duration therapy. 7