What is the recommended dosing regimen for Tricyclic Antidepressants (TCAs)?

Tricyclic Antidepressant (TCA) Dosing Regimen

Start TCAs at 10 mg at bedtime and titrate by 10 mg weekly or biweekly to a target dose of 30-50 mg daily for chronic pain conditions, or 25-75 mg daily for depression, with careful monitoring for cardiovascular and anticholinergic side effects. 1

Starting Dose

• Initiate at 10 mg at bedtime for chronic gastrointestinal pain, neuropathic pain, and most pain-related conditions 1
• For depression in outpatients, start at 25 mg daily (amitriptyline or nortriptyline) 1
• For hospitalized depression patients, begin at 100 mg daily in divided doses 2
• In elderly patients and adolescents, use 10 mg daily initially, which may not need to exceed 40-100 mg daily 1

Titration Schedule

• Increase by 10 mg per week or per fortnight according to symptom response and tolerability for pain conditions 1
• For depression, increase by 25 mg every 3-7 days as tolerated 1
• For neuropathic pain, titrate to 75 mg daily as the standard target dose 1

Target and Maximum Doses

For Chronic Pain (IBS, Functional GI Disorders, Neuropathic Pain):

• Target dose: 30-50 mg at night 1
• This lower dose range is effective for pain modulation through norepinephrine effects 1

For Depression:

• Outpatients: 75-150 mg daily 2
• Hospitalized patients: 200-300 mg daily (may increase to 250-300 mg if no response after 2 weeks) 2
• Maximum recommended: 150 mg daily for most patients 1
• Evidence supports that 75-100 mg daily is often as effective as higher doses with fewer side effects 3, 4

For Neuropathic Pain:

• Target: 25-75 mg daily (amitriptyline or imipramine) 1
• Do not exceed 100 mg daily due to increased risk of sudden cardiac death at higher doses 1

Critical Safety Considerations

Cardiovascular Monitoring:

• Obtain baseline ECG in patients over 40 years before initiating therapy 1
• Avoid or use extreme caution in patients with ischemic heart disease or ventricular conduction abnormalities 1
• Do not exceed 100 mg daily in patients with cardiovascular disease due to arrhythmia and sudden death risk 1
• Check for PR or QTc prolongation; if present, do not use TCAs 1

Common Side Effects Requiring Monitoring:

• Anticholinergic effects: dry mouth, dry eyes, constipation, sedation 1
• Cardiovascular: orthostatic hypotension, tachycardia, conduction delays 1
• These effects are dose-dependent and more common with tertiary amines (amitriptyline, imipramine) than secondary amines (nortriptyline, desipramine) 1

Agent Selection

Secondary Amines (Preferred for Better Tolerability):

• Nortriptyline or desipramine have fewer anticholinergic side effects than tertiary amines 1
• Nortriptyline: 10 mg at bedtime, titrate to maximum 40 mg daily; has therapeutic blood level window of 50-150 ng/mL 1
• Desipramine: 10-25 mg in morning, maximum 150 mg daily; tends to be activating 1

Tertiary Amines:

• Amitriptyline: most commonly used for pain conditions 1
• Imipramine: 25-75 mg daily for pain; up to 300 mg daily for hospitalized depression patients 1, 2

Duration of Adequate Trial

• Minimum 6-8 weeks including at least 2 weeks at maximum tolerated dose to assess efficacy 1
• For pain conditions, reassess after reaching target dose of 30-50 mg 1

Key Clinical Pitfalls

• Starting too high: Always start at 10 mg in elderly, pain patients, or those with cardiovascular risk 1
• Titrating too quickly: Rapid escalation increases dropout due to side effects 1
• Exceeding 100 mg without ECG monitoring: Significantly increases cardiac risk 1
• Not counseling patients: Explain that TCAs are used for pain modulation, not depression, to improve adherence 1
• Ignoring drug interactions: TCAs have multiple cytochrome P450 interactions 1