What are the uses, dosing, and side effects of tricyclic antidepressants (TCAs)?

Tricyclic Antidepressants: Uses, Dosing, and Side Effects

Tricyclic antidepressants (TCAs) are effective first-line treatments for neuropathic pain and second-line treatments for depression, with secondary amine TCAs (nortriptyline, desipramine) being preferred over tertiary amine TCAs (amitriptyline, imipramine) due to their better side effect profile. 1

Primary Uses

• Neuropathic Pain: TCAs are first-line treatments for multiple types of neuropathic pain, with established efficacy in placebo-controlled randomized controlled trials 1
• Depression: TCAs are second-line treatments for depression after SSRIs/SNRIs due to their side effect profile 1
• Irritable Bowel Syndrome: TCAs are suggested for IBS treatment, particularly for abdominal pain relief 1
• Chronic Pain Conditions: Used for fibromyalgia, headache, migraine, and pelvic pain 1, 2

Dosing Guidelines

For Neuropathic Pain:

• Starting Dose: Begin with low doses (10-25mg) administered at bedtime 1
• Titration: Slowly titrate to higher dosages with careful monitoring 1
• Target Dose:
  • For analgesia: Often effective at lower doses (25-75mg/day) than those used for depression 1, 3
  • For depression: May require higher doses (150-300mg/day) 1, 4
• Duration: Adequate trial requires 6-8 weeks, including 2 weeks at the highest tolerated dose 1

For Elderly Patients:

• Start at lower doses (approximately 50% of adult starting dose) 1, 5
• Observe closely for side effects 5
• Limit doses to less than 100mg/day when possible 1, 3

Side Effects

Anticholinergic Effects:

• Common symptoms: Dry mouth, blurred vision, constipation, urinary retention 1, 5
• Severity: More pronounced with tertiary amine TCAs (amitriptyline, imipramine) than secondary amine TCAs (nortriptyline, desipramine) 3, 5
• Management: Can be reduced by starting with low doses at bedtime and slow titration 1

Cardiovascular Effects:

• ECG changes: Prolongation of PR and QT intervals, bundle branch block patterns 5, 6
• Arrhythmias: Sinus tachycardia, supraventricular or ventricular tachycardias 5, 6
• Risk factors: Higher doses (>100mg/day), pre-existing cardiac disease 1, 3
• Precaution: Obtain screening ECG for patients older than 40 years before starting treatment 1

Central Nervous System Effects:

• Sedation, cognitive impairment, psychomotor slowing 5
• Confusion and delirium, especially in elderly patients 5
• Increased risk of falls in elderly patients 5

Other Concerns:

• Overdose risk: TCAs are highly toxic in overdose compared to newer antidepressants 6
• Drug interactions: Significant interactions with SSRIs, cimetidine, and other CYP2D6 inhibitors 5
• Discontinuation: Taper doses when stopping to avoid withdrawal syndrome 1

Clinical Pearls

• TCA Selection: Secondary amine TCAs (nortriptyline, desipramine) are preferred in elderly patients and those with cardiovascular disease due to fewer anticholinergic and cardiac effects 1, 3
• Monitoring: For patients with cardiac risk factors, obtain baseline ECG and monitor for cardiovascular effects 1
• Efficacy for Pain: Analgesic effects of TCAs are independent of their antidepressant effects and have been established in non-depressed patients 1
• Cost-effectiveness: TCAs are inexpensive compared to newer agents and can be administered once daily 1
• Contraindications: Use with caution in patients with ischemic cardiac disease, ventricular conduction abnormalities, angle-closure glaucoma, or urinary retention 1, 5

Special Populations

• Elderly: More sensitive to anticholinergic side effects; start at lower doses and monitor closely 5
• Pediatric: Safety and effectiveness not established; not recommended for patients under 12 years 5
• Pregnancy: Category C; use only if potential benefit justifies potential risk to fetus 5
• Nursing mothers: Excreted in breast milk; consider discontinuing nursing or the drug 5