What is a sample of a Tricyclic Antidepressant (TCA) for pain management?

Tricyclic Antidepressant (TCA) Examples for Pain Management

The most commonly used and extensively studied TCAs for pain management are amitriptyline, nortriptyline, desipramine, and imipramine, with amitriptyline being the most frequently prescribed and best-studied agent for neuropathic pain conditions. 1

Primary TCA Examples

Secondary Amine TCAs (Preferred)

• Nortriptyline: Starting dose 10-25 mg at bedtime, titrated by 25 mg every 3-7 days as tolerated to a maximum of 150 mg/day 1
• Desipramine: Starting dose 10-25 mg at bedtime, titrated by 25 mg every 3-7 days as tolerated to a maximum of 150 mg/day 1

Secondary amines (nortriptyline, desipramine) are better tolerated than tertiary amines due to fewer anticholinergic adverse effects such as sedation, dry mouth, and urinary hesitancy. 1

Tertiary Amine TCAs (More Efficacious but Less Tolerable)

• Amitriptyline: Starting dose 10-25 mg at bedtime, titrated every 3-5 days to 50-150 mg nightly 1, 2
• Imipramine: Similar dosing to amitriptyline 1

Tertiary amines (amitriptyline, imipramine) may be more efficacious but cause more anticholinergic side effects and should only be used if secondary amines are not available or effective. 1

Clinical Context and Selection

For Neuropathic Pain

Amitriptyline remains the most extensively studied TCA in post-herpetic neuralgia and diabetic neuropathy, achieving at least good or moderate response in up to two-thirds of patients with post-herpetic neuralgia and three-quarters with painful diabetic neuropathy. 3, 4

Nortriptyline and desipramine are preferred first-line choices due to superior tolerability profiles while maintaining comparable efficacy to amitriptyline. 1

For Cancer-Related Pain

TCAs are used as coanalgesics in combination with opioids for the neuropathic component of cancer pain, with analgesic effectiveness independent of antidepressant activity. 1

For Visceral Pain Syndromes

Amitriptyline is the most extensively studied and guideline-recommended TCA for functional gastrointestinal pain syndromes, including post-diverticulitis pain with visceral hypersensitivity. 2

Dosing Principles

The effective analgesic dose is often lower than that required to treat depression, and the onset of analgesic action is usually earlier than antidepressant effects. 1

An adequate trial requires 6-8 weeks, including at least 2 weeks at the maximum tolerated dosage. 1

Doses should be increased until analgesic effect is achieved, side effects become unmanageable, or the conventional maximal dose is reached. 1

Important Safety Considerations

Obtain a screening electrocardiogram for patients older than 40 years before initiating TCA therapy due to risks of arrhythmias, sinus tachycardia, and prolongation of conduction time. 1, 2

Amitriptyline should be avoided in patients aged 65 years or older due to strong anticholinergic effects associated with falls, cognitive decline, and increased mortality. 2

Prescribe TCAs with caution in patients with ischemic cardiac disease or ventricular conduction abnormalities, limiting dosages to less than 100 mg/day when possible. 1, 2

Utilization Patterns

In multidisciplinary pain centers, amitriptyline is the most commonly used TCA (58% of TCA prescriptions), followed by other agents, with most patients receiving low to intermediate doses (73% receive ≤50 mg amitriptyline equivalent). 5

Amitriptyline and doxepin appear more effective than other TCAs, though they also cause more side effects leading to dose limitation or discontinuation compared to imipramine, desipramine, and nortriptyline. 5