Tricyclic Antidepressants (TCAs)

Amitriptyline or nortriptyline for nerve pain. StatPearls calls amitriptyline the preferred tricyclic, but hedges: "in a 6 week randomized trial between amitriptyline and placebo involving 39 patients, there was no significant difference between the two."

Depression, insomnia, sialorrhea and pseudobulbar affect. "Amitriptyline is commonly used as it can also treat other symptoms such as insomnia, sialorrhea, and pseudobulbar affect."

Present on this page only as a class that has been displaced, and the ledger supports nothing more. The two sourced statements are comparative and negative: "SSRIs are recommended over monoamine oxidase inhibitors and tricyclic antidepressants" in panic disorder, and tricyclics and monoamine oxidase inhibitors are "less commonly used treatments for anxiety disorders" — described as older classes of antidepressants. No positive therapeutic role for a tricyclic in anxiety appears in the sources behind this page, so none is written here. The practical teaching is the positioning itself: when a student meets a tricyclic on an anxiety question, the expected answer is that an SSRI or SNRI comes first. The class page and the Depression page own the class facts, including the overdose-lethality profile that makes prescribing decisions in a population with elevated suicide risk consequential.

Effective but second-line, reserved largely for treatment-resistant depression — anticholinergic effects, orthostatic hypotension, a narrow therapeutic index, and above all lethality in overdose (QRS widening, ventricular arrhythmias; the highest death rate per million prescriptions among antidepressants, chiefly from deliberate overdose). In a patient population at suicide risk, that overdose lethality is exactly why SSRIs displaced them.

Low dose for persistent pain after an episode — "ongoing abdominal pain can be treated with a low to modest dose of a tricyclic antidepressant."

Avoided or reserved. In anorexia, TCAs "are less preferred due to concerns about cardiotoxicity, especially in malnourished patients". In bulimia, "Monoamine oxidase inhibitors and tricyclic antidepressants are reserved for resistant cases due to their lethality and potential side effects."

First-line for pain without major mood symptoms. StatPearls lists TCAs such as amitriptyline among first-line treatments; the dose "should be taken 1 to 3 hours before sleep." No doses on this page.

[PHN] "Tricyclic antidepressants such as amitriptyline and nortriptyline are also commonly used because of their analgesic properties; nortriptyline tends to be better tolerated." Caution in older adults: "The anticholinergic, antihistaminergic, and α-receptor–blocking adverse effects of TCAs must be considered because older adults are more susceptible."

Prevention: amitriptyline, especially with coexisting depression, anxiety or insomnia.

Clomipramine — effective, but second to SSRIs for long-term use. "Clomipramine, a tricyclic antidepressant (TCA), was the first drug to show efficacy in treating OCD." "Direct comparisons indicate equivalent efficacy between clomipramine and SSRIs. SSRIs are preferred for long-term treatment due to their superior safety profiles and tolerability than other antidepressants" (StatPearls). The label indication is "the treatment of obsessions and compulsions in patients with Obsessive-Compulsive Disorder (OCD)."

Second-line (StatPearls, relaying a 2022 review) — e.g., amitriptyline; NIDDK also names nortriptyline, desipramine and imipramine. NIDDK: "Doctors don’t recommend some medicines for older adults or for people with other health problems, such as heart disease." Like every DPN pain drug, TCAs relieve pain but "do not change the nerve damage."

A crisis trigger and a test interferer. Tricyclic antidepressants can trigger severe hypertension episodes and can falsely raise metanephrine results.

[Urge] NIDDK lists tricyclic antidepressants among medicines that relax the bladder for urgency incontinence; like anticholinergics and beta-3 agonists, "they can cause constipation."

Potent pain control via µ-opioid receptor agonism. Watch for respiratory depression; reverse with naloxone.

Potentiate GABA for anxiety, seizures, and sedation. Additive CNS depression — deadly with opioids.

First-line antidepressants that raise synaptic serotonin. Delayed onset; watch for serotonin syndrome and early suicidality.

Stabilize neuronal firing to prevent seizures. Many are narrow-therapeutic-index — level monitoring and rash vigilance are essential.

A widely used fever/pain reliever with no anti-inflammatory or platelet effect — but hepatotoxic in overdose.

Dopamine-blocking drugs for psychosis. Watch EPS, NMS, metabolic effects — boxed warning in elderly dementia.