Educational use only. Drug cards are AI-assisted study material for NCLEX preparation.
Tricyclic antidepressants (amitriptyline, nortriptyline, imipramine, clomipramine, doxepin)
Mechanism of action
Block reuptake of serotonin and norepinephrine; also strongly antagonize muscarinic, histaminergic, and alpha-1 adrenergic receptors — the source of most of their side effects and toxicity. Largely supplanted by SSRIs/SNRIs as first-line antidepressants but still used for neuropathic pain, migraine prophylaxis, chronic insomnia, OCD (clomipramine), and treatment-resistant depression.
Adverse effects
Life-threatening / NCLEX-tested
- Cardiotoxicity in overdose — life-threatening; QRS widening, arrhythmias, seizures; very narrow therapeutic margin in overdose (~1 week's supply can be lethal)
- Severe orthostatic hypotension and syncope
- Seizures, especially in overdose or at high doses
- Anticholinergic toxicity (urinary retention, ileus, hyperthermia, delirium)
- Suicidality risk in patients < 25 (boxed warning)
- Serotonin syndrome with serotonergic agents
- Severe withdrawal if abruptly stopped
Side effects
Common — what to teach
- Anticholinergic — dry mouth, blurred vision, urinary hesitancy, constipation
- Sedation (especially amitriptyline, doxepin)
- Weight gain
- Sexual dysfunction
- Mild tremor
- Excessive sweating
Food & drug interactions
MAOIs are an ABSOLUTE contraindication — wait 14 days. Other serotonergic agents compound serotonin syndrome risk. Anticholinergic stacking (antihistamines, antipsychotics, oxybutynin) → toxicity. CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion) raise levels. Class IA/III antiarrhythmics compound QT/QRS effects. Alcohol amplifies sedation and cardiotoxicity.
Nursing implications
Assessment, monitoring, patient teaching
- Counsel that mood effect takes 4–6 weeks; sedation often appears immediately and may help anxiety/sleep
- Suicide risk: limit dispensed quantity early in treatment; involve family/safety plan
- Counsel on slow position changes — orthostasis is real, especially in older adults
- Anticholinergic side effects: sugarless gum, hydration, fiber/laxatives for constipation, frequent eye drops; monitor for urinary retention and ileus
- Take at bedtime to leverage sedation and reduce daytime drowsiness
- Teach about serotonin syndrome warning signs
- Avoid abrupt discontinuation — taper over weeks
- Baseline ECG in older adults and patients with cardiac history; QTc and QRS surveillance
When to hold / contraindications
- MAOI within 14 days
- Recent acute MI or known severe arrhythmia / heart block
- Suspected overdose — TCA overdose is a medical emergency (consider sodium bicarbonate per protocol)
- Severe orthostatic hypotension or recent syncope
- Acute closed-angle glaucoma, severe BPH with retention, paralytic ileus (anticholinergic burden)
- Active suicidal crisis without safety plan and team involvement
Memory anchor
TCAs end in "-iptyline" or "-ipramine." Anticholinergic + cardiotoxic in overdose. Bedtime dosing leverages sedation. "One week's supply can kill" — limit dispensing early.
Practice Tricyclic questions
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