What are the precautions when prescribing tricyclic antidepressants (TCAs)?

Precautions When Prescribing Tricyclic Antidepressants (TCAs)

Exercise extreme caution with TCAs in patients with cardiovascular disease, particularly avoiding doses >100 mg/day due to increased risk of sudden cardiac death, and obtain an ECG before initiating therapy to screen for PR or QTc prolongation, which are contraindications to use. 1

Cardiovascular Precautions

• Cardiac conduction abnormalities are the most critical safety concern with TCAs, requiring ECG screening before initiation 1
• Doses exceeding 100 mg/day are associated with increased risk of sudden cardiac death based on large retrospective data 1
• If PR or QTc interval prolongation is present on ECG, TCAs should not be used 1
• Orthostatic hypotension is common and can lead to falls, particularly in elderly patients 1

Dosing Strategy to Minimize Adverse Effects

• Start at very low doses (10 mg/day in elderly patients, 25 mg/day in younger adults) and titrate slowly to reduce anticholinergic side effects 1
• Administer at bedtime to leverage sedative effects and minimize daytime impairment 1
• Prefer secondary-amine TCAs (nortriptyline or desipramine) over tertiary amines as they have fewer anticholinergic properties and are better tolerated 1
• Maximum recommended dose is typically 150 mg/day; if blood concentration of active medication and metabolite is <100 ng/mL, continue titration with caution 1

Anticholinergic Side Effects

• Common anticholinergic effects include dry mouth, constipation, urinary retention, and blurred vision 1, 2, 3
• Risk of paralytic ileus increases when TCAs are combined with other anticholinergic drugs (including antiparkinson agents) 2
• Close supervision required when administering with anticholinergic medications 2, 3

Drug Interactions Requiring Caution

• Cytochrome P450 2D6 inhibitors (cimetidine, fluoxetine, quinidine, SSRIs) can cause 8-fold increases in TCA plasma levels, leading to toxicity 2, 3
• When switching from fluoxetine to a TCA, wait at least 5 weeks due to fluoxetine's long half-life before initiating TCA therapy 2
• Avoid sympathomimetic amines (epinephrine, norepinephrine in decongestants and local anesthetics) as TCAs potentiate catecholamine effects 2
• TCAs enhance CNS depressant effects of alcohol; patients must be warned about this interaction 2, 3

Special Populations

Elderly Patients

• Use lower starting doses (10 mg/day) and slower titration in geriatric patients 1
• Confusional states are reported more frequently in elderly patients 3
• Higher plasma concentrations of active metabolites occur in elderly patients 3

Patients with Comorbidities

• Use with caution in significantly impaired renal or hepatic function; dosage adjustments may be necessary 2
• Both elevation and lowering of blood sugar levels reported; monitor diabetic patients closely 2, 3
• One case report documented significant hypoglycemia when nortriptyline was added to chlorpropamide therapy 3

Suicide Risk Management

• Dispense the least possible quantity of drug at any given time due to lethality in overdose 3
• Monitor closely for emergence of suicidal ideation, especially during treatment initiation and dose adjustments 2
• TCAs are potentially lethal in overdose, making this a critical safety consideration 2

Monitoring Requirements

• Perform leukocyte and differential blood counts if fever and sore throat develop during therapy 2
• Discontinue if pathological neutrophil depression occurs 2
• Consider therapeutic drug monitoring (TDM) when co-administering with P450 2D6 inhibitors to avoid toxicity 2

Preoperative Management

• Discontinue TCAs prior to elective surgery for as long as clinically feasible 2