What is the typical starting dose of Amitriptyline (tricyclic antidepressant) for treating depression?

Amitriptyline Starting Dose for Depression

For depression treatment in adults, start amitriptyline at 75 mg daily in divided doses for outpatients, or begin with 50-100 mg at bedtime with gradual titration up to 150 mg daily as needed. 1

FDA-Approved Dosing for Depression

The FDA label provides clear guidance for initiating amitriptyline therapy:

• Outpatients: Begin with 75 mg daily in divided doses, which can be increased to 150 mg per day if necessary 1
• Alternative outpatient approach: Start with 50-100 mg at bedtime, increasing by 25-50 mg as needed to reach 150 mg daily 1
• Hospitalized patients: May start at 100 mg daily, gradually increasing to 200 mg daily if necessary 1
• Severely ill hospitalized patients: A small number may require up to 300 mg daily 1

Special Population Considerations

Adolescents and elderly patients require substantially lower starting doses due to increased risk of adverse effects:

• Start with 10 mg three times daily plus 20 mg at bedtime for those who cannot tolerate higher doses 1
• Elderly patients should receive approximately 50% of standard adult starting doses 2
• Plasma levels are generally higher in elderly patients for any given oral dose due to decreased hepatic metabolism and increased intestinal transit time 1

Critical Safety Warnings

Amitriptyline is considered potentially inappropriate in older adults according to the American Geriatric Society's Beers Criteria due to significant anticholinergic effects 2, 3:

• Common anticholinergic effects include dry mouth, constipation, urinary hesitancy, and sedation 2, 3
• Tertiary-amine TCAs like amitriptyline have more anticholinergic activity than secondary-amine alternatives (nortriptyline, desipramine) 2
• Obtain an ECG before initiating in patients with cardiac history; do not use if PR or QTc interval is prolonged 3
• Contraindicated in patients with ischemic heart disease, stroke, peripheral vascular disease, or uncontrolled hypertension 4

Titration and Monitoring

Increases should be made preferably in late afternoon and/or bedtime doses 1:

• A sedative effect may appear before antidepressant effect, but adequate therapeutic response may take up to 30 days 1
• The therapeutic plasma level range for amitriptyline plus its active metabolite nortriptyline is 80-200 ng/mL 3
• Monitor elderly patients carefully with quantitative serum levels as clinically appropriate 1

Maintenance Dosing

Once satisfactory improvement is achieved:

• Usual maintenance dose is 50-100 mg daily; some patients respond to 40 mg daily 1
• Total daily dose may be given as a single bedtime dose for convenience 1
• Continue maintenance therapy for at least 3 months to reduce relapse risk 1
• Clinical guidelines recommend 4-12 months of treatment after first depressive episode 2

Important Clinical Pitfall

Second-generation antidepressants (SSRIs, SNRIs) are generally considered first-line for depression due to superior tolerability 2. While amitriptyline shows statistically significant efficacy (odds ratio 1.12 for response vs other antidepressants), it has a significantly higher burden of side effects (odds ratio 0.63 favoring comparators) 5. The clinical significance of amitriptyline's modest efficacy advantage is unclear when weighed against its tolerability disadvantages 5.