Recommended Dosage of Amitriptyline for Depression
The recommended initial dose of amitriptyline for treating depression in adults is 75 mg per day in divided doses, which can be increased to a maximum of 150-200 mg per day based on clinical response and tolerability. 1
Dosing Guidelines
Initial Dosing
- Outpatients: 75 mg daily in divided doses 1
- Hospitalized patients: May require 100 mg daily initially, which can be increased gradually to 200 mg daily if necessary 1
- Alternative initiation method: Begin with 50-100 mg at bedtime, increasing by 25-50 mg as needed to a total of 150 mg daily 1
- Elderly and adolescents: Lower dosages recommended - 10 mg three times daily with 20 mg at bedtime 1
Titration
- Increase dose gradually while monitoring clinical response and side effects
- Increases preferably made in late afternoon and/or bedtime doses 1
- Therapeutic effect may take up to 30 days to develop, though sedative effects may appear earlier 1
Maintenance Dosing
- Usual maintenance dose: 50-100 mg daily 1
- In some patients, 40 mg daily may be sufficient 1
- For maintenance therapy, the total daily dose may be given as a single bedtime dose 1
- Maintenance therapy should continue for at least 3 months to reduce relapse risk 1
Special Populations
Elderly Patients
- Lower starting doses (10 mg three times daily with 20 mg at bedtime) 1
- Elderly patients have increased intestinal transit time and decreased hepatic metabolism, resulting in higher plasma levels for a given dose 1
- Should be monitored carefully with serum levels obtained as clinically appropriate 1
Adolescents
- Lower dosages similar to elderly patients 1
- 10 mg three times daily with 20 mg at bedtime may be sufficient 1
Children
- Not recommended for patients under 12 years of age due to lack of experience 1
Monitoring and Adjustments
- Adjust dosage according to clinical response rather than plasma levels 1
- Consider ECG monitoring in patients with cardiovascular risk factors 2
- Monitor for side effects including anticholinergic effects (dry mouth, constipation, urinary retention), sedation, and cardiovascular effects 2, 3
Efficacy Considerations
- Amitriptyline is considered one of the reference compounds for pharmacological treatment of depression 4
- Studies show it is at least as efficacious as other tricyclics or newer compounds 4
- More effective than control antidepressants in inpatient settings 4
- Comparable efficacy to sertraline in outpatient settings 5
Side Effect Profile
- Higher burden of side effects compared to selective serotonin reuptake inhibitors (SSRIs) 4
- Common side effects include sedation, dry mouth, blurred vision, constipation, and weight gain 2
- May cause cardiovascular effects including increased heart rate and reduced heart rate variability 3
- Anticholinergic effects are more likely with amitriptyline compared to secondary amines like nortriptyline 2
Clinical Pearls
- A sedative effect may appear before the antidepressant effect 1
- Tertiary-amine TCAs like amitriptyline have significant anticholinergic effects and are considered potentially inappropriate in geriatric patients according to Beers Criteria 2
- Secondary-amine TCAs (e.g., nortriptyline) may be safer alternatives for elderly patients due to lower anticholinergic effects 2
- For patients with depression and insomnia, the sedative properties of amitriptyline may be beneficial when dosed at bedtime 2
Common Pitfalls to Avoid
- Starting with too high a dose, especially in elderly patients
- Expecting immediate therapeutic effects (may take up to 30 days)
- Discontinuing too early (maintenance therapy should continue at least 3 months)
- Not monitoring for cardiovascular effects, especially in at-risk patients
- Not considering drug interactions with other medications
Amitriptyline remains an effective option for treating depression, particularly for inpatients and those who may benefit from its sedative properties, though careful monitoring for side effects is essential.