When should amitriptyline (tricyclic antidepressant) be given for depression?

When to Use Amitriptyline for Depression

Amitriptyline should not be used as a first-line treatment for depression but may be considered as a second or third-line option specifically for inpatients with severe depression who have not responded to other antidepressants. 1, 2, 3

Patient Selection Considerations

Appropriate Candidates

• Inpatients with severe depression: Amitriptyline shows greater efficacy compared to other antidepressants specifically in hospitalized patients 3
• Adults with treatment-resistant depression: When first-line treatments have failed 2
• Patients with severe depression: Higher baseline severity is associated with greater superiority of amitriptyline over placebo 2

Inappropriate Candidates

• Children and adolescents: Amitriptyline is not recommended for patients under 12 years of age due to lack of experience in this population 4
• Adolescents with depressive episodes: Tricyclic antidepressants should not be used; fluoxetine may be considered instead 1
• Outpatients with mild to moderate depression: No significant advantage over SSRIs but more side effects 3

Dosing Recommendations

Adult Dosing

• Outpatients: Start with 75 mg/day in divided doses, may increase to 150 mg/day if necessary 4
• Inpatients: May require 100 mg/day initially, can be increased gradually to 200 mg/day if necessary; some may need up to 300 mg/day 4
• Maintenance: 50-100 mg/day (some patients may respond to 40 mg/day) 4

Special Populations

• Elderly and adolescent patients: Lower dosages recommended - 10 mg three times daily with 20 mg at bedtime 4
• Maintenance therapy: Total daily dosage may be given as a single dose at bedtime 4

Monitoring and Duration

• Therapeutic effect: May take up to 30 days to develop 4
• Maintenance duration: Continue therapy for at least 3 months after satisfactory response to reduce relapse risk 4, 5
• Side effect monitoring: Regular monitoring for anticholinergic effects, tachycardia, dizziness, sedation, weight gain, and sexual dysfunction 1
• Suicide risk: Close monitoring required, especially early in treatment 4

Advantages and Disadvantages

Advantages

• More effective than placebo for depression (OR 2.67) 2
• May be more effective than other antidepressants for inpatients (OR 1.22) 3
• Slightly higher overall response rates compared to other antidepressants 6

Disadvantages

• Higher rate of side effects compared to SSRIs and other newer antidepressants 1, 7
• Risk of QT prolongation, particularly concerning in elderly patients 1
• More withdrawals due to side effects (OR 4.15 compared to placebo) 2
• Anticholinergic effects, sedation, and weight gain are common 1, 2

Important Precautions

• Suicide risk: Increased monitoring needed, especially during initial treatment and dose changes 4
• Cardiac effects: Risk of QT prolongation, particularly with amitriptyline 1
• Drug interactions: Careful evaluation needed, especially in elderly patients taking multiple medications 8
• Pregnancy and breastfeeding: Consider alternatives with better safety profiles 1
• Psychiatric comorbidities: May exacerbate psychosis or trigger mania in patients with bipolar disorder 4

Alternative Treatments to Consider First

• SSRIs: Better tolerated than amitriptyline, especially for outpatients 1, 3
• SNRIs: May provide additional benefits for patients with comorbid pain disorders 1
• CBT: Effective first-line treatment for moderate depression, with similar efficacy to antidepressants in the short term 8

Amitriptyline remains an effective antidepressant but should be reserved for specific situations where its benefits outweigh its considerable side effect profile, particularly for hospitalized patients with severe depression who haven't responded to newer, better-tolerated medications.