When is Amitriptyline (tricyclic antidepressant) prescribed for depression?

When to Prescribe Amitriptyline for Depression

Amitriptyline should primarily be prescribed for severe depression, particularly in hospitalized patients, as it shows superior efficacy compared to SSRIs in this population due to its dual action on both serotonin and norepinephrine neurotransmitters. 1

Primary Indications for Amitriptyline in Depression

• Amitriptyline is most effective in severe depression, particularly in hospitalized patients, where it demonstrates a significant efficacy advantage over SSRIs 1
• It is particularly effective when prescribed as a dual-acting tertiary amine tricyclic antidepressant (inhibiting both serotonin and norepinephrine reuptake) for patients with severe depressive symptoms 1
• For outpatients with mild to moderate depression, SSRIs are generally preferred over amitriptyline due to better tolerability and similar efficacy in this population 2

Dosing Considerations

• For outpatients, initiate at 75 mg daily in divided doses, which can be increased to a maximum of 150 mg daily if necessary 3
• An alternative approach for outpatients is to begin with 50-100 mg at bedtime, which can be increased by 25-50 mg as needed to a total of 150 mg daily 3
• Hospitalized patients may require 100 mg daily initially, which can be increased gradually to 200 mg daily if necessary, with some patients needing up to 300 mg daily 3
• Lower doses are recommended for adolescent and elderly patients: 10 mg three times daily with 20 mg at bedtime may be sufficient 3
• Maintenance dosage is typically 50-100 mg daily, with some patients requiring only 40 mg daily 3

Special Populations

• Amitriptyline is not recommended for children under 12 years of age due to lack of experience in this population 3
• In adolescents with depressive episodes, fluoxetine (not amitriptyline or other tricyclics) may be considered in non-specialist settings with close monitoring for suicidal ideation 1
• Elderly patients require lower starting doses due to decreased drug clearance, increased risk of side effects, and potential drug interactions 4, 3
• Plasma levels are generally higher in elderly patients for a given oral dose due to increased intestinal transit time and decreased hepatic metabolism 3

Contraindications and Precautions

• Amitriptyline should be used with caution in patients with cardiovascular disorders as it can produce arrhythmias, sinus tachycardia, and prolongation of conduction time 3
• It should be used cautiously in patients with a history of seizures, urinary retention, angle-closure glaucoma, or increased intraocular pressure 3
• Amitriptyline may block the antihypertensive action of guanethidine or similar compounds 3
• It should be used with caution in patients with impaired liver function 3
• Schizophrenic patients may develop increased psychotic symptoms, and patients with paranoid symptoms may experience exacerbation 3
• Patients with manic-depressive illness may experience a shift to mania or hypomania 3

Monitoring and Side Effects

• Patients should be monitored for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of treatment or during dose adjustments 3
• Common side effects include anticholinergic effects, tachycardia, dizziness, nervousness, sedation, tremor, dyspepsia, sexual dysfunction, and weight gain 5
• More patients withdraw from amitriptyline treatment due to side effects compared to placebo (OR 4.15,95% CI 2.71 to 6.35) 5
• Amitriptyline may impair mental and/or physical abilities required for performing hazardous tasks 3

Efficacy Considerations

• Amitriptyline is significantly more effective than placebo in achieving acute response (OR 2.67,95% CI 2.21 to 3.23) 5
• Higher severity of depression at baseline is associated with greater superiority of amitriptyline over placebo 5
• Amitriptyline may cause memory impairment despite alleviation of depression, particularly after 4 weeks of treatment 6

Clinical Algorithm for Amitriptyline Use in Depression

1. First-line use: Consider amitriptyline as first-line for hospitalized patients with severe depression 1, 2
2. Second-line use: Consider amitriptyline for outpatients who have failed SSRI therapy or have specific indications for a tricyclic antidepressant 2
3. Avoid in: Patients with significant cardiovascular disease, narrow-angle glaucoma, urinary retention, or significant risk factors for these conditions 3, 7
4. Monitor closely: All patients for side effects, particularly anticholinergic effects, and for suicidal ideation, especially in the first few weeks of treatment 3, 5