What is the recommended dosage and treatment approach for an adult or geriatric patient with major depressive disorder, anxiety disorders, or insomnia, considering the use of Trazodone (antidepressant)?

Trazodone for Major Depressive Disorder: Dosing and Treatment Approach

Trazodone is NOT recommended for insomnia treatment, but remains an effective antidepressant for major depressive disorder at doses of 150-400 mg/day, particularly when depression presents with insomnia, anxiety, or when sexual dysfunction from SSRIs is problematic. 1, 2, 3

Critical Distinction: Depression vs. Primary Insomnia

The American Academy of Sleep Medicine explicitly recommends AGAINST using trazodone for primary insomnia (sleep onset or maintenance), as clinical trials showed only modest improvements in sleep parameters with no improvement in subjective sleep quality, and harms outweigh benefits. 1, 2

However, trazodone remains FDA-approved and guideline-supported for major depressive disorder, where it effectively treats the full spectrum of depressive symptoms including insomnia as a symptom of depression. 3, 4, 5

Dosing for Major Depressive Disorder

Initial Dosing

• Start at 150 mg/day in divided doses, taken shortly after a meal or light snack 3
• If drowsiness occurs, administer the major portion of the daily dose at bedtime or reduce the total dose 3

Dose Titration

• Increase by 50 mg/day every 3-4 days based on clinical response and tolerability 3
• Outpatients: Maximum 400 mg/day in divided doses 3
• Inpatients (more severely depressed): Up to 600 mg/day in divided doses 3

Therapeutic Range

• Effective antidepressant doses: 150-300 mg/day for monotherapy 5
• Lower doses (75-150 mg/day) may be used when combining with other antidepressants 5, 6

Treatment Algorithm for Depression

Step 1: Screen for Bipolar Disorder

Prior to initiating trazodone, screen for personal or family history of bipolar disorder, mania, or hypomania, as antidepressants can precipitate manic episodes. 3

Step 2: Assess Depression Phenotype

Trazodone is particularly indicated for:

• Depression with prominent insomnia (where insomnia is a symptom of depression, not primary insomnia) 5, 7
• Depression with anxiety and psychomotor agitation 5, 6
• Depression in patients who cannot tolerate SSRI side effects (sexual dysfunction, activation, insomnia) 4, 5
• Depression in elderly patients (comparable efficacy to tricyclics with better tolerability) 8

Step 3: Initiate Treatment

• Start 150 mg/day divided doses with food 3
• For elderly patients: Use lower starting doses and maximum doses of 300-400 mg/day 8, 6

Step 4: Monitor and Titrate

• Increase by 50 mg/day every 3-4 days as tolerated 3
• Monitor for drowsiness, dizziness, orthostatic hypotension (especially in elderly or those with cardiovascular disease) 4, 5
• Assess antidepressant response at 4-6 weeks 8

Step 5: Maintenance and Discontinuation

• Once adequate response achieved, gradually reduce to lowest effective maintenance dose 3
• When discontinuing, taper gradually rather than stopping abruptly to avoid withdrawal symptoms 3

Special Populations

Geriatric Patients

• Maximum tolerated doses: 300-400 mg/day (lower than younger adults) 8
• Monitor closely for orthostatic hypotension, falls, and cardiac effects 4, 5
• Trazodone shows comparable efficacy to tricyclics with notably lower anticholinergic and cardiovascular effects 8

Patients with Cardiovascular Disease

• Trazodone has been successfully used in patients with pre-existing cardiovascular disease 8
• Monitor for orthostatic hypotension, QT prolongation, and arrhythmias 4, 5
• Lower incidence of cardiovascular effects compared to tricyclic antidepressants 8

Anxiety Disorders

Limited evidence from older guidelines suggests trazodone may have some anxiolytic properties, though this is not its primary indication. 9

Drug Interactions and Contraindications

Absolute Contraindications

• Do not use within 14 days of MAOI antidepressants (either direction) 3

Dose Adjustments Required

• With strong CYP3A4 inhibitors: Consider reducing trazodone dose based on tolerability 3
• With strong CYP3A4 inducers: Consider increasing trazodone dose based on therapeutic response 3
• Hepatic impairment: Dose reduction required 2

Combination Therapy Cautions

• When combining with other serotonergic medications: Monitor for serotonin syndrome 10
• Avoid combining two sedating antidepressants (e.g., trazodone + mirtazapine) 1, 10
• With amiodarone: Use caution due to risk of elevated trazodone levels 10

Common Adverse Effects

Most Frequent

• Somnolence/sedation (most common) 4, 5
• Headache 4, 5
• Dizziness 4, 5
• Dry mouth 4, 5

Serious but Rare

• Orthostatic hypotension (particularly in elderly or those with heart disease) 4, 5
• Priapism (rare but requires immediate discontinuation) 2, 4
• QT prolongation and cardiac arrhythmias 4, 5
• Suicidal ideation (monitor closely, especially early in treatment) 4

Critical Pitfalls to Avoid

• Using trazodone as first-line treatment for primary insomnia (explicitly not recommended by guidelines) 1, 2
• Using subtherapeutic doses (25-50 mg) for depression (these doses are inadequate for antidepressant effect) 2, 3
• Combining multiple sedating agents without considering additive effects 1, 10
• Failing to screen for bipolar disorder before initiating 3
• Abrupt discontinuation rather than gradual taper 3
• Using in elderly patients without dose adjustment and close monitoring for falls 8, 5

Advantages Over Other Antidepressants

• Minimal sexual dysfunction (unlike SSRIs) 4, 5
• Improves sleep as part of depression treatment (unlike SSRIs which often worsen insomnia) 4, 5, 7
• Low risk of weight gain 5
• Minimal anticholinergic effects (compared to tricyclics) 4, 8
• Relatively safe in overdose (compared to tricyclics) 8
• Rapid onset of action 5