When is trazodone (antidepressant) recommended for use in patients with major depressive disorder (MDD) or insomnia, particularly in the geriatric population?

When to Use Trazodone

Trazodone is FDA-approved exclusively for major depressive disorder (MDD) in adults, where it demonstrates comparable efficacy to SSRIs and other second-generation antidepressants, but should NOT be used as first-line treatment for primary insomnia without depression. 1, 2

Primary Indication: Major Depressive Disorder

• Trazodone is indicated for treating MDD in adults as monotherapy at doses of 150-300 mg/day. 1, 3
• The American College of Physicians recommends selecting second-generation antidepressants (including trazodone) based on adverse effect profiles, cost, and patient preferences, as all show similar efficacy for acute MDD treatment. 2
• Trazodone demonstrates equivalent antidepressant efficacy compared to SSRIs (fluoxetine, paroxetine, sertraline), tricyclics, and SNRIs in head-to-head trials. 2, 4

Specific Clinical Scenarios Where Trazodone Is Particularly Useful

MDD with Prominent Insomnia

• When depression presents with insomnia as a major symptom, trazodone becomes a preferred choice among antidepressants because it treats both conditions simultaneously. 5, 6
• Trazodone improves sleep architecture while treating the underlying depression, unlike SSRIs which often worsen insomnia. 6, 3
• Full antidepressant dosing (150-300 mg/day) is required when treating MDD with insomnia—low doses alone are insufficient for depression. 5

MDD with Anxiety or Psychomotor Agitation

• Trazodone shows comparable efficacy to other second-generation antidepressants for treating anxiety symptoms accompanying MDD. 2
• The low liability for activating side effects and rapid onset of action make trazodone useful for patients with psychomotor agitation. 3

Elderly Patients with Depression

• Trazodone can be used in geriatric patients with MDD, though caution is warranted due to increased risk of orthostatic hypotension and hyponatremia. 1, 7
• Maximum tolerated doses in elderly patients are typically 300-400 mg/day compared to 600 mg/day in younger adults. 7
• Monitor closely for orthostatic hypotension, especially during initiation and dose increases in elderly patients. 7, 3

When Trazodone Should NOT Be Used as First-Line

Primary Chronic Insomnia Without Depression

• The American Academy of Sleep Medicine explicitly recommends AGAINST using trazodone as first-line treatment for primary insomnia. 2
• For primary insomnia, the treatment hierarchy is: (1) benzodiazepine receptor agonists or ramelteon first, (2) alternate BzRA if initial agent fails, (3) then sedating antidepressants like trazodone as third-line. 2, 5
• Evidence for trazodone's efficacy when used alone for insomnia is relatively weak compared to FDA-approved hypnotics. 2

Insomnia Moves Trazodone Up the Algorithm Only When:

• Comorbid depression accompanies the insomnia, making trazodone appropriate as it addresses both conditions. 5
• Other treatments (BzRAs, ramelteon) have failed AND depression is present. 2

Combination Therapy Strategies

Adjunctive Low-Dose Trazodone (50-100 mg)

• Low-dose trazodone (50-100 mg at bedtime) can be added to SSRIs or other antidepressants to counteract SSRI-induced insomnia, anxiety, or sexual dysfunction. 5, 8
• This low-dose adjunctive use does NOT constitute adequate treatment for MDD itself—the primary antidepressant must be at full therapeutic dose. 2, 5
• Trazodone's 5-HT2A receptor antagonism helps prevent initial and long-term SSRI side effects. 8

Treatment Algorithm for Depression

1. Assess for MDD diagnosis and evaluate accompanying symptoms (insomnia, anxiety, psychomotor changes). 2
2. If MDD with prominent insomnia: Consider trazodone as first-line antidepressant at 150-300 mg/day. 5, 6
3. If MDD without insomnia: Select any second-generation antidepressant based on side effect profile, cost, and patient preference—trazodone has no efficacy advantage over alternatives. 2
4. Monitor response within 1-2 weeks of initiation; modify treatment if inadequate response by 6-8 weeks. 2, 5
5. Continue treatment 4-9 months after satisfactory response for first episode; longer duration for recurrent episodes. 2

Key Advantages Over Other Antidepressants

• Minimal anticholinergic activity compared to tricyclic antidepressants. 2
• Does not cause the insomnia, anxiety, or sexual dysfunction commonly seen with SSRIs. 4, 3
• Low incidence of weight gain and sexual dysfunction may improve adherence. 3
• Relatively safe in overdose compared to tricyclic antidepressants. 7

Critical Safety Considerations and Monitoring

Common Adverse Effects

• Somnolence/sedation, headache, dizziness, and dry mouth are most frequent. 4, 3
• Drowsiness is the most commonly reported side effect and may limit daytime dosing. 7

Serious but Rare Adverse Effects

• Orthostatic hypotension, particularly in elderly patients or those with cardiovascular disease—monitor blood pressure during initiation. 1, 7, 3
• QT interval prolongation and cardiac arrhythmias—use caution in patients with cardiac disease. 4, 3
• Priapism (rare but requires immediate medical attention). 4, 7
• Increased risk of suicidal thoughts in pediatric patients (not approved for use in children). 1

Special Populations Requiring Caution

• Renal impairment: Use with caution; trazodone has not been formally studied in this population. 1
• Hepatic impairment: Use with caution; no formal studies available. 1
• Pregnancy: Consider risk-benefit ratio; untreated depression carries risks, but limited human data available. 1
• Elderly: Increased risk of hyponatremia and orthostatic hypotension; start with lower doses. 1, 7

Common Pitfalls to Avoid

• Do not use low-dose trazodone (50-100 mg) as monotherapy for MDD—this is inadequate for treating depression and only appropriate as adjunctive sleep aid. 2, 5
• Do not prescribe trazodone as first-line for primary insomnia without depression—this contradicts current guidelines. 2
• Do not assume trazodone is superior to other antidepressants for MDD without insomnia—efficacy is equivalent across second-generation agents. 2
• Do not overlook cardiovascular monitoring in elderly patients—orthostatic hypotension risk is significant. 7, 3