What are the indications and side effects of Trazodone (antidepressant medication)?

Trazodone Indications and Side Effects

Trazodone is FDA-approved only for the treatment of major depressive disorder (MDD) in adults, but is commonly prescribed off-label for insomnia and as a mood stabilizer for agitation in various conditions. 1

Primary Indication

• Trazodone is indicated for the treatment of major depressive disorder (MDD) in adults 1
• Recommended dosage for depression is 150-300 mg/day, typically with a dose weighted at bedtime 2
• Efficacy is comparable to other antidepressants including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs) 3

Common Off-Label Uses

• Insomnia: Most frequent reason for trazodone prescription 4

  • Used at lower doses (25-100 mg) than for depression 5
  • Evidence for efficacy when used alone for chronic insomnia is relatively weak 5
  • Not recommended as first-line therapy for chronic insomnia according to the American Academy of Sleep Medicine 5

• Agitation in dementia and other psychiatric conditions:

  • Initial dosage: 25 mg per day; maximum: 200-400 mg per day in divided doses 5
  • Used as an alternative to antipsychotics for control of agitation 5

• Nightmares associated with PTSD:

  • Has shown efficacy in reducing nightmare frequency from 3.3 to 1.3 nights/week at mean dose of 212 mg/day 5

Side Effects

Common Side Effects

• Somnolence/sedation (most common) 3, 6
• Dizziness 1
• Headache 3
• Dry mouth (xerostomia) 3
• Nausea/vomiting (10-13%) 1
• Diarrhea (1-5%) 1
• Musculoskeletal aches/pains (3-6%) 1

Serious Adverse Effects

• Cardiovascular effects:

  • Orthostatic hypotension (especially in elderly or those with heart disease) 1, 3
  • QT interval prolongation and risk of torsade de pointes 1
  • Cardiac arrhythmias 1
  • Use with caution in patients with premature ventricular contractions 5

• Neurological effects:

  • Serotonin syndrome (when combined with other serotonergic medications) 1
  • Incoordination (2-5%) 1
  • Tremors (3-5%) 1
  • Potential for cognitive and motor impairment 1

• Urological effects:

  • Priapism (prolonged erection lasting >6 hours) - rare but serious adverse effect requiring immediate medical attention 1, 3

• Psychiatric effects:

  • Activation of mania or hypomania 1
  • Suicidal thoughts and behavior (boxed warning, especially in children, adolescents, and young adults) 1

• Other serious effects:

  • Hyponatremia 1
  • Increased risk of bleeding 1
  • Angle-closure glaucoma 1

Dosing Considerations

• For depression: 150-300 mg/day, typically administered as a single dose at bedtime 2
• For insomnia: 25-100 mg at bedtime 5
• For agitation in dementia: Starting at 25 mg/day, maximum 200-400 mg/day in divided doses 5
• Should be taken shortly after a meal or light snack to improve absorption and reduce side effects 1
• Elderly patients and those with hepatic impairment typically require lower doses 6

Special Precautions

• Avoid in combination with:

  • Alcohol and other CNS depressants (increased sedation) 1
  • MAO inhibitors (risk of serotonin syndrome) 1
  • Other serotonergic drugs (increased risk of serotonin syndrome) 1

• Use with caution in:

  • Elderly patients (increased risk of orthostatic hypotension) 3
  • Patients with cardiovascular disease 3
  • Patients with history of seizures 1
  • Patients taking medications that affect QT interval 1

Monitoring Recommendations

• Monitor for signs of suicidal ideation, especially when initiating therapy 1
• Monitor blood pressure for orthostatic hypotension, particularly in elderly patients 3
• Assess for cognitive and motor impairment, especially when driving or operating machinery 1
• Watch for signs of serotonin syndrome when combining with other serotonergic medications 1

Clinical Pearls

• Trazodone has minimal anticholinergic activity compared to tricyclic antidepressants, making it potentially better tolerated in elderly patients 5, 7
• Unlike many other antidepressants, trazodone is relatively safe in overdose 7
• When used for insomnia, tolerance and REM rebound do not typically occur upon discontinuation 2
• The sedating effects can be beneficial for patients with depression and comorbid insomnia 3
• Abrupt discontinuation may lead to withdrawal symptoms; tapering is recommended 1