What is the recommended treatment and dosage for major depressive disorder using Trazodone (antidepressant)?

Trazodone Treatment for Major Depressive Disorder

For major depressive disorder, trazodone is recommended at dosages of 150-300 mg/day, with administration preferably as a single bedtime dose to minimize side effects while maintaining efficacy. 1, 2

Dosing Recommendations

• Initial dosage should start at 25 mg per day and can be titrated up to a maximum of 200-400 mg per day in divided doses 3
• For optimal antidepressant efficacy, doses of 150-300 mg/day are typically required 1
• Single nighttime dosing is preferred over multiple daily dosing, as it:
  • Provides equal efficacy in relieving depression
  • Improves sleep quality
  • Reduces daytime drowsiness 2
• The recommended therapeutic plasma concentration range for trazodone is 650-1500 ng/mL 3

Monitoring and Response Timeline

• Begin assessing patient status, therapeutic response, and adverse effects within 1-2 weeks of treatment initiation 3
• If the patient does not have an adequate response within 6-8 weeks, treatment modification is strongly recommended 3
• Continue treatment for 4-9 months after a satisfactory response in patients with a first episode of major depressive disorder 3
• For patients who have had 2 or more episodes of depression, longer duration therapy (years to lifelong) may be beneficial 3

Pharmacological Profile and Mechanism

• Trazodone is a triazolopyridine serotonin receptor antagonist and reuptake inhibitor (SARI) antidepressant 1
• At low doses, trazodone acts as a serotonin antagonist, while at high doses it acts as a serotonin agonist 4
• It has minimal anticholinergic activity compared to older tricyclic antidepressants 5
• The half-life of trazodone is 3-9 hours, with an elimination half-life of 10-12 hours 2, 4

Side Effects and Safety Considerations

• Most common adverse effects include:
  • Somnolence/sedation (most common)
  • Headache
  • Dizziness
  • Dry mouth (xerostomia) 1, 6
• Serious but less common side effects to monitor:
  • Orthostatic hypotension (especially in patients with cardiovascular disease or older adults)
  • QT interval prolongation
  • Cardiac arrhythmias
  • Rare episodes of priapism 1, 5
• Trazodone is relatively safe in overdose compared to tricyclic antidepressants 5
• Use with caution in patients with premature ventricular contractions 3

Special Populations

• In elderly patients:
  • Maximum tolerated doses are 300-400 mg/day (lower than younger adults who may tolerate up to 600 mg/day)
  • Lower incidence of anticholinergic and cardiovascular effects compared to tricyclic antidepressants
  • Dosage should be reduced 5, 6

Clinical Advantages

• Particularly effective for patients with depression accompanied by insomnia 1, 2
• Low incidence of weight gain and sexual dysfunction compared to SSRIs 1, 6
• Can be used as monotherapy at 150-300 mg/day or in combination with other antidepressants at lower dosages 1
• Rapid onset of action for symptoms such as insomnia and psychomotor agitation 1

Drug Interactions

• Metabolized by CYP450 isoenzymes, primarily 2D6 and 3A4 6
• Dose adjustments may be necessary when administered with other drugs that influence these isoenzymes 6

Formulations

• Once-daily formulation (Trazodone CR) maintains effective blood levels for 24 hours while avoiding concentration peaks associated with side effects 1, 6
• This controlled-release form simplifies dosing and may reduce adverse effects 6