What is the use of Trazodone in treating depression and insomnia?

Trazodone Use in Depression and Insomnia

Trazodone is FDA-approved for treating major depressive disorder in adults but is not recommended for primary insomnia due to limited efficacy compared to placebo. 1, 2

Use in Depression

Trazodone is indicated for the treatment of major depressive disorder (MDD) in adults as confirmed by the FDA label 2. It belongs to the class of serotonin receptor antagonists and reuptake inhibitors (SARIs).

• Dosing for depression:

  • Should be taken shortly after a meal or light snack 2
  • Typical therapeutic dosage: 150-300 mg/day 3
  • Start with lower doses and titrate up based on response
  • Available in controlled-release formulation that maintains effective blood levels for 24 hours 3

• Efficacy in depression:

  • Comparable efficacy to other available antidepressants 3
  • Particularly effective for depression with concurrent insomnia symptoms 3, 4
  • Shows improvement in multiple depression symptoms including sadness and loss of drive 4

Use in Insomnia

Despite its widespread off-label use for insomnia, the evidence supporting trazodone for primary insomnia is limited.

• Not recommended for primary insomnia:

  • The American Academy of Sleep Medicine (AASM) explicitly recommends against using trazodone for primary insomnia 1
  • Shows limited efficacy with no improvement in sleep quality compared to placebo 1

• Secondary insomnia use:

  • May be beneficial for insomnia secondary to depression 5, 6
  • Often prescribed at lower doses (25-100 mg) for insomnia than for depression 5
  • Has been studied for insomnia related to depression, dementia, and in healthy individuals 5

Safety Considerations

• Common side effects:

  • Somnolence, headache, dizziness, and dry mouth 3
  • Drowsiness (most common side effect) 5
  • Side effects are dose-dependent 5

• Serious adverse effects:

  • Minimal anticholinergic activity 3
  • May cause orthostatic hypotension (especially in cardiovascular disease patients or older adults) 3
  • QT interval prolongation and cardiac arrhythmias (rare) 3
  • Priapism (rare) 3
  • Suicidal thoughts or actions (especially in children, teenagers, and young adults within first few months of treatment) 2

• Contraindications:

  • Should not be taken with MAOIs 2
  • Caution with triptans, other antidepressants, tramadol, NSAIDs, and warfarin due to drug interactions 2

Clinical Decision Algorithm

1. For Major Depressive Disorder:

   • Consider trazodone (150-300 mg/day) for patients with MDD, particularly when insomnia is a prominent symptom 3, 4
   • Monitor for efficacy within 2-4 weeks of initiation
   • Advantages include low incidence of weight gain and sexual dysfunction 3

2. For Insomnia:

   • Do not use for primary insomnia (per AASM guidelines) 1
   • Consider alternative recommended agents:
     • Zolpidem, zaleplon, or ramelteon for sleep onset insomnia
     • Doxepin (3-6mg), eszopiclone, temazepam, or suvorexant for sleep maintenance insomnia 1
   • For elderly patients, consider melatonin as first-line due to favorable safety profile 1

3. For Depression with Insomnia:

   • Trazodone may be particularly beneficial when depression is accompanied by insomnia 6
   • Consider controlled-release formulation for once-daily dosing 4
   • Monitor for improvement in both depression and sleep symptoms

Important Caveats

• The evidence for trazodone in treating primary insomnia is limited, with most studies being small and conducted in depressed populations 7
• High discontinuation rates due to side effects such as sedation, dizziness, and psychomotor impairment are concerning, especially in elderly patients 7
• Non-pharmacological approaches (sleep hygiene education, CBT-I, regular sleep schedule) should be considered as first-line treatments for insomnia 1
• Always assess for suicidal thoughts, especially when initiating treatment or changing doses 2