Onset of Action for Trazodone
Trazodone demonstrates early antidepressant effects within 1 week of starting treatment, with significant improvement in depressive symptoms including insomnia occurring as early as day 7 at doses of 150 mg/day or higher. 1
Pharmacokinetic Timeline
- Trazodone is nearly completely absorbed after oral administration, with a redistribution half-life of approximately 1 hour and an elimination half-life of 10-12 hours. 2
- Peak plasma concentrations are reached within hours, though food delays absorption and reduces peak serum concentration without altering total drug exposure. 2
Clinical Onset of Therapeutic Effects
For Depression (Antidepressant Effect)
- Randomized controlled trials demonstrate statistically significant reduction in Hamilton Depression Rating Scale (HAM-D17) scores within 1 week of starting trazodone 150 mg/day compared to placebo or venlafaxine XR. 1
- In postmarketing studies, significant improvement from baseline depression scores occurred after 2 weeks of treatment, with normalization of scores by 6 weeks. 3
- The therapeutic antidepressant dosage range is 150-400 mg/day in divided doses, with lower doses (25-100 mg) used specifically for insomnia being subtherapeutic for depression. 4, 5
For Insomnia (Sedative Effect)
- The sedative effects of trazodone occur more rapidly than antidepressant effects, with drowsiness commonly reported as an immediate side effect. 6
- Significant early improvement in HAM-D17 sleep disturbance factor occurs by day 7 of treatment. 1
- Insomnia was identified as the most improved psychopathological symptom in clinical studies, though the American Academy of Sleep Medicine recommends against using trazodone for chronic insomnia due to insufficient evidence of benefit outweighing harms. 7, 3
Important Clinical Considerations
Dosing Context Matters
- For antidepressant effects, therapeutic doses of 150-300 mg/day are required, with maximum tolerated doses of 300-400 mg/day in elderly patients and up to 600 mg/day in younger patients. 6, 5
- Lower doses (25-100 mg) used off-label for insomnia provide immediate sedation but are inadequate for treating depression and lack robust evidence for efficacy even for sleep. 4, 8
Common Pitfall to Avoid
- Do not expect antidepressant effects from low doses (25-50 mg) prescribed for insomnia—these doses only provide sedation and are below the therapeutic threshold for mood improvement. 8
- The once-daily formulation maintains effective blood levels for 24 hours while avoiding concentration peaks associated with side effects, potentially improving tolerability and adherence. 5
Monitoring Timeline
- Assess for early improvement in sleep and anxiety symptoms within the first week of treatment at therapeutic doses. 1, 3
- Evaluate antidepressant response at 2 weeks, with full therapeutic effects typically evident by 6 weeks of continuous treatment. 3
- Most common immediate adverse effects include somnolence, headache, dizziness, and xerostomia, which should be monitored from the first dose. 5