Switching from Trazodone to Doxepin
When switching from trazodone to doxepin in adults, perform a direct switch without tapering trazodone, starting doxepin at a low dose (3-6 mg for insomnia, 25-50 mg for depression) on the same night you discontinue trazodone. Both medications are sedating antidepressants in the same therapeutic class with similar mechanisms, making cross-tapering unnecessary for most patients 1.
Rationale for Direct Switch
Both trazodone and doxepin are sedating low-dose antidepressants with no preferential recommendation for one over the other within this class 1. The American Academy of Sleep Medicine guidelines note that "no specific agent within this group is recommended as preferable to the others" and that selection should be guided by "specific side effect profile, cost, and pharmacokinetic profile" 1.
The key difference is anticholinergic burden: trazodone has little to no anticholinergic activity, while doxepin and amitriptyline have significant anticholinergic effects 1. This makes doxepin potentially more problematic in elderly patients or those with anticholinergic sensitivity.
Switching Protocol
For Insomnia (Low-Dose Use)
Stop trazodone (typically 25-100 mg) and start doxepin 3-6 mg the same evening 1. Low-dose doxepin is FDA-approved for insomnia at these doses.
Monitor for residual sedation the following day, as doxepin has a longer half-life than trazodone and may cause more morning drowsiness 1.
For Depression/Anxiety (Therapeutic Antidepressant Doses)
Stop trazodone (typically 150-300 mg) and start doxepin 25-50 mg the same evening 1.
Titrate doxepin upward by 25 mg every 3-7 days as needed, up to typical antidepressant doses of 75-150 mg daily 1.
For elderly or debilitated patients, start with lower doses (10-25 mg) and increase more gradually 1.
Important Caveats
When Tapering IS Necessary
Very slow taper of trazodone may be needed if the patient has been on high doses (>300 mg) for extended periods 2. One case series documented withdrawal symptoms despite gradual discontinuation, attributed to trazodone's effects on the serotonergic system and short half-life of trazodone and its active metabolite m-chlorophenylpiperazine 2. In such cases:
- Reduce trazodone by 25-50 mg every 3-7 days while simultaneously starting doxepin at low doses 2.
- The cross-taper should take 1-2 weeks maximum 2.
Monitoring Requirements
Assess for anticholinergic side effects within the first week: dry mouth, constipation, urinary retention, confusion (especially in elderly) 1.
Monitor for orthostatic hypotension in the first 2 weeks, as both medications can cause this, but the risk profile differs 3.
Evaluate sleep quality and daytime sedation after 3-7 days to determine if dose adjustment is needed 1, 4.
Contraindications and Warnings
Avoid doxepin in patients with narrow-angle glaucoma, urinary retention, or severe anticholinergic sensitivity 1.
Use extreme caution in elderly patients due to higher anticholinergic burden with doxepin compared to trazodone 1. Consider whether the switch is truly necessary, as trazodone may be preferable in this population.
Both medications should be used cautiously in patients with cardiovascular disease, though trazodone has been used successfully in patients with pre-existing cardiac conditions 3.
Dosing Considerations
Both medications can be given as single nighttime doses 4, 5. Studies demonstrate that once-daily evening dosing of trazodone (150-300 mg) provides equal antidepressant efficacy to divided dosing with better sleep and less daytime drowsiness 4. Similarly, doxepin can be administered once daily at bedtime 5.
The switch should be based on specific clinical factors 1:
- If the patient experienced inadequate efficacy with trazodone, doxepin may not provide additional benefit since they are in the same class
- If trazodone caused priapism (a known risk), doxepin is a reasonable alternative 3
- If the patient needs less anticholinergic activity, switching FROM doxepin TO trazodone would be more appropriate 1