Can Trazodone Be Added for Sleep in Patients on Cymbalta and Wellbutrin?
Yes, trazodone can be used as needed for sleep in patients taking duloxetine (Cymbalta) and bupropion (Wellbutrin), but this combination requires careful monitoring for serotonin syndrome and should be introduced gradually at low doses (25 mg at bedtime). 1, 2
Key Safety Considerations
Serotonin Syndrome Risk
- The combination of duloxetine (an SNRI), bupropion, and trazodone increases the theoretical risk of serotonin syndrome, though this risk is relatively low at typical sleep doses of trazodone 2
- The FDA label explicitly warns about using trazodone with SNRIs and other serotonergic medications 2
- Medications should be introduced gradually, not rapidly titrated, to minimize serotonin syndrome risk 1
- Monitor for symptoms including agitation, hallucinations, coordination problems, fast heartbeat, tight muscles, sweating, fever, nausea, vomiting, and diarrhea 2
Practical Dosing Strategy
- Start with trazodone 25 mg at bedtime, which is the typical low dose used for sleep 1
- This dose is below the 50 mg dose studied in insomnia trials and well below antidepressant dosing ranges 3
- Administer trazodone shortly after a meal or light snack as recommended 2
- Ensure bupropion's second dose is given before 3 PM to minimize its contribution to insomnia 1
Important Caveats About Trazodone for Insomnia
Evidence Limitations
- The American Academy of Sleep Medicine actually recommends against using trazodone for insomnia treatment based on trials showing modest benefits that don't outweigh potential harms 3
- Clinical trials of 50 mg trazodone showed no improvement in subjective sleep quality compared to placebo 3
- Trazodone is considered a third-line agent, appropriate only after FDA-approved sleep medications and cognitive behavioral therapy for insomnia (CBT-I) have been tried or are inappropriate 3
When This Combination Makes Clinical Sense
- Despite guideline recommendations against trazodone, it remains commonly prescribed (second most common sleep medication in the U.S.) 4
- Real-world data shows trazodone is prescribed concomitantly with SSRIs/SNRIs in 27% of cases and with bupropion in 23% of cases 5
- This combination may be particularly appropriate when the patient has comorbid depression or anxiety, as trazodone can augment antidepressant effects at higher doses 3
Monitoring and Side Effects
Common Adverse Effects to Discuss
- Excessive daytime sedation and drowsiness (most common reason for discontinuation) 2, 6
- Dizziness and orthostatic hypotension, especially when changing positions 2
- Psychomotor impairment—caution against driving or operating machinery until effects are known 2
- Potential for tolerance to develop with chronic use 6
Serious but Rare Risks
- Priapism (erection lasting >6 hours)—requires immediate medical attention 2
- QT prolongation and cardiac arrhythmias 2
- Visual problems including eye pain, vision changes, or eye swelling 2
Alternative Approaches to Consider
Preferred FDA-Approved Options
- Zolpidem 10 mg for sleep onset 1, 3
- Eszopiclone 2-3 mg for sleep onset and maintenance 1, 3
- Low-dose doxepin 3-6 mg for sleep maintenance 1, 3
- Suvorexant for sleep maintenance 3
Non-Pharmacologic First-Line Treatment
- Cognitive behavioral therapy for insomnia (CBT-I) should be offered as initial treatment before any pharmacotherapy 3
Clinical Bottom Line
While this combination is used frequently in clinical practice and can be done safely with appropriate monitoring, the patient should be counseled that trazodone is not a guideline-recommended first-line treatment for insomnia 3. If choosing to proceed, use the lowest effective dose (starting at 25 mg), monitor closely for serotonin syndrome symptoms during the first few weeks, and reassess the ongoing need for trazodone regularly 1, 3. Consider referral for CBT-I or trial of FDA-approved hypnotics if trazodone proves ineffective or poorly tolerated 3.