Safe Use of Sertraline, Bupropion, and Trazodone Combination

Introduction to Combination Therapy

• The American Academy of Family Physicians suggests that sertraline is well-tolerated compared to other SSRIs and has less effect on metabolism of other medications 1
• The American Academy of Family Physicians recommends that bupropion should have its second dose given before 3 PM to minimize insomnia risk 1, 2

Safety and Efficacy

• The American Academy of Sleep Medicine suggests that trazodone at 25 mg is a low dose typically used for sleep, though guidelines suggest clinicians NOT use trazodone as a treatment for insomnia based on 50 mg dose trials 3, 4
• The American Academy of Sleep Medicine recommends considering FDA-approved sleep medications instead of trazodone for insomnia treatment 3, 4

Dosing and Administration

• The American Academy of Family Physicians suggests that bupropion doses should be given with the second dose before 3 PM to prevent insomnia 1, 2
• The National Comprehensive Cancer Network recommends administering trazodone 25 mg at bedtime for sleep 5
• The American Academy of Family Physicians suggests that sertraline can be given morning or evening 1

Alternative Therapies

• The American Academy of Sleep Medicine recommends zolpidem 10 mg for sleep onset 4
• The American Academy of Sleep Medicine recommends eszopiclone 2-3 mg for sleep onset and maintenance 4
• The American Academy of Sleep Medicine recommends low-dose doxepin 3-6 mg for sleep maintenance 4

Monitoring and Emergency Response

• The American Academy of Sleep Medicine suggests that medications should be introduced gradually, not rapidly titrated, to minimize the risk of serotonin syndrome 6
• The National Comprehensive Cancer Network recommends providing supportive care, including cooling measures if hyperthermic, in cases of serotonin syndrome 5
• The American Academy of Family Physicians recommends seeking emergency medical attention for severe cases of serotonin syndrome 1