From the Guidelines
Taking doxepin and trazodone together is generally not recommended without close medical supervision due to the potential for serious drug interactions, including serotonin syndrome, a potentially life-threatening condition 1. Both medications are antidepressants that affect serotonin levels in the brain, and combining them increases the risk of serotonin syndrome, characterized by agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and in severe cases, seizures or loss of consciousness. Some key points to consider when taking these medications together include:
- The risk of serotonin syndrome, which can be triggered when serotonergic medications are combined, with symptoms arising within 24 to 48 hours after combining medications 1.
- The potential for sedation, dizziness, and drowsiness, which can significantly impair the ability to drive or operate machinery.
- The importance of close medical supervision and monitoring for unusual symptoms such as confusion, tremors, excessive sweating, or coordination problems.
- The need to take these medications exactly as prescribed and never adjust the dosage on your own. If your doctor has prescribed both medications, they have likely weighed the benefits against these risks for your specific situation. It is essential to consult with your healthcare provider first to discuss your complete medication regimen and medical history before considering this combination. Additionally, it is crucial to be aware of the potential interactions with other medications, such as opioid drugs, serotonergic/adrenergic drugs, and MAO inhibitors, which can increase the risk of serious adverse reactions 1.
From the Research
Combination of Doxepin and Trazodone
- There is no direct evidence from the provided studies that specifically addresses the combination of doxepin and trazodone 2, 3, 4, 5, 6.
- However, study 4 compares the efficacy and safety of doxepin and trazodone in the therapy of outpatients suffering from depression, suggesting that both drugs have approximately equivalent antidepressive and anxiolytic effects and safety.
- Study 2 assesses the efficacy and acceptability of doxepin, trazodone, and melatonin in improving sleep quality and reducing daytime drowsiness in psychiatric patients, but it does not explore the combination of doxepin and trazodone.
- Study 3 provides an empirically derived guideline for prescribing antidepressant medications, including doxepin and trazodone, but it does not address their combination.
- Studies 5 and 6 discuss the use of antidepressants, including doxepin and trazodone, in the treatment of chronic pain and depression, but they do not provide information on their combined use.
Safety and Efficacy
- The safety and efficacy of doxepin and trazodone as individual treatments are discussed in several studies 2, 3, 4, 5, 6.
- Study 4 suggests that trazodone may have less risk compared to doxepin, while study 2 reports that doxepin has a better tolerability profile than trazodone.
- Study 3 finds that some medications, including doxepin and trazodone, always had remission rates below 11% and therefore were not suitable as single antidepressant therapy for any of the subgroups.
Optimal Administration Time
- Study 6 explores the optimal time of day for taking antidepressants, including doxepin and trazodone, and finds that the optimal time of maximum efficacies for doxepin is at zeitgeber time (ZT) 2, while trazodone has its best therapeutic effects at ZT10.
- However, this study does not address the combination of doxepin and trazodone or their optimal administration time when used together.