From the Research
Trazodone and nefazodone should not be used together due to a significant risk of serious drug interactions, particularly the risk of serotonin syndrome, as reported in a case study where a patient developed delayed-onset serotonin syndrome after ingesting a mixture of serotonergic agents, including trazodone 1. The use of both medications, which are serotonergic antidepressants, can cause serotonin syndrome, a potentially life-threatening condition characterized by agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and hyperthermia. Additionally, both medications may interact with each other through pharmacokinetic mechanisms, such as the inhibition of CYP3A4 enzymes in the liver, which can lead to increased blood levels of either drug, enhancing side effects like sedation, dizziness, and hypotension. Some studies have reported on the risk of adverse drug events due to drug-drug interactions, highlighting the importance of careful consideration when prescribing multiple medications, especially in older patients with multiple health conditions 2. A meta-analysis comparing trazodone and nefazodone with selective serotonin reuptake inhibitors for the treatment of major depressive disorder found that the two classes of medications had similar efficacy and tolerability, but this does not address the safety of using them together 3. If treatment with either medication is necessary, only one should be used, and a washout period of at least 1-2 weeks is recommended when switching between them, as suggested by general principles of drug interaction management 4. Alternative antidepressant combinations with lower interaction potential should be considered if multiple medications are needed. Any patient experiencing symptoms of serotonin syndrome while taking these medications should seek immediate medical attention. Always consult with a healthcare provider before making any changes to medication regimens.