Is it safe to take trazodone and Lexapro (escitalopram) together?

Safety of Taking Trazodone and Lexapro (Escitalopram) Together

Trazodone and Lexapro (escitalopram) can be safely taken together with appropriate monitoring, but caution is needed due to the potential risk of serotonin syndrome when combining multiple serotonergic medications. 1

Pharmacological Considerations

Mechanism of Action

• Escitalopram (Lexapro): Selective serotonin reuptake inhibitor (SSRI)
• Trazodone: Non-selective serotonin reuptake inhibitor with anxiolytic and sedative/hypnotic effects

Potential Interactions

1. Serotonin Syndrome Risk

   • Both medications affect serotonergic neurotransmission
   • Combining two serotonergic drugs requires caution and monitoring 1
   • Symptoms of serotonin syndrome can develop within 24-48 hours and include:
     • Mental status changes (confusion, agitation, anxiety)
     • Neuromuscular hyperactivity (tremors, clonus, hyperreflexia)
     • Autonomic hyperactivity (hypertension, tachycardia, diaphoresis)

2. Pharmacokinetic Interactions

   • Research shows no significant pharmacokinetic interaction between trazodone and SSRIs like citalopram and fluoxetine 2
   • This suggests no significant metabolic interaction that would alter drug levels

Clinical Evidence

• A 2004 study found no significant metabolic interaction between trazodone and citalopram/fluoxetine, with no adverse effects including serotonin syndrome observed 2

• However, case reports have documented adverse events:

  • A case of jitteriness/anxiety syndrome was reported when celecoxib was added to a patient already on escitalopram and trazodone 3
  • A case of manic episode was reported after adding trazodone to escitalopram treatment 4

Monitoring and Precautions

When using this combination:

1. Start with Low Doses

   • Begin with lower doses of both medications and increase gradually
   • Monitor for symptoms especially in the first 24-48 hours after dosage changes 1

2. Watch for Serotonin Syndrome

   • Monitor for early signs: confusion, agitation, tremors, sweating, diarrhea
   • Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness 1
   • If symptoms appear, discontinue medications and seek immediate medical attention

3. Special Populations

   • Elderly patients may require lower doses due to reduced clearance
   • Patients with hepatic or renal impairment may need dose adjustments

Common Clinical Applications

This combination is often used when:

• Escitalopram alone doesn't adequately control depression/anxiety
• Sleep disturbances persist despite escitalopram therapy (trazodone is added for its sedative effects)

Conclusion

While trazodone and escitalopram can be safely used together with appropriate monitoring, the combination should be approached with caution due to the theoretical risk of serotonin syndrome. The benefits of improved depression control and sleep must be weighed against potential risks.