Is it safe for a patient to take Lexapro (escitalopram) 15mg, trazodone 150mg every night (qhs), and Sinequan (doxepin) 10mg every night (qhs) together?

Concurrent Use of Lexapro, Trazodone, and Sinequan: Safety Concerns

The combination of Lexapro (escitalopram) 15mg, trazodone 150mg qhs, and Sinequan (doxepin) 10mg qhs poses a significant risk for serotonin syndrome and excessive sedation, and should be modified to a safer regimen. 1, 2

Serotonin Syndrome Risk

The concurrent use of multiple serotonergic agents significantly increases the risk of serotonin syndrome, a potentially life-threatening condition:

• Escitalopram (Lexapro) is an SSRI that increases serotonin levels
• Trazodone, though primarily used for sleep at 150mg, also has serotonergic properties
• Doxepin (Sinequan), a tricyclic antidepressant, also affects serotonin levels

The American Academy of Child and Adolescent Psychiatry guidelines specifically caution against combining multiple serotonergic medications due to this risk 1. Case reports have documented serotonin syndrome occurring with combinations of serotonergic agents, including escitalopram 3, 4.

Excessive Sedation Concerns

This combination presents substantial risk for excessive sedation:

• Both trazodone and doxepin are sedating medications commonly used for insomnia
• The additive sedative effects could lead to:
  • Morning drowsiness
  • Increased fall risk
  • Cognitive impairment
  • Potential respiratory depression

Recommended Approach

1. Eliminate medication redundancy:

   • Maintain Lexapro 15mg for antidepressant effect
   • Choose ONLY ONE sedating agent for sleep:
     • Either trazodone 25-100mg (preferred starting dose per American Psychiatric Association) 2
     • OR doxepin 10mg, but not both

2. If insomnia persists with a single agent:

   • Consider non-pharmacological sleep interventions
   • Evaluate for underlying causes of insomnia
   • Consider alternative medications with less serotonergic activity

Monitoring If Combination Is Continued

If clinical judgment determines the need to maintain this combination temporarily:

• Monitor closely for signs of serotonin syndrome: agitation, tremor, hyperreflexia, hyperthermia, diaphoresis, and autonomic instability 1
• Start with lower doses of each medication and titrate slowly
• Educate the patient about warning signs requiring immediate medical attention
• Schedule frequent follow-up appointments to assess response and side effects

Important Precautions

• Avoid adding any additional serotonergic medications to this regimen
• Be particularly cautious in elderly patients or those with hepatic impairment
• Consider potential drug interactions through CYP450 pathways
• Case reports have documented manic episodes when trazodone was added to escitalopram treatment 3

This medication combination presents unnecessary risks when safer alternatives exist. The therapeutic benefit of using two sedating agents (trazodone and doxepin) simultaneously is questionable and increases the potential for adverse effects.