Can Sertraline and Escitalopram Be Taken Together?
No, sertraline and escitalopram should not be taken together due to the significant risk of serotonin syndrome, a potentially life-threatening condition that can develop when combining two SSRIs. 1, 2
Why This Combination Is Dangerous
Combining two SSRIs like sertraline and escitalopram creates an additive serotonergic effect that substantially increases the risk of serotonin syndrome. The American Academy of Child and Adolescent Psychiatry specifically identifies combining SSRIs (including fluoxetine, paroxetine, citalopram, escitalopram, and sertraline) as a high-risk scenario requiring caution. 2
Clinical Presentation of Serotonin Syndrome
Serotonin syndrome typically manifests within 24-48 hours after combining serotonergic medications and presents with a characteristic triad: 2
- Mental status changes (confusion, agitation, hallucinations)
- Neuromuscular hyperactivity (tremor, rigidity, myoclonus, hyperreflexia)
- Autonomic instability (fever, tachycardia, hypertension, diaphoresis)
In severe cases, this can progress to seizures, arrhythmias, hyperthermia, unconsciousness, and potentially fatal outcomes. 2
Why Patients Might Consider This Combination (And Why It's Wrong)
There is no therapeutic rationale for combining two SSRIs. Both medications work through the same mechanism—selective serotonin reuptake inhibition—so combining them provides no additional benefit beyond what a single SSRI at an appropriate dose would achieve. 3 If one SSRI is inadequate, the evidence-based approach is to:
- Optimize the dose of the current SSRI within its therapeutic range 1
- Switch to a different SSRI (not add a second one) 3
- Consider augmentation with a different class of medication (such as an SNRI or combining with CBT) 1
What To Do If Already Taking Both
Immediate discontinuation of both serotonergic agents is required if serotonin syndrome is suspected, along with hospital-based supportive care including continuous cardiac monitoring and IV fluids. 2 In severe cases, intensive care with serotonin antagonists such as cyproheptadine may be necessary. 2
If a patient is currently taking both medications without symptoms, consult with the prescribing physician immediately to develop a safe tapering plan, as abrupt discontinuation of SSRIs can cause discontinuation syndrome (particularly with sertraline). 1
Critical Pitfalls to Avoid
- Never assume that because both are SSRIs, they can be safely combined—this is precisely why they cannot be combined 2
- Do not overlook over-the-counter medications (dextromethorphan, St. John's Wort) or other prescription medications (tramadol, triptans) that could further increase serotonin syndrome risk 2
- Recognize that drug interactions matter: sertraline interacts with drugs metabolized by CYP2D6, which can complicate the clinical picture 1