Safety of Starting Fluvoxamine with Lexapro (Escitalopram)
Starting fluvoxamine while on Lexapro (escitalopram) is NOT safe and should be avoided due to the significant risk of serotonin syndrome from combining two SSRIs. 1, 2
Why This Combination Is Dangerous
Combining two SSRIs like fluvoxamine and escitalopram significantly increases the risk of serotonin syndrome, a potentially life-threatening condition caused by excessive serotonin accumulation in the central nervous system. 1, 2 The FDA labeling for both medications explicitly warns about this risk when combining serotonergic drugs. 1, 2
Serotonin Syndrome: Clinical Manifestations
Serotonin syndrome typically develops within 24-48 hours of combining serotonergic medications and presents with: 3, 1
- Mental status changes: confusion, agitation, anxiety, hallucinations, or loss of consciousness 3, 1
- Neuromuscular hyperactivity: tremors, clonus, hyperreflexia, muscle rigidity, and uncontrolled muscle spasms 3, 1
- Autonomic instability: hypertension, tachycardia, rapid changes in blood pressure, hyperthermia, diaphoresis, tachypnea, and arrhythmias 3, 1
- Advanced symptoms: high fever, seizures, arrhythmias, and unconsciousness—which can be fatal 3, 1
Evidence from Clinical Practice
A case report documented serotonin syndrome in a patient who was switched from paroxetine to fluvoxamine without adequate washout time, resulting in fever, auditory hallucinations, and concentration difficulties that resolved only after discontinuing fluvoxamine. 4 This demonstrates the real-world risk even when transitioning between SSRIs.
Safe Alternatives
If Switching Between SSRIs:
- Allow a washout period based on the half-life of the medication being discontinued before starting the new SSRI 3
- For escitalopram (half-life approximately 27-32 hours), a washout period of at least 1-2 weeks is recommended before starting fluvoxamine 3
If Augmentation Is Needed:
- Do not combine two SSRIs—this is contraindicated 1, 2
- Consider alternative augmentation strategies such as adding a different class of medication (e.g., bupropion, mirtazapine, or atypical antipsychotics at low doses) rather than another SSRI 5
- Both fluvoxamine and escitalopram are approved for social anxiety disorder in Japan and are considered first-line options, but they should be used as monotherapy, not in combination 5
Critical Pitfalls to Avoid
- Never combine two SSRIs concurrently—the risk of serotonin syndrome is unacceptably high 1, 2
- Avoid inadequate washout periods when switching from one SSRI to another, as residual drug levels can still cause dangerous interactions 4
- Warn patients against over-the-counter serotonergic compounds (St. John's wort, dextromethorphan) while on either medication 3
- Do not assume lower doses are safe—serotonin syndrome can occur even with therapeutic doses when SSRIs are combined 1, 4