Is there a drug interaction between citalopram (Selective Serotonin Reuptake Inhibitor) and sertraline (Selective Serotonin Reuptake Inhibitor)?

Drug Interaction Between Citalopram and Sertraline

Yes, there is a significant drug interaction between citalopram and sertraline that can lead to serotonin syndrome, a potentially life-threatening condition. These medications should not be used concurrently. 1

Mechanism of Interaction

• Both citalopram and sertraline are Selective Serotonin Reuptake Inhibitors (SSRIs) that work by increasing serotonin levels in the brain 1
• Combining two serotonergic medications significantly increases the risk of serotonin syndrome due to excessive serotonin accumulation in the central nervous system 1
• While each SSRI has different pharmacokinetic properties, their pharmacodynamic effects are similar, making concurrent use redundant and dangerous 2, 3

Clinical Manifestations of Serotonin Syndrome

Serotonin syndrome typically develops within 24-48 hours of combining serotonergic medications and presents with:

• Mental status changes: confusion, agitation, anxiety 1
• Neuromuscular hyperactivity: tremors, clonus, hyperreflexia, muscle rigidity 1
• Autonomic hyperactivity: hypertension, tachycardia, arrhythmias, tachypnea, diaphoresis, shivering, vomiting, diarrhea 1
• Advanced symptoms: fever, seizures, arrhythmias, unconsciousness (potentially fatal) 1

Pharmacological Considerations

• Citalopram has less effect on CYP450 isoenzymes compared to other SSRIs, giving it a lower propensity for drug interactions, but this does not mitigate the serotonergic effects when combined with sertraline 1
• Sertraline moderately inhibits CYP2D6, while citalopram has minimal effect on this enzyme 2
• The primary concern is not the metabolic interaction but the additive serotonergic effects 1

Management Recommendations

• Never combine citalopram and sertraline due to the high risk of serotonin syndrome 1
• If switching between these medications:
  • Allow for an appropriate washout period based on the half-life of the medication being discontinued 1
  • Sertraline has a shorter half-life than fluoxetine, requiring approximately 1-2 weeks washout 1
• If serotonin syndrome occurs, treatment includes:
  • Immediate discontinuation of all serotonergic agents 1
  • Hospital-based supportive care with continuous cardiac monitoring 1
  • Benzodiazepines may be used for symptom control 4

Clinical Pitfalls to Avoid

• Do not mistake serotonin syndrome for neuroleptic malignant syndrome, as the treatments differ 4
• Be aware that serotonin syndrome can occur rapidly (within hours) after combining serotonergic medications 4
• Remember that even when switching from one SSRI to another, there is a risk of interaction if adequate washout time is not observed 1
• Patients on either citalopram or sertraline should be cautioned against taking over-the-counter medications containing serotonergic compounds (e.g., St. John's wort, dextromethorphan) 1

In clinical practice, there is never a therapeutic reason to combine these two medications as they belong to the same drug class and work through the same mechanism of action 3.