Summary

Citalopram and escitalopram are both SSRI antidepressants that should not be used together due to increased risk of serotonin syndrome and enhanced side effects. Since escitalopram is the active S-enantiomer of citalopram, concurrent use provides no therapeutic benefit while significantly increasing toxicity risk.

Introduction

Citalopram (Celexa) is a selective serotonin reuptake inhibitor (SSRI) antidepressant used to treat major depressive disorder and anxiety disorders. It works by blocking the reuptake of serotonin in the brain, increasing serotonin availability. Escitalopram (Lexapro) is also an SSRI antidepressant that treats depression and generalized anxiety disorder. Notably, escitalopram is the S-enantiomer of citalopram, meaning it contains only the therapeutically active portion of the citalopram molecule, making it more potent and selective.

Mechanism of Interaction

The interaction between citalopram and escitalopram occurs through additive pharmacological effects on serotonin reuptake inhibition. Both medications block the serotonin transporter (SERT), preventing serotonin reuptake and increasing synaptic serotonin concentrations. When used together, this creates excessive serotonergic activity that can lead to serotonin syndrome. Additionally, since escitalopram is derived from citalopram, concurrent use essentially results in taking two forms of the same medication, leading to enhanced side effects without additional therapeutic benefit.

Risks and Symptoms

The primary risk of combining citalopram and escitalopram is serotonin syndrome, a potentially life-threatening condition characterized by altered mental status, autonomic instability, and neuromuscular abnormalities. Symptoms may include agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and hyperthermia. Additional risks include increased incidence of common SSRI side effects such as nausea, diarrhea, headache, dizziness, sexual dysfunction, and sleep disturbances. There is also an elevated risk of QT prolongation and cardiac arrhythmias, particularly with citalopram at higher doses.

Management and Precautions

Citalopram and escitalopram should never be prescribed together. If switching between these medications, a washout period is typically not required since they have similar mechanisms, but the transition should be done gradually under medical supervision. When switching from citalopram to escitalopram, the dose should be adjusted appropriately since escitalopram is more potent (typically half the citalopram dose). Patients should be monitored for signs of serotonin syndrome, especially during the first few weeks of treatment or dose changes. Healthcare providers should review all medications, including over-the-counter drugs and supplements, to identify other serotonergic agents that could contribute to the interaction risk.

Citalopram interactions with food and lifestyle

Alcohol: Citalopram may increase the sedative effects of alcohol. Patients should avoid or limit alcohol consumption while taking citalopram as it can worsen depression symptoms and increase the risk of drowsiness, dizziness, and impaired judgment. Grapefruit: While not a major interaction, grapefruit juice may slightly increase citalopram levels in the blood. Patients should consult their healthcare provider about grapefruit consumption. MAO inhibitors and certain foods: Patients taking citalopram should avoid tyramine-rich foods (aged cheeses, cured meats, fermented foods) if they have recently discontinued or are transitioning from MAO inhibitors, though this is more relevant during the washout period between medications.

Escitalopram interactions with food and lifestyle

Alcohol: Escitalopram may increase the effects of alcohol and impair mental and motor skills. Patients should avoid or limit alcohol consumption while taking escitalopram as recommended by clinical guidelines and major drug databases. The combination can increase sedation, dizziness, and may worsen depression symptoms.