Summary

Citalopram and fluoxetine are both selective serotonin reuptake inhibitors (SSRIs) that can interact when used together, potentially leading to increased serotonin levels and risk of serotonin syndrome. This interaction is considered clinically significant and requires careful monitoring and management.

Introduction

Citalopram (Celexa) is a selective serotonin reuptake inhibitor (SSRI) antidepressant commonly prescribed for major depressive disorder and anxiety disorders. Fluoxetine (Prozac) is also an SSRI antidepressant used to treat depression, obsessive-compulsive disorder, panic disorder, and bulimia nervosa. Both medications work by blocking the reuptake of serotonin in the brain, increasing serotonin availability at synaptic sites. When these two SSRIs are used concurrently or in close succession, their combined effects on serotonin levels can lead to potentially serious interactions.

Mechanism of Interaction

The interaction between citalopram and fluoxetine occurs through their shared mechanism of serotonin reuptake inhibition. Both drugs block the serotonin transporter (SERT), preventing the reuptake of serotonin from the synaptic cleft. When used together, this dual inhibition can lead to excessive accumulation of serotonin, particularly in the central nervous system. Additionally, fluoxetine and its active metabolite norfluoxetine have long half-lives (1-3 days and 4-16 days respectively), which can prolong the interaction even after discontinuation. The combined serotonergic activity increases the risk of serotonin syndrome, a potentially life-threatening condition characterized by altered mental status, autonomic instability, and neuromuscular abnormalities.

Risks and Symptoms

The primary risk of combining citalopram and fluoxetine is serotonin syndrome, which can range from mild to severe and potentially fatal. Symptoms include confusion, agitation, hyperthermia, diaphoresis, tremor, muscle rigidity, hyperreflexia, and in severe cases, seizures, coma, and cardiovascular collapse. Additional risks include increased side effects common to both medications such as nausea, headache, dizziness, and sexual dysfunction. The interaction may also lead to prolonged QT interval, particularly with citalopram, increasing the risk of cardiac arrhythmias. Patients may experience enhanced CNS effects including sedation, cognitive impairment, and increased fall risk, especially in elderly populations.

Management and Precautions

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.

Fluoxetine interactions with food and lifestyle

Alcohol: Fluoxetine may increase the sedative effects of alcohol and impair cognitive and motor performance. Patients should avoid or limit alcohol consumption while taking fluoxetine. Grapefruit juice: May increase fluoxetine blood levels, though this interaction is generally considered minor. St. John's Wort: Should be avoided as it may increase the risk of serotonin syndrome when combined with fluoxetine.