Summary

Citalopram and linezolid have a significant drug interaction that can lead to serotonin syndrome, a potentially life-threatening condition. This interaction occurs because linezolid has monoamine oxidase inhibitor (MAOI) properties that can dangerously increase serotonin levels when combined with the SSRI citalopram.

Introduction

Citalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant commonly prescribed for depression and anxiety disorders. It works by increasing serotonin levels in the brain by blocking its reuptake. Linezolid is an oxazolidinone antibiotic used to treat serious gram-positive bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). While primarily an antibiotic, linezolid also possesses weak monoamine oxidase inhibitor (MAOI) activity, which can lead to significant drug interactions with serotonergic medications.

Mechanism of Interaction

The interaction between citalopram and linezolid occurs through complementary mechanisms that both increase serotonin availability. Citalopram blocks the serotonin transporter (SERT), preventing the reuptake of serotonin from synaptic clefts and increasing extracellular serotonin concentrations. Linezolid, while primarily targeting bacterial protein synthesis, also inhibits monoamine oxidase A and B enzymes, which are responsible for metabolizing serotonin, norepinephrine, and dopamine. When used together, citalopram increases serotonin release while linezolid decreases serotonin metabolism, creating a synergistic effect that can lead to excessive serotonin accumulation and potentially trigger serotonin syndrome.

Risks and Symptoms

The primary risk of combining citalopram and linezolid is serotonin syndrome, a potentially fatal condition characterized by altered mental status, autonomic instability, and neuromuscular abnormalities. Symptoms may include confusion, agitation, hyperthermia, diaphoresis, tremor, muscle rigidity, hyperreflexia, and in severe cases, seizures, coma, and cardiovascular collapse. The risk is particularly elevated in patients taking higher doses of citalopram, those with compromised kidney or liver function, elderly patients, and individuals taking multiple serotonergic medications. The interaction is considered major and clinically significant, with onset typically occurring within hours to days of concurrent administration.

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.

Linezolid interactions with food and lifestyle

Linezolid has significant interactions with tyramine-rich foods that require careful dietary restrictions. Patients taking linezolid should avoid or limit foods high in tyramine including aged cheeses, cured meats, fermented foods, red wine, beer, and certain vegetables like sauerkraut. Consuming large amounts of tyramine while on linezolid can lead to dangerous increases in blood pressure (hypertensive crisis). Additionally, linezolid can interact with foods and beverages containing high amounts of caffeine, potentially causing increased blood pressure and heart rate. Patients should limit caffeine intake from coffee, tea, energy drinks, and chocolate while taking this medication. Alcohol should be avoided or used with extreme caution as it may increase the risk of side effects and can interact with linezolid's mechanism of action.