Summary

Desipramine and fluvoxamine have a clinically significant drug interaction where fluvoxamine can substantially increase desipramine blood levels. This interaction occurs through fluvoxamine's inhibition of CYP2D6, the primary enzyme responsible for desipramine metabolism, potentially leading to tricyclic antidepressant toxicity.

Introduction

Desipramine is a tricyclic antidepressant (TCA) primarily used to treat major depressive disorder and sometimes prescribed off-label for neuropathic pain and attention deficit hyperactivity disorder. It works by blocking the reuptake of norepinephrine and, to a lesser extent, serotonin. Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) antidepressant commonly prescribed for major depressive disorder, obsessive-compulsive disorder, and various anxiety disorders. Both medications affect neurotransmitter levels in the brain but through different mechanisms and metabolic pathways.

Mechanism of Interaction

The interaction between desipramine and fluvoxamine occurs through cytochrome P450 enzyme inhibition. Fluvoxamine is a potent inhibitor of CYP2D6, the primary enzyme responsible for metabolizing desipramine. When fluvoxamine inhibits CYP2D6, it significantly reduces the clearance of desipramine from the body, leading to elevated plasma concentrations. This can result in a 2-5 fold increase in desipramine levels, depending on the individual's metabolic profile and dosing regimens. The inhibition is competitive and reversible, but the effects can persist for several days after fluvoxamine discontinuation due to the drug's half-life.

Risks and Symptoms

The primary risk of this drug interaction is tricyclic antidepressant toxicity due to elevated desipramine levels. Symptoms may include cardiac arrhythmias, prolonged QT interval, hypotension, anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision), central nervous system effects (confusion, agitation, seizures), and potentially life-threatening cardiotoxicity. Patients may also experience increased sedation, dizziness, and orthostatic hypotension. The interaction is considered major and clinically significant, requiring careful monitoring or alternative treatment strategies. Elderly patients and those with pre-existing cardiac conditions are at particularly high risk for serious adverse effects.

Management and Precautions

Desipramine interactions with food and lifestyle

Alcohol: Avoid alcohol consumption while taking desipramine as it may increase sedation, drowsiness, and impair cognitive function. Alcohol can also worsen depression and interfere with the medication's effectiveness. Smoking: Tobacco smoking may decrease desipramine blood levels by increasing the drug's metabolism, potentially reducing its therapeutic effectiveness. Patients who smoke may require dosage adjustments and should discuss smoking cessation with their healthcare provider.

Fluvoxamine interactions with food and lifestyle

Fluvoxamine should not be taken with alcohol as it may increase drowsiness and impair cognitive function. Caffeine intake should be limited or avoided as fluvoxamine significantly inhibits caffeine metabolism, potentially leading to caffeine toxicity with symptoms including jitteriness, rapid heartbeat, and insomnia. Smoking cessation may be necessary as tobacco use can reduce fluvoxamine effectiveness by increasing its metabolism. Patients should maintain consistent timing of doses with regard to meals, as food can affect absorption, though fluvoxamine can be taken with or without food.