Summary

The interaction between lithium and NSAIDs is clinically significant and potentially dangerous. NSAIDs can increase lithium blood levels by reducing kidney clearance, leading to lithium toxicity with symptoms including tremor, confusion, and kidney dysfunction.

Introduction

Lithium is a mood stabilizer primarily used to treat bipolar disorder and prevent manic episodes. It belongs to the class of antimanic agents and requires careful monitoring due to its narrow therapeutic window. NSAIDs (nonsteroidal anti-inflammatory drugs) are a widely used class of medications that include both prescription drugs like diclofenac and naproxen, as well as over-the-counter options such as ibuprofen and aspirin. They work by inhibiting cyclooxygenase enzymes to reduce inflammation, pain, and fever.

Mechanism of Interaction

NSAIDs interact with lithium through a renal mechanism. NSAIDs inhibit cyclooxygenase enzymes, which reduces prostaglandin E2 (PGE2) production in the kidneys. PGE2 normally promotes sodium and lithium excretion through the renal tubules. When PGE2 levels decrease due to NSAID use, the kidneys retain more sodium and lithium, leading to increased lithium reabsorption and elevated serum lithium concentrations. This mechanism can result in lithium levels rising by 15-60% within days of starting NSAID therapy.

Risks and Symptoms

The primary risk of this interaction is lithium toxicity, which can be life-threatening. Early signs include nausea, vomiting, diarrhea, drowsiness, muscle weakness, and tremor. Severe toxicity can progress to confusion, seizures, coma, cardiac arrhythmias, and acute kidney injury. The risk is highest with long-term NSAID use, higher NSAID doses, and in patients with pre-existing kidney disease, dehydration, or those taking other medications that affect kidney function. Even short-term NSAID use can precipitate toxicity in susceptible patients, making this interaction particularly concerning given the widespread availability of over-the-counter NSAIDs.

Management and Precautions

Patients on lithium should generally avoid NSAIDs when possible. If NSAID use is necessary, close monitoring is essential, including checking lithium levels within 4-7 days of starting the NSAID and weekly thereafter. Baseline kidney function should be assessed, and patients should be educated about early toxicity symptoms. Consider alternative pain management options such as acetaminophen, topical analgesics, or non-pharmacological approaches. If NSAIDs must be used, choose the lowest effective dose for the shortest duration possible. Ensure adequate hydration and avoid other nephrotoxic medications. Healthcare providers should maintain a high index of suspicion for lithium toxicity and be prepared to discontinue the NSAID and potentially reduce lithium dosing if levels become elevated.

Lithium interactions with food and lifestyle

Lithium has several important food and lifestyle interactions that require careful monitoring. Sodium intake significantly affects lithium levels - both low sodium diets and sudden increases in sodium intake can alter lithium concentrations and potentially lead to toxicity or reduced effectiveness. Patients should maintain consistent sodium intake and avoid drastic dietary changes. Adequate fluid intake (8-10 glasses of water daily) is essential, as dehydration can increase lithium levels and risk of toxicity. Caffeine intake should be kept consistent, as sudden changes in caffeine consumption can affect lithium levels. Alcohol should be avoided or used with extreme caution, as it can increase the risk of lithium toxicity and may worsen mood symptoms. Patients should also avoid excessive sweating through intense exercise or saunas without proper hydration, as fluid loss can concentrate lithium levels. These interactions are well-documented in major drug databases and clinical guidelines, requiring regular monitoring of lithium blood levels.

NSAID interactions with food and lifestyle

NSAIDs should be avoided with alcohol consumption as this combination significantly increases the risk of gastrointestinal bleeding and stomach ulcers. Taking NSAIDs with food or milk can help reduce stomach irritation and gastrointestinal side effects. Patients should avoid taking NSAIDs on an empty stomach when possible. Additionally, NSAIDs may interact with certain herbal supplements like ginkgo biloba, garlic, and ginger, which can increase bleeding risk when used together.