Summary

The interaction between lithium and NSAIDs is clinically significant and potentially dangerous. NSAIDs can increase lithium blood levels by reducing its renal clearance, leading to lithium toxicity even at previously therapeutic doses.

Introduction

Lithium is a mood stabilizer primarily used to treat bipolar disorder and as an adjunct therapy for major depressive disorder. It belongs to the class of antimanic agents and has a narrow therapeutic window. NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) are a widely used class of medications that include both prescription drugs like diclofenac, naproxen, and celecoxib, as well as over-the-counter medications such as ibuprofen and aspirin. They are commonly used for pain relief, inflammation reduction, and fever management.

Mechanism of Interaction

NSAIDs interact with lithium through a renal mechanism involving prostaglandin inhibition. NSAIDs block cyclooxygenase enzymes, reducing prostaglandin E2 (PGE2) synthesis in the kidneys. PGE2 normally promotes lithium excretion by inhibiting sodium reabsorption in the distal nephron. When NSAIDs reduce PGE2 levels, sodium reabsorption increases, and since lithium follows sodium transport, lithium reabsorption also increases. This leads to decreased lithium clearance and elevated serum lithium concentrations, potentially reaching toxic levels.

Risks and Symptoms

The primary risk of this interaction is lithium toxicity, which can be life-threatening. Symptoms include nausea, vomiting, diarrhea, tremor, confusion, ataxia, and in severe cases, seizures, coma, and death. Even short-term NSAID use can significantly increase lithium levels within days. The risk is particularly high in elderly patients, those with kidney disease, or dehydration. Additionally, both drug classes can independently cause kidney dysfunction, and their combination may increase the risk of acute kidney injury. The interaction can occur with all NSAIDs, including selective COX-2 inhibitors, though the magnitude may vary between different agents.

Management and Precautions

Close monitoring is essential when NSAIDs must be used with lithium. Obtain baseline lithium levels before starting NSAIDs and monitor levels within 4-7 days of initiation, then weekly until stable. Consider reducing lithium dose by 25-50% when starting NSAIDs, with dose adjustments based on serum levels. Educate patients about lithium toxicity symptoms and advise them to avoid over-the-counter NSAIDs. When possible, use alternative pain management strategies such as acetaminophen, topical analgesics, or non-pharmacological approaches. If NSAIDs are discontinued, monitor for subtherapeutic lithium levels and adjust doses accordingly. Maintain adequate hydration and monitor kidney function regularly.

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.

NSAIDs interactions with food and lifestyle

NSAIDs should be taken with food or milk to reduce gastrointestinal irritation and risk of stomach ulcers. Alcohol consumption should be avoided or limited while taking NSAIDs as it significantly increases the risk of gastrointestinal bleeding and stomach ulcers. Patients should also avoid smoking, as it can increase the risk of gastrointestinal complications when combined with NSAID use.