Medications That Interact with Lithium
Lithium has numerous significant drug interactions that can lead to toxicity due to its narrow therapeutic window. NSAIDs, diuretics, ACE inhibitors, and several other medications should be avoided or used with extreme caution in patients taking lithium. 1, 2
Major Drug Interactions with Lithium
Medications That Increase Lithium Levels
NSAIDs (Non-steroidal anti-inflammatory drugs): These medications decrease lithium clearance and increase serum lithium levels, potentially leading to toxicity 1
- Indomethacin and piroxicam have been reported to significantly increase steady-state plasma lithium concentrations 1
- COX-2 inhibitors like celecoxib can increase lithium levels by approximately 17% 1
- Naproxen can increase serum lithium levels by up to 41.9% in some individuals 3
- Sulindac appears to be a safer NSAID option as it has not been shown to significantly affect lithium levels 4
Diuretics: Can significantly reduce lithium clearance 2
ACE Inhibitors and ARBs: Reduce renal clearance of lithium 1
Antibiotics: Associated with elevated lithium levels in clinical practice 6
- Contribute significantly to drug-interaction-related lithium toxicity 6
Other Significant Interactions
Haloperidol: Combined use with lithium has been associated with an encephalopathic syndrome followed by irreversible brain damage in some cases 1
- Similar adverse interactions may occur with other antipsychotic medications 1
Neuromuscular blocking agents: Lithium may prolong their effects 1
Electroconvulsive therapy (ECT): Reports of acute brain syndrome when lithium is used concurrently with ECT 7
- It is recommended to avoid lithium during ECT treatment when clinically possible 7
Monoamine oxidase inhibitors (MAOIs): Should be avoided in combination with lithium due to increased risk of serotonin syndrome 7
Multiple serotonergic drugs: Caution should be exercised when combining lithium with other serotonergic medications due to risk of serotonin syndrome 7
Clinical Management of Lithium Interactions
Regular monitoring: All patients taking potentially nephrotoxic agents such as lithium should have their GFR, electrolytes, and drug levels regularly monitored 7
Temporary discontinuation: Lithium should be temporarily discontinued in people with GFR <60 ml/min/1.73 m² who have serious intercurrent illness that increases risk of acute kidney injury 7
Dosage adjustment: When lithium must be used with interacting medications, the lithium dosage may need to be decreased and more frequent monitoring of lithium plasma levels is recommended 1
Special considerations during illness: Decreased tolerance to lithium can occur with protracted sweating, diarrhea, or infection with elevated temperatures, requiring supplemental fluid and salt administration 1
Warning Signs of Lithium Toxicity
- Patients and caregivers should be educated to discontinue lithium and contact their physician if signs of lithium toxicity occur, including: 1
- Diarrhea
- Vomiting
- Tremor
- Mild ataxia
- Drowsiness
- Muscular weakness
Practical Recommendations
When prescribing lithium with potentially interacting medications, more frequent serum lithium level determinations are required until the magnitude of the drug interaction can be adequately assessed 3
Lower lithium doses (blood levels 0.2-0.6 mEq/L) may be adequate when lithium is used to augment antidepressants 7, 8
Irregularity in lithium dispensing pattern is significantly associated with elevated lithium levels, highlighting the importance of medication adherence 6