Top 5 Lithium Drug Interactions

phenytoin drug interactions

Lithium has numerous clinical pearls that are essential to remember. Of all the educational points about this medication, you must remember some of these important lithium drug interactions. The list below is not an all-inclusive list, just ones that more commonly occur in clinical practice.


NSAIDs are well known to impact the serum concentration of lithium in an upward direction. This could lead our patient into toxicity. What makes NSAIDs even more risky is that they are available over the counter. Diligent patient education should be done for anyone taking lithium and advised to speak with their pharmacist and provider prior to starting any new OTC medications. Here’s a case scenario regarding this interaction.


Caffeine is more likely to the opposite compared to NSAIDs. Caffeine can reduce concentrations of lithium. Checking levels, quick identification of treatment failure, and recognition of altered caffeine habits can be really helpful to prevent negative outcomes and fluctuating levels.

ACE Inhibitors/ARBs

These drugs are incredibly common for management of hypertension. Because they generally don’t have a ton of drug interactions compared to other agents, they may be overlooked by a prescribing provider. ACE inhibitors and ARBs can significantly raise the concentrations of lithium, potentially leading to toxicity.

Serotonergic Drugs

There is a caution with regards to the use of lithium and other drugs that may have serotonin activity. This results in a laundry list of medications that may increase the risk of serotonin syndrome. SSRI’s, SNRI’s, TCA’s, MAOI’s, and tramadol are a few medications that come to mind with serotonergic activity.

Thiazide Diuretics

Even though these drugs are classified as diuretics, it can uniquely reduce the excretion of lithium. Patients who need to be on thiazides and lithium should be monitored closely for increasing levels and signs of lithium toxicity. Ideally, another non-interacting agent could be chosen in place of the thiazide in our patients on lithium.

If you’d like to learn more about lithium drug interactions and other critical information, you can listen to that specific podcast right here!

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Written By Eric Christianson

September 18, 2019

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