How should clinicians choose one lithium formulation over another?

Join Craig Chepke, MD, DFAPA, medical director of Excel Psychiatric Associates, as he demystifies the complexities of lithium formulations in bipolar disorder treatment. In this Q&A, Dr Chepke discusses why the conventional wisdom surrounding lithium dosing may be outdated and why once-daily dosing at night is often the best choice for most patients. He also explains the specific scenarios where extended-release lithium might be preferable, especially for patients experiencing gastrointestinal side effects. 

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Answers have been lightly edited for clarity. 

Evi Arthur, Psych Congress Network: Can you talk about different formulations of lithium, why you might choose one over another?

Dr Chepke: We have several formulations of lithium and it may be confusing, especially to people who didn't get good training in this. We've got the traditional lithium, which the label indication says to give it 3 times a day. We have the lithium extender-release, which on the label says to give it twice a day. Well, newsflash, both of those should be given once daily, at night, for most patients. It might be strange to hear that because it's contrary to what the label says, but the label is not always reflective of the most up-to-date science. The label often gets frozen in time and then even new research coming out doesn't necessarily change what the prescribing information says. Lithium has a phenomenally long half-life, somewhere between 24 to 48 hours, so at steady state, it makes no difference if you give it once a day, twice a day, 3 times a day, etc. There have been clinical studies that note once-daily dosing does not negatively impact efficacy.

The reasons why we would consider giving it once a day are several-fold. One is adherence, it's a lot easier to remember to take something once a day than twice or 3 times a day. Though, paradoxically, it actually has less negative impact on the kidneys if you give a large dose all at night, than if you split it up multiple times throughout the day. The overall length of time that the kidneys are exposed to lithium, at higher concentrations, is what determines the actual nephrotoxicity. So if giving it 3 times a day, the kidneys are being exposed at higher concentrations throughout the day. It's the same thing with the extended-release; you're exposing the kidneys longer. Whereas with the once-daily dosing, even though the Cmax is higher, that is less detrimental to the kidneys.

When would you want to use one versus the other? Well, the main benefit of the extended-release lithium is if it has a half-life north of 24 hours, you don't need to have an extended-release to give all-day coverage. Most extended-release medications blunt the Cmax so you don't get as high of a peak lithium level and that can be a key contributor to gastrointestinal side effects.

If you have someone who is taking the traditional instant-release lithium, all at night, and they're getting some GI side effects from it, then that would be a reason to use the extended-release lithium. I'd switch over to the same dose, but extended-release because it's going to blunt that maximum concentration, which can be a little bit easier on the stomach. It's a trade-off because over time, it does expose the kidneys to higher levels of lithium for longer, but if they can't take it because of the GI side effects, then you lose the benefit altogether.

Just to sum things up, if you can, always dose lithium once-daily, at night, for all patients, and I would only use the extended-release if someone has GI side effects with the instant-release lithium.

Dr Craig Chepke is a board-certified psychiatrist in clinical practice as the medical director of Excel Psychiatric Associates in Huntersville, NC, and is an adjunct associate professor of psychiatry for the Sandra and Leon Levine Psychiatry Residency Program at Atrium Health. He attended NYU School of Medicine and completed his psychiatry training at Duke University. As part of an interdisciplinary treatment team in his practice, he employs a person-centered care model to tailor treatments to each individual's needs, integrating traditional pharmacotherapy with psychotherapeutic and physical health and wellness interventions. His clinical and academic interests include serious mental illness, movement disorders, ADHD, and sleep medicine. Dr Chepke is the scientific director for the Psych Congress portfolio of CME conferences, and he has been recognized as a Distinguished Fellow of the American Psychiatric Association.