Nassir Ghaemi, MD, MPH


June 16, 2017

Lithium's Safety Profile

Dana Wang, MD, a senior resident in the Harvard South Shore program, reviewed the kidney effects of lithium and the latest studies quantifying those harms. For instance, in recent data from Sweden, lithium was associated with end-stage renal failure in about 1% of all patients who were treated with it—an effect that occurred over a mean of more than 20 years of treatment.

The rate is somewhat higher if the sample is limited to those who take lithium for a minimum of 10 years; in that case, up to 5% of patients may develop end-stage renal disease eventually. Although these numbers are important, they also indicate that over 95% of lithium-treated persons never develop end-stage renal disease.

Multiple daily dosing of lithium is a major risk factor for such chronic renal harm, and it is a preventable one, because lithium has a half-life of 24 hours and only needs to be dosed once daily. Furthermore, keeping lithium levels low, and thus avoiding acute lithium toxicity, is another preventable risk factor for chronic renal impairment. By dosing lithium once daily at night and at the lowest dose feasible, the risk for long-term kidney harm with lithium can be reduced even further.

Dr Osser ended the symposium by discussing how to manage other lithium-related side effects. He noted that lithium causes less weight gain than divalproex or commonly used antipsychotics, such as olanzapine and quetiapine. Thus, if those agents are used, so should lithium. He also noted some ways in which weight gain can be ameliorated with lithium: for example, educating patients to avoid consuming caloric beverages (such as sodas) when managing lithium-related thirst. Water retention with lithium can be managed by using amiloride. Carbohydrate craving is an important aspect of lithium-related weight gain, and the most difficult to manage.


I provided a commentary at the end of the symposium, where I noted that our oldest drugs are our most effective: electroconvulsive therapy, lithium, monoamine oxidase inhibitors, and clozapine. All of the new drugs developed since the 1970s have not advanced greater efficacy for any major psychiatric condition. They do have fewer side effects, which is important. But the case of lithium reminds us that we should not assume that newer is better.

All patients should be told about the potential range of benefits of lithium, in terms of mortality/suicide and neuroprotection/dementia prevention, in addition to its well-proven mood benefits. If this is understood, then many patients and doctors would perhaps also understand how these benefits could outweigh the risks of lithium. Such risks should be considered limited, with about 1% long-term kidney risk and less weight gain than other commonly used agents.

To paraphrase Frederick Goodwin, in bipolar illness, you don't need a reason to give lithium. You need reasons not to give it.


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