Lithium Intoxication Manageable, Say Experts

Although lithium is recommended as a first-line maintenance treatment for bipolar disorder and treatment-refractory depression, some long-term studies have shown that the mood stabilizer can significantly impair renal function.

“Lithium is exclusively excreted by the kidneys, and lithium dosage has to be adapted to renal function,” explained Michael Ott, M.D., a consultant in nephrology and internal medicine at the University Hospital of Umeå University in Sweden. Ott was the lead author of a study published online June 14 in the Journal of Psychopharmacology that recently concluded that lithium intoxication is relatively rare and can be safely managed in most cases.

To determine the frequency of lithium intoxication and assess the connection between toxic lithium levels and acute or chronic renal failure, Ott and colleagues analyzed medical data of 1,340 adult patients who had been exposed to lithium between 1997 and 2013. To estimate the incidence of intoxication, the authors first calculated the episodes per patient treated over the entire 17-year observation period. Next, they estimated the incidence of lithium intoxication per treatment year based on lithium prescribing data from the Swedish National Board of Health and Welfare.

Of the 1,340 patients who had been exposed to lithium over the 17-year period of observation, 96 (7.16 percent) had experienced at least one episode of serum lithium levels equal to or greater than 1.5 mmol/L—the measurement defined by the authors as the cut-off point for a risk of clinically significant intoxication. Patients with severe lithium intoxication most commonly presented with confusion, disorientation, or somnolence. Tremor, vomiting and diarrhea, and ataxia or falls were less likely to occur in an acute overdose setting.

Further analysis of the medical records of 77 patients with lithium intoxication revealed that while acute kidney injury occurred, renal function one month after the episode was similar to renal function at baseline, indicating no trace of chronic kidney disease. No fatalities occurred in connection with lithium intoxication.

“It is reassuring that despite evidence of acute kidney injury, renal functioning had returned to the patients’ pre-acute intoxication levels one month later,” said Vivian Kafantaris, M.D., a lithium expert and the director of research in the Division of Child and Adolescent Psychiatry at Hofstra North Shore-LIJ School of Medicine, who was not involved with this study.

“An important message that psychiatrists can take away from this study is that the signs and symptoms that we generally rely on in clinical practice to assess lithium toxicity, such as vomiting, nausea, tremor, ataxia, or falls, are not reliable indicators of lithium toxicity,” Kafantaris told Psychiatric News. “In this sample, the more common presentation of lithium toxicity was changes in mental status such as confusion, disorientation, or somnolence.”

Ott noted that the decision to use lithium rests on a trade-off between the mental health benefits and the risk of adverse somatic events. While he said that the study suggests “physicians should not withhold lithium for fear of intoxication in patients who benefit from it … physicians should have a low threshold to screen for toxicity if changes in mental and somatic status occur.”

The researchers concluded that to manage lithium treatment safely, clinicians should educate patients about the risks of lithium toxicity and help them understand the circumstances under which lithium levels can rise.

The study was supported by the Norrbotten County Research and Development Fund, Sweden. ■