"Normal" Serum Lithium Levels Might be Neurotoxic in Geriatric Bipolar Disorder

Marlene Busko

March 20, 2008

March 20, 2008 (Orlando, Florida) — In a study of bipolar patients treated with lithium, serum lithium levels did not correlate with brain lithium levels in older patients. In addition, higher brain lithium levels, but not higher serum lithium levels, predicted greater executive dysfunction and somatic symptoms of depression in older subjects.

These findings, by Brent P. Forester, MD, from the McLean Hospital in Belmont, Massachusetts, and Harvard Medical School in Boston, Massachusetts, and colleagues, were presented in a poster here at the American Association for Geriatric Psychiatry (AAGP) 2008 Annual Meeting.

"When you are treating an older patient with bipolar disorder who has been on lithium and they're having subtle signs of attentional problems (that look like mild delirium or confusion), even if their serum level is 0.6 or 0.8 [mEq/L], which would be 'normal' in a younger person, it might actually be quite toxic in an older person," Dr. Forester told Medscape Psychiatry.

There is no reason to take older bipolar disorder patients who are mildly lithium neurotoxic off this medicine completely if their kidneys are functioning well, he added. Clinicians need to take a step back and say, "Maybe the patient just needs a lower dose and they'll be fine," and not just rely on serum levels to make these decisions, he said.

Lithium remains one of the first-line treatments for mania in older adults, despite the lack of randomized controlled trials of this drug in this patient population, the group writes. Concerns about neurotoxicity have led to questions about the most effective way to use lithium safely in older adults with bipolar disorder.

The clinical practice of monitoring serum lithium levels is based on the assumption that serum levels linearly correlate with the amount of lithium in the brain. However, in the elderly, this relation might be more variable.

The group aimed to examine the relation between brain and serum lithium levels in adult patients with bipolar disorder and to look at the effects of lithium on neuropsychological functioning and mood in a group of older patients.

The study enrolled 26 subjects, aged 20 to 85 years, who had bipolar disorder and were currently being treated with lithium. The subjects included 16 younger patients (less than 50 years; mean age, 29.3 years) and 10 older patients (50 years or older; mean age, 65.3 years).

The mood of each subject was assessed using the Hamilton Depression Rating Scale and the Young Mania Rating Scale. Frontal lobe executive functioning was determined in the older subjects using the Stroop interference test, the Trail Making Test (part A), and the Wisconsin Card Sorting Test.

Serum and brain lithium levels were obtained for all subjects. Brain lithium levels were measured using 7-lithium magnetic resonance spectroscopy, a test that is used in research but is not available in clinical practice, said Dr. Forester.

Breakdown in Serum to Brain Lithium Relation in Older Adults

Brain lithium levels correlated with serum lithium levels in young subjects, but this correlation was not present in the older subjects.

In the older subjects, higher brain but not serum lithium levels correlated with higher Hamilton Depression Rating Scale scores and with an increase in somatic symptoms (fatigue and gastric distress). Higher brain lithium levels in these older patients also had a significant adverse effect on the Stroop interference test and on perseverative errors on the Wisconsin Card Sorting Test.

Age-associated changes in the blood-brain barrier might alter lithium uptake into the brain, the group suggests.

In older adults with bipolar disorder, clinical monitoring of serum lithium alone, without an assessment of cognitive functioning, might not be an adequate predictor of neurotoxicity, and clinicians should consider lithium toxicity when confronted with a depressive syndrome in such patients, they write.

This study provides further insight into lithium dosing in older patients with bipolar disorder, said Dr. Forester. "We're trying to learn how better to use this medicine because it's highly underutilized these days. It still has a lot of benefits."

The researchers have disclosed no relevant financial relationships.

American Association for Geriatric Psychiatry 2008 Annual Meeting: Poster 6. March 14-17, 2007.

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