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Switching Elderly Bipolar Patients From Lithium To Valproic Acid Questioned

There has been a marked shift for prescribing valproic acid over lithium carbonate for elderly patients with bipolar disorder who live in Ontario, Canada, despite the absence of evidence based data.

This shift is highlighted in a study by Dr Kenneth Shulman and colleagues at the Department of Psychiatry, Sunnybrook and Women's College Health Sciences Centre, University of Toronto. Lithium has been the mainstay in the past for the management of bipolar disorders for all age groups, and elderly patients pose a special concern because of the potential for toxicity.

The evidence for the superiority of valproic acid in treating bipolar disorders -mixed episodes and rapid cycling - has been challenged in a recent Cochrane review, the clinicians point out. Because of the rise of valproic acid (prescribed as divalproex in North America), the clinicians used provincial agency data to identify residents over the age of 65 who had taken lithium or valproic acid over an 8 year period, as well as those who had not previously taken the drugs. Data from a second agency helped them distinguish between psychiatric and anticonvulsant uses of lithium and valproic acid, and between bipolar disorder and other indications such as dementia.

Dr Shulman and colleagues identified 3,902 patients who had no previous history of convulsive disorders who were started on lithium, and 5, 341 patients who were started on valproic acid. New valproic acid users were slightly older (75.4 years) than lithium users ( 73.5 years).

More than 75% of new lithium users, and fewer than 66% of valproic acid users, had contact with a psychiatrist. Almost 25% of the new lithium patients, and 41% of new valproic acid patients, had had a diagnosis of dementia.

Before lithium is abandoned for certain patients, "adequate evidence that valproic acid offers a comparable or superior efficacy, effectiveness, and safety profile is needed," say Dr Shulman and colleagues. "Indeed, the concerns about lithium toxicity may reflect a failure to adjust for pharmacokinetic and pharmacodynamic factors that occur in old age."

They conclude: "Given the complexity, morbidity, and mortality associated with bipolar disorders and dementia in elderly patients, the use of mood stabilisers and other psychotropic agents requires ongoing systematic evaluation."
BMJ 2003;326:960-961.

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