The myth of therapeutic ranges for Lithium and Depakote in psychiatric disorders

In medicine we often operate on assumptions that have all the trappings of science, but are in actuality untested conventions. Sometimes these conventions get so much legitimacy that we believe we are practicing top notch evidence-based science while in reality we are harming our patients.

One such convention is the belief that lithium's therapeutic range is between 0.5 to 1.5. This convention receives so much currency that clinical labs across the world give it as the standard normal range. In reality many patients, especially aggressive developmentally disabled ones, show good response to lithium levels well below the recommended 0.5; ironically, when their levels are pushed higher into the so designated 'therapeutic range', they show subtle cognitive and neuromuscular problems.

It is not uncommon for me to receive a request from a patient's Primary Care Physicians (PCP) to increase his lithium dose because the blood level is below the therapeutic range. Requests are received only if the smarty-pants doctor has not already gone ahead and raised it, convinced he knows more than a psychiatrist on how to medicate mental patients. This high-handedness often happens in the ERs as well, where the ER doctors, unilaterally change the dose of psychiatric medications, going just by what they know about therapeutic ranges as given in their lab reports.

Bipolar patients appear to be special target for overmedication. The drug most often used with them, Depakote, it's therapeutic range is believed to be between 50 to 150. I have always wondered why the range spreads so neatly between 50 and 150, with 100 as the dead center. With 50, 100, and 150 being such perfect numbers, God was really acting the mathematician when forging the treatment of Bipolar Disorder. Could that perfect spread be an unconscious plagiarism of the lithium therapeutic range having been declared as 0.5 to 1.5, if one ignores the decimal points?

Once, world-famous Dr. Charles Nemeroff came to Detroit to a Marriott Hotel at the behest of Depakote company. We were each paid $500.00 (in addition to an eye-popping spread of breakfast, lunch, and a range of exquisite wines) to listen to him and his buddy, Dr. Henry Nasrallah. Drs. Nemeroff and Nasrallah rebuked the gathering for not diagnosing enough people as Bipolar. In addition, they further rebuked, that those who do get diagnosed as Bipolar even they do not receive enough Depakote to keep their levels north of 100. When I expressed concern that everybody and his mother is getting diagnosed as Bipolar, and the ideal therapeutic point of 100 sounds outright fishy, and was probably arbitrarily chosen because 100 is a sexy number, I received the dirtiest possible look that could be given by a platform performer.

Like with lithium, Depakote seems to work quite well for many patients at dosages well below what it touted as its therapeutic range. While unnecessarily high dosages of Depakote does not do too much harm beyond making profits for drug companies and their hired-hand doctors, and occasional liver failure, high lithium levels for prolonged periods do serious damage to kidneys.

Over the years I have seen many patients developing renal failures because their doctors kept their lithium levels around 1, or higher, without ever testing whether they could be managed at lower levels.

Of course, some patient do require therapeutic levels of 1 or even slightly higher, and I'm not recommending that such patients have their lithium levels lowered and be subjected to possible relapse. But, in my clinical experience rarely does a patient require lithium levels above 1.1 and many patients do well on levels below 0.5. Even those who require lithium levels above 1.0 during acute mania, the psychiatrist should be ever alert to lower it once his mood stabilizes.