CPCP: Valproate Hyperammonemic Encephalopathy by A Medical Student

Jessica Woelfel medical student
Jessica Woelfel medical student

Today we got an excellent Clinical Problems in Consultation Psychiatry (CPCP) presentation from medical student Jessica Woelfel, who is planning a residency in emergency medicine. It’s about valproate-induced hyperammonemic encephalopathy (VHE). This is a rare adverse event of Depakote, which is an anticonvulsant used in treating epilepsy and bipolar disorder. While it should be needless to say, it is critically important to make the correct diagnose of bipolar disorder before starting a complicated psychotropic medication treatment regimen because the medications used for treatment can have devastating side effects.

I think it’s worthwhile pointing out the diagnostic difficulty by quoting a knowledgeable resesarcher and clinician, Dr. Mark Zimmerman, MD. He’s the Director of Outpatient Psychiatry and the Partial Hospital Program at Rhode Island Hospital in Providence and the Professor of Psychiatry and Human Behavior at The Warren Alpert Medical School of Brown University in Providence, Rhode Island. Dr. Zimmerman has been conducting psychiatry research in assessment and diagnosis for more than 20 years, some of it early in his career at Iowa. He also has an excellent website on tracking outcomes in clinical practice. In the Summer 2016 issue of Psych Congress Network (Vol. 2, No. 1), a Q&A article by Eileen Koutnik-Fotopoulos entitled “Diagnosing and Treating Depression: What You Think You Know Might Not Be True,” here is his answer to the question “Regarding bipolar disorders, is overdiagnosis more common than underdiagnosis?”:

There has been a significant emphasis over the past decade to improve the recognition of bipolar disorder. Certainly, you would rather not miss a diagnosis of bipolar disorde, because there are potential negative implications. An individual [with bipolar disorder] should be treated differently. Also, by not recognizing bipolar disorder it could be associated with increased cost of care. There is the increased likelihood of prescribing antidepressant alone; thereby, the individual is at risk for switching from a depressive to a manic episode.

Clinicians, perhaps, have become so sensitized to not diagnosing bipolar disorder that they may diagnose it when the person doesn’t have bipolar disorder. I can’t tell you the number of charts I have reviewed of individuals who have  been diagnosed with bipolar disorder yet, when you’re looking for documentation of the manic or hypomanic episode, it’s lacking. I think the educational effort, the failure to follow the diagnostic criteria, and the availability of a pill to prescribe for bipolar disorder are all responsible for the tendency to overdiagnose the condition, and the primary diagnostic culprit responsible for overdiagnosis of bipolar disorder is borderline personality disorder. There are certainly some phenomenological similarities between the 2 disorders but they are also very distinct. It’s detrimental to the patient to be diagnosed with bipolar disorder when they have borderline personality disorder because it leads them down the wrong treatment path.

The rest of Dr. Zimmerman’s comments about depression are equally illuminating and I wish I could share them with you. There doesn’t seem to be an online version of the article although he’ll  be presenting at the U.S. Psychiatric & Mental Health Congress on these issues on Saturday, October 22, 2016 from 9:15 AM–10:30 AM, see the schedule.

On the same note, like Dr. Zimmerman, I can’t tell you how many times I’ve seen bipolar overdiagnosed over the last many years as well. There are medical disasters which can befall patients as a consequence, including but not limited to VHE.

Valproate-induced hyperammonemic encephalopathy can sneak up on both patients and doctors. The onset can happen even after years of treatment, as Jessica points out from her literature search. Careful history-taking, caution, skepticism, and a willingness to gather information about patients over longitudinal follow up are some of the ways clinicians can guard against harming patients with medications. We need to think about what we’re doing.

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