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Tardive Dyskinesia: Finally Some Good News

Tardive Dyskinesia: Finally Some Good News

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From the Editor

By now, nearly every one of us is sick of trying to decipher the recent news reports for veracity. But fear not, here’s one that is guaranteed to be true. Just a few weeks ago, the FDA approved valbenazine (to be marketed as Ingrezza by Neurocrine Biosciences) as the first treatment specifically indicated for tardive dyskinesia (TD).1

Those of us who came into psychiatry some decades ago, before the advent of the newer generation of antipsychotic medications, with their putative lower risk, were trained to be particularly vigilant for TD. We were taught that this severe adverse effect of first-generation drugs was possibly reversible if caught early enough, but most often was irreversible. Among the severe adverse effects of antipsychotics, neuroleptic malignant syndrome (NMS), thankfully rare, can be acutely fatal in about 10% of cases.2 Aggressive, rapid intervention is needed to treat this severe problem.

Movement disorders—a more common adverse effect of antipsychotics—have, as you know, 2 major types. Akathisia, a generally reversible movement disorder with primarily extrapyramidal symptoms, is treated—other than by discontinuation or reduction of the dosage—primarily by using benztropine, which may be preventive in some cases; propranolol; clonidine; or one of several benzodiazepines.

We’ve been waiting since 1953, the year chlorpromazine was introduced to the US as a revolutionary treatment for schizophrenia, for an active treatment for tardive dyskinesia that the FDA judged to be effective.

While less severe than the other 2 major adverse effects mentioned here, akathisia is extremely uncomfortable. I had a brief case back in my 30s when I was treated with Phenergan for a severe GI viral infection and had become quite dehydrated. I assure you that even though we consider this to be a relatively less severe effect than TD or NMS, the level of discomfort would be difficult for anyone to tolerate for more than a brief period.

When the newer generation of antipsychotics was introduced, the marketing folks trumpeted the news that worries about most movement disorders were a thing of the past. Of course, as we learned soon enough, that turned out to be fake news.

No one has yet been able to discern the specific etiology of TD, although it is thought to be related to long-term, at times quite brief, exposure to dopamine receptor blockers such as the antipsychotic medications we all use. Valbenazine is described by Neurocrine as a selective vesicular monoamine transporter 2 (VMAT2) inhibitor. I’ll leave further detailed discussion of the pharmacology of this medication to those far more expert than I am in future Psychiatric Times reports. It should already be on the market by the time you are reading this. Of course, it isn’t cheap, folks, much like many recent breakthrough medications, with an annual cost likely to be in the tens of thousands of dollars.

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