History of Medicine

A Brief History of “Off-Label” Use of Amytal in Psychiatry

In my AMS funded scholarship I investigated published medical and psychiatric cases of uses amytal in an “off label”, published 1920 – 1950. In order to reconstruct a “label” of uses, I recorded successive versions of pharmacology textbooks. By reviewing Goodman and Gillman’s The Pharmacologic Basis of Therapeutics, I was able to learn conditions which the medical profession broadly considers “efficacious”.

By studying these cases, we can further understand firstly the history of catatonia, an elusive figure in the history of psychiatry, and how effective therapies can be missed. This project also provides some insight about the effects of label/off label on physician practice.

While psychiatric medications are now central to psychiatry and psychotherapy, prior to the advent of barbiturates, talk therapy, popularized by Sigmund Freud, was the primary form of clinical psychiatric treatment. In the early 1930s, American neurologist and psychiatrist William Bleckwenn used sodium amytal to render catatonic patients responsive so that he could conduct patient interviews and engage in talk therapy. Bleckwenn found a new, “off-label” use for this anaesthetic and anxiolytic medication in psychiatry. A drug previously used to sedate patients could now be used to facilitate treatment. So-called “off-label” uses of medications pioneer new pharmacotherapeutic pathways in medicine. It may be that current strictures against off-label prescribing are over-prescriptive and close off innovative new uses. Early treatment of catatonia with barbiturates provides insight into the events, processes, reasoning, and clinical practices that pushed psychiatry out of the chaise lounge and into the pharmacy.

Today, medications are central to psychiatry; prescribing privileges are a distinguishing feature separating psychiatry from psychology. While both psychiatrists and psychologists can administer talk therapies, only psychiatrists and licensed physicians prescribe medications for mental illnesses.

In Pharmacotherapy of mental illness – a historical analysis, Thomas Ban identifies hypodermic injection of morphine, which emerged in 1855, as one of the first medications used in psychiatry (Ban, 2001). Initially, drugs were introduced to psychiatry as a means of sedation and control. The barbiturate class of medications gained popularity as a chemical restraint. The first barbiturate, barbital (better known by its trade name, Veronal) was synthesized by Fischer and Von Mering in 1903 (Ban, 2001; Brunton, Knollmann, & Hilal-Dandan, 2018). While barbiturates were being used for a number of common indications (sedative, hypnotic, anaesthetic), some clinicians were experimenting with their utility in different clinical situations. These “off-label” uses of medications were an important mechanism by which physicians expanded the domain of clinical medicine and learned more about diseases.

In 1930, William Bleckwenn’s “off-label” usage of Sodium Amytal led to the discovery that, in small doses, the drug allowed otherwise totally unresponsive patients with catatonia to be free from their stupor (Bleckwenn, 1930). This discovery was soon further developed by psychiatrist Melvin Thorner, whose patients could now temporarily answer questions and provide insights into their condition (Thorner, 1935). This combination of psychodynamics and pharmacotherapy allowed for new insight into catatonia as a psychiatric condition.

The 1990 film Awakenings contains a popular depiction of a similarly startling case. Robin Williams plays a fictionalized version of Dr. Oliver Sacks, a British neurologist who discovered that the drug L-Dopa, could be used to temporarily “wake up” his patients with severe parkinsonism in 1969. Before this treatment these patients were equally inaccessible as those with catatonia which Bleckwenn, Thorner, and others have treated with amytal.

The off-label use of Sodium Amytal indicates a shift in psychopharmacy. Drugs became a form of treatment, not just sedation. In this case, drugs became necessary to make the end goal of talk therapy possible. Bleckwen’s innovation and methodology reminds us of early psychiatry’s tolerance for experimentation.

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