History of Mental Health 101: Chlorpromazine and the Drug Revolution

Foreword

History of Mental Health 101 is a set of articles that reviews the history of mental health from a sociological perspective: from the ancient to the modern understanding of the concept. Nowadays, mental health is one of the most widely discussed topics; however, it had a hard, alluring history of development through centuries. The following six articles explore the history of mental health and some of the most fascinating and sometimes unbelievable facts about the topic, aiming to raise awareness about mental health and its importance of one’s wellbeing.

1. History of Mental Health 101: Mental Illnesses and Demons

2. History of Mental Health 101: Is there a Healthy Mind in a Healthy Body?

3. History of Mental Health 101: The First Asylums

4. History of Mental Health 101: Chlorpromazine and the Drug Revolution

5. History of Mental Health 101: Deinstitutionalization and Comunity Care

6. History of Mental Health 101: Stigmatization of Mental Health

7. History of Mental Health 101: Mental Health in an Unequal World

Chlorpromazine and the Drug Revolution

The history of mental health is saturated with treatments and ideas that were often controversial. Civilization went through centuries of experimenting with different religious, mythological, or scientific methods on mental patients before adopting the right treatments and procedures. The most prominent changes happened during psychiatric revolutions in the late 1700s - and are still actively developing.

The First Psychiatric Revolution occurred in 1793 when Pinel introduced moral management in the asylums and started treating mental patients with care and consideration (Gelder et al., 2006). The Second Revolution in psychiatry took place in 1935, as a result of the invention of electroconvulsive therapy (ECT) by Cerletti and Bini (Saddock et al., 2009). ECT involves small electric currents being pressed through the brain to trigger a brief seizure: it alters the brain chemistry and can reverse symptoms of some mental problems. Nowadays it is done under anesthesia and is relatively safe; however, during early treatments, high doses of electricity were administered without anesthesia, harming patients, causing memory loss, fractured bones, and other severe damages (MayoClinic, 2018).

The Third Revolution of psychiatry occurred soon after World War II. It enabled treatment outside asylums and mental hospitals and was supported by the use of numerous drugs (Gautam, 2010). Introducing psychotropic agents in the treatments was a significant improvement in the process of curing mental health. It even awoke the hope to heal schizophrenia. In the middle of the discoveries was chlorpromazine, one of the most important of them, followed by anti-anxiety, antidepressants, antipsychotics, and neuroleptic drugs (Tyrer, 2008). They became the inception of the new field, psychopharmacology, which was developed between the years 1955 and 1970.

Figure 1: ECT can alter the brain chemistry and reverse some mental problems

There are two revolutions within psychopharmacology: the first psychopharmacological revolution involves introducing the drugs mentioned above into the treatments. Chlorpromazine was one of the most important discoveries in psychiatry, and like many other drugs, it was discovered accidentally by the French pharmaceutical company Rhône-Poulenc (Swazey, 1974) while conducting a study to explore phenothiazines for controlling worm infestations. Although the study failed, some of the phenothiazines proved to be efficient antihistamines (drugs that are used to treat allergies), and some others had effective anesthetic and sedative properties - later they were used successfully in sleep therapies (Caponi, 2020).

Chlorpromazine was further developed and studied by a French naval physician, Henri Laborit, who was exploring the implication of antihistamines as anesthetics for operations. (Rhône-Poulenc discovered it in the 1940s but there had not been any significant study to further explore this drug. Around 1950-1952 Laborit started studying it again). Most of the studies he conducted were frequently performed on animals, since it allowed researchers to examine isolated tissue, such as the brain and the whole body. As they claimed, it was impossible to conduct this kind of procedure on a human being without damaging the person’s health (Marston, 2013). Because of that, Laborit used trained rats that would respond to a physical threat, such as an electrified floor, by pressing an escape switch. “However, even when they knew the escape strategy to avoid an electric shock, the rats treated with compound 4560RP, later known as chlorpromazine, appeared insensible and completely unable to react” (Caponi, 2020). After a significant amount of tests and a sophistication of the medicine, Laborit started using chlorpromazine with his patients. Based on his observation, those patients that were given chlorpromazine demonstrated changes in their behavior; their sleeping pattern was improved by length and quality, they were calmer, and tended to lose consciousness less. After testing chlorpromazine on various mental problems and conditions, Laborit eventually suggested that it could have been used in the clinical psychiatry field. Moreover, he suggested chlorpromazine to be a surgery-free alternative for lobotomy (Caponi, 2020).

Figure 2: Henri Laborit

Apart from chlorpromazine, another decisive invention was Lithium, used for bipolar disorder. Lithium treatment was first introduced by John Cade as a cure for mania in 1949, but it was not approved by the U.S. Food and Drug Administration until 1970 (Ruffalo, 2021). It is worth mentioning Antidepressants were divided into two categories: Monoamine oxidase inhibitors and Tricyclic antidepressants. Both are still used in modern psychiatry and are known for influencing norepinephrine or/and serotonin in the brain. However, the results are more evident from one to two months of use, and the effects are not consistent (Rubin, 2019); thus, the perspective of treating depression or controlling florid symptoms of psychotic episodes in schizophrenia was a tremendous advancement in psychiatry and a hope for many mental patients and their families. Patients were allowed to lead fulfilled, normal lives out of the four walls of asylums and mental hospitals. Many mentally ill patients reported their symptoms to be absent, and those with serious diseases claimed that the deterioration of their health was slowed down thanks to the medicines (Marston, 2013).

After 60 years from those discoveries, the field of psychopharmacology is now entering a new phase. New Ketamine-based drugs, as Eugen Rubin writes, are promising a revolution in the field of psychopharmacology in terms of rapidity and their antidepressant effect (2019). The second stage of the psychopharmacological revolution will last approximately 15 years (2015-2030) and will alter psychiatry greatly.

For instance, for years Ketamine was approved as one of the most effective anesthetics, with an antidepressant effect in about an hour and a long-lasting effect (a week or more). In the second stage of the psychopharmacological revolution, new medications are being developed; the goal is to create new medications with faster and longer-lasting effects. For example, Esketamine was approved by FDA (U.S. Food and Drug Administration) to be an effective, fast treatment for treatment-resistant depression.

Figure 3: Ketamine

Another big improvement expected from the second psychopharmacological revolution is developing a new group of drugs, neurosteroids, that are different from the previous antidepressants in terms of structure and function. For example, one of the neurosteroids that have already been approved by the FDA is allopregnanolone. It is administered as a 60-hour intravenous infusion and is effective against postpartum depression (Rubin, 2019). Dr. Rubin also writes about a steroid called SAGE-217 which helps people suffering from depression to improve their mental health rapidly; however, more research is required before FDA approves this steroid as an antidepressant.

In conclusion, psychiatry went through a major drug revolution after World War II. The field of psychopharmacology improved between 1955-1970, and during those years, Chlorpromazine and various other drugs were developed that allowed mental patients to continue treatment at home - free from the asylums and brutal treatments. However, the field is still developing, and right now, psychopharmacology is going through changes that are promising faster and long-lasting results and stronger effects against some of the mental problems that people believe to be inevitable.

References:

• Caponi, S. (2021). On the so-called psychopharmacological revolution: the discovery of chlorpromazine and the management of madness. História, Ciências, Saúde – Manguinhos, Rio de Janeiro, v.28, n.3, jul.-set. Retrieved from: http://dx.doi.org/10.1590/S0104- 59702021000300003

• Gautam, S. (2010). Fourth revolution in psychiatry – Addressing comorbidity with chronic physical disorders. Indian J Psychiatry, 52(3), 213–219. https://doi.org/10.4103/0019-5545.70973

• Gelder M, Harrison P, Cowen P. (2006). Shorter Oxford Textbook of Psychiatry. 5th ed. New York: Oxford University Press Inc;

• Marston, H. (2013). A Brief History of Psychiatric Drug Development | Articles. Bap.Org.Uk. https://www.bap.org.uk/articles/a-brief-history-of-psychiatric-drug-development/

• MayoClinic. (2018, October 12). Electroconvulsive therapy (ECT). Https://Www.Mayoclinic.Org/. https://www.mayoclinic.org/tests-procedures/electroconvulsive-therapy/about/pac-20393894

• Rubin, E. (2019). The Second Psychopharmacology Revolution. Psychologytoday.Com. https://www.psychologytoday.com/us/blog/demystifying-psychiatry/201911/the-second-psychopharmacology-revolution

• Ruffalo, M. L. (2021, March 30). A Brief History of Lithium Treatment in Psychiatry. Psychiatrist.Com. https://www.psychiatrist.com/pcc/psychopharmacology/history-of-lithium-treatment-in-psychiatry/

• Saddock JB, Sadock VA, Ruiz P. (2009). Kaplan and Sadock’s Comprehensive Textbook of Psychiatry. 9th ed. Philadelphia: Lippincott Williams and Wilkins.

• Swazey, J. (1974). Chlorpromazine in psychiatry: a study of therapeutic innovation. Cambridge, MA: The Massachusetts Institute of Technology.

• Tyrer P, Silk KR. (2008). Cambridge Textbook of Effective Treatments in Psychiatry. 1st ed. New York: Cambridge University Press.

Image references:

• Figure 1: Brain MRI. (2016). [Ilustration]. https://images.app.goo.gl/6cKnue1yycbJAENKA

• Figure 2: Henri Laborit. Henri Laborit à propos de la perception de l'intelligence dans nos cultures. [Photograph]. https://www.rtbf.be/article/henri-laborit-a-propos-de-la-perception-de-l-intelligence-dans-nos-cultures-8983650

• Figure 3: Crawford, T. (2019). Ketamine [Photograph]. https://images.app.goo.gl/WY12hCdjdHUtw9GYA