December 11th, In 1951, in the laboratories of the French pharmaceutical company Rhône-Poulenc, chemist Paul Charpentier invented a drug that would change the field of psychiatry forever.
Charpentier had no intention of fomenting a revolution; in fact, he was trying to create a better antihistamine. But by modifying an existing drug called promazine, he ended up creating a new compound called chlorpromazine. The drug was given to a surgeon named Henri Laborie, who was looking for a more effective pain reliever. He noticed that it had a calming effect on his patients, and in 1952 Laborite persuaded colleagues at a military hospital in Paris to give the drug to a 24-year-old man suffering from psychosis. After twenty days of treatment, the man was ready “Resume normal life.” Although no one was sure how the drug worked, its popularity in the United States and Europe as a treatment for psychosis skyrocketed, leading to the neuroleptics known today.
Around the same time, drugs used to increase the release of the neurotransmitter dopamine, such as amphetamines, were found to cause psychotic symptoms. Researchers eventually found that drugs like chlorpromazine might work. suppression of dopamine transmission. Altering dopamine levels has become the cornerstone of schizophrenia treatment, laying the foundation for dopamine hypothesis of schizophreniaThe theory that dysregulation of the dopamine system causes symptoms of the disease.
Since the influx of discoveries in the mid-20th century, the field has not advanced much. The dopamine focus has led to neuroleptics becoming the classic treatment for schizophrenia. The drugs currently on the market do provide relief to many people living with this condition, but they have a bad effect on some patients and no effect on others and are notorious for causing unwanted and sometimes overwhelming side effects.
Unfortunately, the antipsychotic that works best for the symptoms of schizophrenia, clozapine, which appeared in the late 1980s, can have the most unpleasant side effects, including weight gain, diabetes, and excessive sleepiness. “It doesn’t work for everyone, but it’s just as effective and amazing as drugs,” says Ragi Girgis, associate professor of clinical psychiatry at Columbia University. Overall, the poor efficacy and notorious side effects of currently available drugs mean that a large percentage of people with schizophrenia simply stop taking their medication.
But the new drug gives hope to this area. Xanomelin-Tropium, or KarXT, has a new way to reduce dopamine transmission that promises to reduce symptoms as well as limit side effects. “The region has waited too long for something like this,” says Samir Jauhar, a London-based psychiatrist and lecturer in affective disorders and psychoses at King’s College London. “I think this is a breakthrough,” says Christoph W. Correll, professor of psychiatry at Hofstra University in New York. “We have been waiting for a new mechanism of action for 70 years.”
While dopamine appears to play a key role, the very thing that causes schizophrenia affects roughly 24 million people around the world remains elusive. But the need for more effective treatments is clear. The disease is one of the main causes of disability worldwide: One of 20 people with schizophrenia commit suicide, oh 80 percent leave work, and this shortens the lives of affected people by one to two decades.