The drug for schizophrenia finally gets an overhaul

On December 11, In 1951, in the laboratory of the French pharmaceutical company Rhône-Poulenc, chemist Paul Charpentier concocted a drug that would change the field of psychiatry forever.

Charpentier had no intention of sparking a revolution; he’s actually trying to make a better antihistamine. But by tweaking an existing drug called promazine, he eventually created a new compound called chlorpromazine. The drug was passed on to a surgeon named Henri Laborit, who was looking for a more effective anesthetic. He found it to have a calming effect on his patients, and in 1952 Labourit convinced colleagues at a military hospital in Paris to give the drug to a 24-year-old man with a mental disorder. . Twenty days of treatment, the man is ready “to carry on with a normal life.” Although no one is sure how the drug works, its popularity has exploded across the United States and Europe as a treatment for psychosis, spawning antipsychotics like them. known today.

At the same time, it has been found that drugs used to increase the release of the neurotransmitter dopamine, such as amphetamines, can lead to the appearance of psychotic symptoms. Researchers have eventually discovered that drugs like chlorpromazine can work by decrease the transmission of dopamine. Altering dopamine levels has become the cornerstone of schizophrenia treatment, laying the groundwork for The dopamine hypothesis of schizophrenia—theory that the dysregulated dopamine system causes the symptoms of this condition.

Since many discoveries in the mid-20th century, the field has not progressed much. The focus on dopamine has made antipsychotics the classic treatment for schizophrenia. Medications currently on the market achieve some degree of remission for many people with the condition, but they work poorly for some patients, have no effect on others, and are notorious for being cause unwanted and sometimes too severe side effects.

Frustratingly, the antipsychotic drugs that work best against the symptoms of schizophrenia—clozapine, which emerged in the late 1980s—can cause the most serious side effects, including weight gain, diabetes, and excessive sleepiness. “It doesn’t work for everyone, but it’s as effective and wonderful as the drug,” says Ragy Girgis, an associate professor of clinical psychiatry at Columbia University. Overall, the low efficacy and notorious side effects of currently available drugs mean that a large proportion of people with schizophrenia simply suffer from schizophrenia. stop taking their medication.

But a new drug is bringing hope to the field. Xanomeline-trospium, or KarXT, has a new way to reduce dopamine transmission that holds promise for alleviating symptoms while limiting side effects. Sameer Jauhar, a psychiatrist in London and a lecturer in affective and psychotic disorders at King’s College London, said: “The field has been waiting for something like this for too long. “I think it’s a breakthrough,” says Christoph U. Correll, a professor of psychiatry at Hofstra University in New York. “For the past 70 years, we have been waiting for a new mechanism of action.”

While dopamine seems to play an important role, what exactly causes schizophrenia affects 24 million people worldwide, remains elusive. But the need for better treatment is clear. This condition is one of the leading causes of disability worldwide: one in 20 people with schizophrenia take their own lives, about 80 percent quit, and it cuts short the lives of those affected by one to two decades.


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