Some drugs for ADHD may increase psychosis more than others

AAdolescents and young adults treated for attention deficit hyperactivity disorder may present a higher risk of psychotic event if they receive amphetamine-based drugs. , such as Adderall and Vyvanse, instead of drugs based on methylphenidate compound, such as Ritalin or Concerta, according to a study released Wednesday.

According to the study published in the New England Journal of Medicine, the risk of psychosis was generally low and only concerned one in 660 patients.

The risk is "low enough that you can not say," do not just prescribe Adderall, "said Dr. Lauren Moran, the lead author of the study. "But from a public health perspective, these drugs are prescribed to so many millions of people that thousands of people are more likely to suffer from psychosis." Moran is an assistant professor at Harvard Medical School and a psychiatrist for hospitalized schizophrenics . and bipolar patients at McLean Hospital.


It is unlikely that the study will affect the drugs used in most cases, but it could lead physicians to look more closely at the potential risk factors for other mental illnesses when prescribing ADHD medications. The method of data collection should also be noted: researchers used "real world evidence", a term that refers to data collected during medical practice and not in the gold standard of controlled clinical trials randomized.

The study was conducted with Aetion, a New York-based health data firm founded by another Harvard researcher. Moran has no financial relationship with Aetion.

"I do not think it's a shocking conclusion," said Dr. Anthony L. Rostain, professor of psychiatry and pediatrics at the Perelman School of Medicine at the University of Pennsylvania. He mentions in the instructions accompanying any stimulant prescription a low risk of psychosis. "It will be simply important to mention to people that amphetamine-based compounds pose a slightly higher risk … I think the return home should be to inform everyone before starting a drug the risks such that psychosis. "Rostain was a consultant for Shire, who sells Vyvanse and developed Adderall; This company is now part of the Japanese drug giant Takeda and another manufacturer of amphetamines, Arbor Pharmaceuticals.

The study used a database of insurance claims – care notifications received by patients that are used by the payment system – that was assembled by Aetion. The study began by looking for patients aged 13 to 26 years who were diagnosed with ADHD and started taking methylphenidate or amphetamine between January 2005 and September 2015. It revealed that 110 923 people had received each type of drug that could be compared based on age and other risks. factors. Patients with signs of existing psychosis, such as a prescription for an antipsychotic drug, have been excluded.

The researchers then examined whether each patient had been diagnosed with psychosis severe enough to warrant antipsychotic treatment within 60 days. In this group, there were 343 episodes of psychosis, 106 in the methylphenidate group, a rate of 0.1%, and 237 in the amphetamine group, a rate of 0.21%. Amphetamine users had a 65% increase in the risk of a psychotic event, which could include delusions or hallucinations.

Moran and Rostain both said that differences in how drugs work in the brain could be one of the reasons for this difference. Both increase the levels of neurotransmitter dopamine, which is involved in a multitude of brain functions. Methylphenidate works by preventing dopamine from being eliminated from the brain. Amphetamines, on the other hand, prevent the elimination of dopamine and increase the production of dopamine. They also noted that one of the risk factors for psychosis is drug use other than by excessive consumption. Rostain noted snorting amphetamine pills as a potential risk.

Moran began to be interested in the issue because she had young patients, most of them old enough to attend university, who presented themselves in her inpatient psychosis consulting service. after using stimulants. She first directed the project as part of a course taught by Sebastian Schneeweiss, professor of medicine and epidemiology at Harvard Medical School and key adviser to Aetion. The results were so intriguing that they decided to tackle them as a larger and more rigorous study.

Schneeweiss said in an interview that Aetion had been founded because of a "huge demand for hard evidence coming close to the cause-and-effect conclusions" and that such an effort, which required engineers to well-paid software, could not have ended up in Harvard. The company is working with the Food and Drug Administration to determine if its databases can replicate the results of randomized trials, which randomly assign patients to one treatment or another. Aetion's software platform, he said, is "transparent with audit trails with all the features required by regulators to make regulatory decisions based on these studies." Aetion has raised a total of $ 77 million from investors such as McKesson Ventures, Sanofi and UCB, according to Pitchbook.

Moran and Schneeweiss said the next step will be to conduct further studies to help doctors identify patients most at risk for psychotic episodes.

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