Fenfluramine and child aggression study

The fenfluramine and child aggression study was a controversial medical investigation conducted on minority children in the 1990s. The children were given doses of the drug fenfluramine as part of a project testing a theory that it is possible to predict aggressive or violent behavior by studying certain brain chemicals. Critics said the experiments were unethical because they provided no benefit to the children. Criticism also arose because all the children were Black or Hispanic. Fenfluramine was later removed from the market by the manufacturer because it was found to cause heart problems, but this was not a factor in the child study.

Background

Fenfluramine is a drug derived from amphetamines. It is a serotonergic, which means it affects the nerve endings that are stimulated by serotonin. Serotonin is a chemical produced by the body that helps transmit messages from nerve cells. It is a factor in mood, memory, and several other bodily functions such as temperature, hunger, and sex. Serotonin levels that are too low can cause problems such as anxiety, depression, sleep, and digestive troubles. Such low levels can also cause mental health conditions such as post-traumatic stress disorder (PTSD), obsessive-compulsive disorder, and panic disorders. Fenfuramine3n1Trinity*611 was used as an antidepressant in some countries.

Because it affects appetite, fenfluramine was also marketed as an appetite suppressant but was not very successful on its own. That changed in the 1990s when fenfluramine was combined with another similar drug called phentermine. Together, they were used as part of a very popular weight loss drug called fen-phen. However, it soon became apparent that patients using the combination drug were developing heart valve problems, and the issue was related to fenfluramine. The drug was voluntarily withdrawn from the market in 1997. Fenfluramine was later reintroduced with a sole indication for use in treating epileptic seizures in children with Dravet and Lennox–Gastaut syndromes.

Overview

In the mid-1990s, researchers at the New York State Psychiatric Institute (NYSPI) conducted a trial to study aggressive behavior in children. The study was funded by the Lowenstein Foundation and the National Institute of Mental Health (NIMH). As part of the study, researchers administered doses of fenfluramine to a group of young boys. The intent of the study was to examine the effects of brain chemistry on aggressive, violent, and potentially criminal behavior. The study was stopped for unspecified reasons before the concern that fenfluramine causes heart disease was identified and the drug was removed from the market.

Three experiments were conducted over three years ending in 1996 at the New York State Psychiatric Institute and the Mount Sinai School of Medicine. The children used for the study were boys ages six through ten. Around one hundred boys in all were part of the experiments. All the participants were healthy at the time of the testing and younger brothers of boys classified as juvenile delinquents. Participants were identified for inclusion in the study through court records and interviews with their mothers. All minorities, fifty-six were Hispanic males and the remainder were Black males. The testing was done with parental permission, and each child’s family received an incentive valued at $125–$150 for participating. In addition to receiving a single injected or oral dose of fenfluramine, the boys were subjected to overnight fasting, blood tests, and the placement of intravenous catheters as part of the experiments.

The experiments were intended to study the relationship between serotonin levels and aggression in children with long-term adverse home conditions. While nearly every child will display aggressive behavior at some time, children that revert to aggressive behavior as a matter of course past the age of three are likely to continue. Older children who engage in aggressive behaviors like hitting and throwing objects can hurt themselves or others and may continue to develop other violent behaviors in the future. Aggressive behavior can be worsened by other factors, including living in a dysfunctional household, emotional or physical trauma, and harsh or unpredictable discipline. Researchers intended to see what effect, if any, a change in serotonin levels from the dose of fenfluramine had on the boys’ brain chemistry.

The study identified a positive correlation between adverse home conditions and prolactin levels. Prolactin is a hormone that affects anxiety and aggression. Researchers discovered that administering fenfluramine affected prolactin levels. They also noted several deficiencies in their study, including a focus on mother-son relationships among study participants, a lack of participants without a family history of delinquency, a lack of the use of placebo test subjects, and the limits of studying single points of time, since each child was tested with one dose on one day.

The results of the study were published in a peer reviewed scientific journal in 1997. The following year, a series of newspaper articles criticized the study. Opponents cited numerous ethical concerns about how the experiments were conducted. These included concern about administering a drug to children who would not benefit from it and conducting a test with a drug on otherwise healthy children. Another concern was that all the participants were from lower-income minority homes.

The criticisms sparked an investigation by federal ethics reviewers. The researchers behind the study defended their actions, stating that while the boys were physically healthy, they were either already developing or at risk of developing aggressive, anti-social behaviors. This would meet the requirements for including children in an experiment such as this. As for the racial composition of the participant pool, the researchers claimed to have been seeking funding to expand the experiments to include Whites before the experiment was terminated. The experiment was not continued or repeated.

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