The new anti-insomnia pill that won’t end the pandemic of sleep disorders

Daridorexant, recently approved in Europe, is safe, has few side effects and does not create tolerance or cause drowsiness the next day, but it is not the solution to sleep troubles

Daridorexant insomnia Europa
Chronic insomnia affects between 6% and 12% of European population.FERNANDO HERNÁNDEZ / Getty

During the years of Nazism, when willpower was extolled above all, there was a boom in drugs to control the affliction that affects even the strongest of us: lack of sleep. Pervitin, a stimulant in the methamphetamine family, kept young Germans awake for days during the Blitzkrieg. Hitler consumed all kinds of substances to keep himself alert and euphoric during the day, but he soon realized that manipulating a mechanism as complex as sleep had costs. At night, he suffered from insomnia. His doctor, Theodor Morell, gave him tranquilizers to help him sleep. In the morning, he was injected with stimulants again to compensate for the drowsiness caused by the drugs from the night before.

Attempts to control sleep continue today. Amphetamines like pervitin are not legal without a prescription, but coffee, a tool for maintaining productivity at the cost of adequate rest, is the most widely used drug on the planet. And on the other side of our fight against sleep, the use of benzodiazepines, created to combat anxiety but often used against insomnia, is growing steadily in Europe. In countries including Spain, Portugal and the United Kingdom, around 100 daily doses are taken for every 1,000 inhabitants.

The study of the biological basis of sleep has offered some pharmacological alternatives to existing substances with significant side effects. A few days ago, the European Commission authorized the sale of daridorexant, a drug aimed at adults with chronic insomnia, which affects between 6% and 12% of the European population. The drug blocks the activation of orexin receptors, a type of hormone that maintains wakefulness. In an article published in the journal The Lancet Neurology, the drug is presented as a safe sleeping pill, which induces sleep, maintains it throughout the night and does not cause drowsiness the next day. It also does not generate tolerance, which can make many drugs lose effectiveness with use.

Odile Romero, coordinator of the Sleep Unit at the Vall d’Hebron Hospital in Barcelona, has participated in clinical trials with the drug and believes that the experts are keen “for it to be marketed, because the studies offer very high positive expectations, and no new treatments have appeared for years.” In her opinion, after studies of up to a year, it has been shown “that it is not necessary to increase the dose over time and dependence is not generated” and that “there is no rebound effect [and greater drowsiness] when you stop taking the drug.” Milagros Merino, president of the Spanish Sleep Society, also considers daridorexant a positive addition to the arsenal of insomnia treatments, especially because “until now, the treatments used were not based on the pathophysiology of insomnia.” This new drug “allows direct impact on orexin, a neurotransmitter that maintains wakefulness.”

“If you don’t sleep well, it’s because something is wrong. The problem of modern society is stress, and insomnia is a response to that”
Luis de Lecea, Stanford University

The new drug also shows how the study of basic biology ends up, over time, having practical applications. Orexins were discovered in animal models more than two decades ago by two researchers simultaneously. One of them is the Spaniard Luis de Lecea, head of the Department of Psychiatry and Behavioral Sciences at Stanford University. De Lecea, who has consulted for the company that has developed the drug but has not participated in the trials, says that the results are good. “Waking up in the middle of the night is avoided, because it has a fairly long half-life, but it does not leave you groggy the next day, as happens with benzodiazepines,” explains De Lecea.

Chemical structure of the active ingredient of the new drug.

If daridorexant has no or minimal side effects, if it doesn’t build tolerance and if it leaves its users full of energy the next day, you might wonder why we shouldn’t all take it every time we have trouble falling asleep. De Lecea insists that the studies behind the drug are reliable, but notes that long-term side effects cannot be ruled out. In any case, he says, “interfering with sleep has consequences.” “If you don’t sleep well, it’s because something is wrong. The problem of modern society is stress, and insomnia is a response to that,” he says.

The Stanford researcher states that “the number of people with sleep problems reflect a brutal epidemic.” “Sleep problems bring additional problems with depression, the immune system or susceptibility to being overweight,” he says. In his opinion, insomnia should be treated as a public health problem, with a reflection on what causes us stress: our obsession with productivity and growth, work schedules and the use of electricity. “A pill is not a collective solution, and we cannot ask for society to be constantly drugged,” he concludes.

“Nobody would think of asking a relative how to treat diabetes, but it happens with sleep”
Milagros Merino, president of the Spanish Sleep Society

Despite being a social problem, insomnia is treated as a private issue. More than with other ailments, people go to family or friends in search of solutions. Self-medication is common. “Nobody would think of asking a relative how to treat diabetes, but it happens with sleep,” says Merino. “Those of us who do sleep medicine believe that all products given for sleep should be regulated like medicines and prescribed by specialists, and we must raise awareness so that people do not self-medicate,” he adds.

He explains that the use of daridorexant and other sleep drugs should be considered progressively, taking into account the options that already exist, “because it will come out with a higher price than what we use now.” “There are some action protocols. It’s like with pain. It goes from less to more. You don’t start with morphine derivatives,” he says. In fact, currently, the first line for severe insomnia is cognitive behavioral therapy, a treatment that is sometimes combined with drugs but requires specialists who may not be as affordable.

Odile Romero agrees on the need for a change of mentality in the population. “There is still talk of taking advantage of time to do more things and sleep less. There is a lack of social awareness, as in the past with diet or exercise, that a well-slept population is a healthier population with a better mood,” she states. New drugs such as daridorexant, based on a deeper understanding of sleep mechanisms, will be much more effective in treating insomnia than self-medication with benzodiazepines. But in the long term, sleep should stop being something to regulate with chemicals, understood rather as a pillar of physical and mental health. Like adequate rest, such a shift depends on collective changes in the shape of our society.

More information