A new drug for chronic insomnia

Effective natural remedies?

The virtues of valerian have been touted for a long time: “Beneficial effects have been observed, however we know that the placebo effect is very important when it comes to insomnia, notes Raphaël Heinzer, chief physician and director of the Center d investigation and research on sleep at the CHUV. But as long as the products consumed are not dangerous, so much the better if they bring a benefit to the patients. Synthetic melatonin, which mimics the effect of the hormone produced by the brain, can be useful especially in adolescents and adults over 55 years old. “This molecule does not cause addiction and little daytime sleepiness, specifies Stephen Perrig, neurologist-somnologist at the HUG Sleep Medicine Center. For those who have sleep disorders rather on the second part of the night, the so-called “delayed” forms are particularly interesting. Sleep disorders are a frequent complaint and represent a very lucrative market. It is therefore advisable to remain cautious in the face of the tempting promises of certain over-the-counter products, in particular on the internet.

Since last spring, the Quviviq® developed by the Swiss laboratory Idorsia has benefited from a sizeable communication campaign, although it has not yet been marketed in Switzerland. “I have patients who have done research on the internet and have already asked me if it was possible to obtain it”, illustrates Dr Stephen Perrig, neurologist-somnologist at the Sleep Medicine Center of the University Hospitals of Geneva (HUG). If Quviviq is so talked regarding, it’s because it offers a different approach to other drugs used for sleep disorders, with fewer side effects during the day and no risk of addiction. What arouse the interest of people whose sleep is disturbed. And they are numerous: 5 to 10% of the inhabitants of Western countries suffer from insomnia.

Clinical trials on 1800 people

“While benzodiazepines and sedative antidepressants target the neural processes involved in sleep, daridorexant, the active ingredient of Quviviq, acts on the vigilance circuits. It binds to orexin receptors, a neurotransmitter involved in wakefulness. By blocking its action, daridorexant promotes sleep,” explains Professor Raphaël Heinzer, chief physician and director of the Center for Investigation and Research on Sleep at the Center hospitalier universitaire vaudois (CHUV). This mode of action is similar to two other molecules, suvorexant and lemborexant, which are only available in the United States, Japan and Australia. “Many insomniac patients complain of hypervigilance, so this approach seems interesting,” comments Stephen Perrig, who however notes some limitations in the two clinical trials conducted on just over 1,800 people and published in the medical journal The Lancet Neurology¹.

The efficacy of the drug was assessed, once morest a placebo, using parameters measured during laboratory sleep recordings (polysomnography), before and following three months of treatment. “These are very objective parameters, but insomnia is on the contrary something very subjective: a parameter can be improved without the patient perceiving any better and vice versa”, explains Stephen Perrig. However, the researchers also assessed the feelings of the patients using a self-administered questionnaire. “It is a test that was created for this clinical trial and therefore has not been used to evaluate other therapies, so it is difficult to compare its relevance,” objects the doctor. In a comment published in The Lancet Neurology², doctors from the universities of Freiburg (Germany) and Oxford (United Kingdom) also point out that the items chosen in this questionnaire correspond more to an assessment of fatigue than drowsiness. The data also show that if the parameters measured are improved in patients who received daridorexant, the difference with patients receiving placebo is small.

Cognitive-behavioral therapy

“Even though they are widely prescribed, it is important to remember that drugs are not the first line treatment for insomnia. The reference treatment is cognitive-behavioral therapy (CBT)”, insists Raphaël Heinzer. If insomnia often begins on the occasion of an external disturbance (stress at work, divorce, accident, etc.), it is then frequently self-maintained by behaviors of which the patient is not always aware and that he must unlearn. The path to finding peaceful nights is sometimes surprising. “Some patients make the mistake of going to bed too early hoping that sleep will come more easily. On the contrary, we ask them to go to bed later and get up earlier in order to limit the time spent in bed. After a few days and a small debt of sleep, they find pleasure in going to bed and fall asleep more easily,” explains the doctor.

Insomnia is not a fatality and it is often possible to find a satisfactory sleep. However, relapses are not uncommon, specialists warn. The CBT makes it possible to identify the red flags which should alert the patient so that he resumes the tools acquired during the therapy. “Faced with occasional stress and to avoid falling back into a new vicious circle, having a well-tolerated “drug joker” such as daridorexant might be a plus”, suggests Stephen Perrig, who underlines the need for clinical evaluations for this type of therapeutic combinations.

Prevention from adolescence

Many adolescents experience a physiological shift in the sleep-wake rhythm that manifests itself in later bedtimes and rising. The use of smartphones in the evening can also create, or aggravate, this type of shift. Adolescence is also the time when academic pressure intensifies and stress can begin to manifest itself in troubled sleep. “Insomniac adults often report having had sleep problems from their teenage years,” notes Dr. Stephen Perrig, neurologist-somnologist at the HUG Sleep Medicine Center. This period is therefore a key moment to acquire the right reflexes for quality sleep. “To raise awareness among adolescents, we have initiated a “sleep week challenge“in a few pilot classes”, explains Prof. Raphaël Heinzer, head physician and director of the Center for Investigation and Research on Sleep at the CHUV. “The objective is to make them observe the impact of certain behaviors on their sleep and the benefits of better sleep on their quality of life.” After keeping a sleep diary for a week, the teens were asked to follow a week of tips for better sleep hygiene, including turning off smartphones at 8 p.m. better days.

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1. https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00436-1/fulltext

2. https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(22)00007-2/fulltext

Published in Le Matin Dimanche on 09/04/2022