Why is Brazil experiencing an epidemic of zolpidem abuse? | Drauzio Varella

The medication has a high potential for dependence and its abrupt suspension can even lead to convulsions.

Zolpidem, a medicine used to treat insomniaarrived in Brazil in the mid-1990s. At that time, it was sold as a faster, more efficient solution with less potential for abuse compared to benzodiazepines, until then the most used in the treatment of sleep disorders. After almost 30 years, however, the country found itself immersed in what many doctors call the “drug Z epidemic”.

In an interview for this report, a specialist reports cases of patients who became dependent on the medication and took between ten and 56 pills a day, much more than recommended. According to the leaflet, adults under 65 should only take one tablet a day, equivalent to 10 mg, always under medical supervision. In studiesthere are reports of people consuming even higher doses, between 170 and 240 tablets over 24 hours.

Zolpidem can be addictive because it has a short half-life, according to doctor Roberto Ratzke, professor of psychiatry at the Federal University of Paraná (UFPR) and clinical director of Heidelberg Hospital, in Curitiba. Half-life refers to the time it takes for a medication to eliminate 50% of its dose from the body. “The shorter and faster the effect, the less time it stays in the body and the more addictive it is. That’s why cocaine and crack are so addictive,” he says.

The medicine begins to induce sleep between 15 and 30 minutes after ingestion. Therefore, the person undergoing treatment should take it moments before going to sleep, close to the bed. The effect occurs because the medicine binds to the GABA receptor (gamma-aminobutyric acid), the main inhibitory neurotransmitter (chemical messenger that transmits information) of the central nervous system, causing a decrease in consciousness. Alcohol also connects to this same neurotransmitter.

According with the doctor. Ratzke, zolpidem should be used for short periods of no more than three or four weeks, specifically for insomnia. In some more serious cases of the condition, he explains, treatment could last a few months, always with professional monitoring. But people started using it for prolonged periods, generating dependence, and for purposes other than insomnia.

As the medicine also promotes an unwanted effect of anxiety relief and well-being, many people started taking the medicine before meetings, presentations and even as a recreational drug.

See also: Is it insomnia or anxiety?

The start of the problem

Part of the trigger for the abusive use of zolpidem, according to part of the national medical community, was flexibility in access. Until the end of the 1990s, the drug was on the Ministry of Health’s list of “black stripe medicines”. To be able to purchase it, patients had to present a blue prescription at the pharmacy, which is more difficult to obtain.

In December 2001, however, the National Health Surveillance Agency (Anvisa) removed the medicine from the “black stripe” group and established that individuals could purchase the medicine with a special control prescription, one issued in two copies, one for patient and another for pharmacy. In practice, it is less rigorous.

Furthermore, the patent for zolpidem – which was released by the Food and Drug Administration (FDA), the body that approves medicines and treatments in the United States, in the early 1990s – expired in 2007. As a consequence, at least ten different companies Here in Brazil, they began to produce generics of the medicine, which generated an explosion in production and sales.

Anvisa informed the report that just over 13 million boxes of zolpidem were sold in 2018. In 2019 and 2020, 18 million boxes were sold each year. As of 2021, the annual number of sales has remained above 20 million. In the middle of that year, a survey by Consulta Remédios, a platform that allows you to compare prices, showed that zolpidem was the most sought after medicine during the new coronavirus pandemic.

For Dr. Ratzke, the entry of generics caused companies to invest heavily in advertising with doctors and users, which helped increase access. “Almost all laboratories that have generic zolpidem and similar products give discount cards so that people can buy a box and receive a 95% discount coupon on the second box, which costs less than five reais,” he reports.

Risks of abusive use of zolpidem

One of the possible side effects of controlled use of zolpidem is anterograde amnesia, a type of memory loss that occurs when a person cannot remember recent events. There are reports of people calling others, eating, shopping on their cell phones and even driving without realizing it. On TikTok, there are at least 4,354 posts about side effects with the hashtag zolpidem.

When used in doses higher than recommended, however, symptoms are more severe, according to Dr. Alexandre Pinto de Azevedo, psychiatrist at the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo (HC-FMUSP) and member of the Brazilian Sleep Association (ABS).

“The main physical risk is dependence on the substance. But there are other repercussions such as rebound insomnia, impaired attention and concentration, dizziness and risk of falls, impairment of professional and academic skills. Furthermore, when a situation of dependence is established, inappropriate behavior may also occur to obtain the medication, which is officially sold with a prescription retention.”

One study published in 2014 in the “Journal of Addictive Diseases” reported that, between 2003 and 2010, in France, there was an increase in “suspicious prescriptions that possibly indicate abuse”, and zolpidem was the medicine most associated with prescription falsification.

See also: Can Zolpidem cause blackouts? What you need to know before taking the medicine

Addiction treatment

Dependent behavior can set in when the patient experiences physical and psychological symptoms when trying to stop using it without medical supervision. Azevedo says that it is important to highlight, however, that the medicine remains indicated for the treatment of insomnia in all treatment guidelines (national and international), as long as the appropriate guidelines are followed.

Depending on the amount used daily, the appropriate way to deal with zolpidem dependence is through inpatient detoxification, according to Dr. Ratzke. This is because abrupt discontinuation can trigger withdrawal symptoms, such as tremors, sweating, nausea, feelings of anxiety and palpitations, as well as seizures. At the hospital where he works, three patients presented convulsive episodes, as reported in study.

“The risk is very high that you will take it on an outpatient basis and the person will have a seizure. So a patient, for example, who uses these 1,700 milligrams per day, there is no way you can treat him outside the hospital, you know? It would have to be either in a psychiatric hospital, or in a clinical hospital with support. Hospitalization for detox generally lasts 28 and 30 days for chemical dependencies”, explains the doctor.

During treatment, according to the specialist, zolpidem is initially replaced by diazepam, a benzodiazepine with a long half-life (that is, it stays in the body longer) and is easier to withdraw later. The period to begin overcoming addiction, however, is three months, according to the National Institute on Drug Abuse (Nida) in the United States.

Who is most affected?

A most cases of addiction described of zolpidem involves female people, typically aged between 35 and 50 years, with associated psychiatric comorbidities, such as anxiety It is depression. The fact that women suffer more from insomnia may be related to their prevalence among those who abuse the medication. According to ABS, insomnia affects 73 million people.

One study from the National Sleep Foundation of the United States in 2023 points out that female people have more sleep disorders than men due to hormones. Overload generated by excessive work, domestic activities and family care may also be associated with the problem, according to another study last year published by the Federal University of Santa Catarina (UFSC) in partnership with the Oswaldo Cruz Foundation (Fiocruz), focused on elderly women.

The Doctor. Ratzke says another group affected by misuse is healthcare professionals. As the medicine was sold as something that did not cause problems, doctors not only started prescribing it a lot, but also taking it. “What we see is a lot of dependence on zolpidem from doctors, pharmacists and nurses, because they end up having relatively easy access and the medicine has the illusion that it is not addictive.”

How to deal with the problem?

Preventing abuse begins with responsible medical prescription, according to Dr. Azevedo. “By carrying out a sufficient medical interview to evaluate the individual characteristics of each patient, in addition to an accurate diagnosis of the insomnia subtype, the medication indication is adapted to the clinical presentation of insomnia and the risk of dependence or abuse can be greatly reduced. ”

He also says that zolpidem should usually be avoided in patients undergoing psychiatric treatment that has not yet been stabilized, such as those with mood and anxiety disorders, people with personality disorders and those with a history of abusive use or dependence on illegal or illicit substances. “These individuals are more vulnerable to using a higher dose of medication than proposed because they are more emotionally vulnerable, due to other characteristics of impulsivity or even due to the tendency to abuse behavior.”

The Doctor. Ratzke says that, from a regulatory point of view, the ideal would be for Anvisa to put the medicine back on the black list. Furthermore, he says, laboratories that produce generics should end the distribution of “almost free samples” of the medicine. “Because the fact that the person has to pay the money to buy is already a limitation. If she gets it for free, it already greatly encourages abuse.”

Asked about the category of the drug and the increase in cases of dependence, Anvisa said that zolpidem is already in a control group that aims to provide a strict link between access “to the substance and its therapeutic need, under the prescription and guidance of the medical professional.”

The regulatory agency also says that, as the competent body for improving control measures, “it maintains in its continuous work process the review of applicable actions so that this correlation (access-need) remains”. Furthermore, it states that it is “attentive to any safety signs that require measures to minimize risks for the Brazilian population”.

See also: Zolpidem: how to use it correctly?

About the author: Lucas Gabriel Marins is a journalist and future biologist. He is interested in subjects related to science, health and economics.