Dangerous Mix: The Risks of Alcohol Use with Zolpidem

The concurrent use of alcohol and Z drugs, such as zolpidem, presents significant health risks, especially concerning effects on the central nervous system and an increase in risky behaviors.

The so-called Z drugs are a class of medications widely used for the short-term treatment of insomnia and other sleep disorders (1). This term encompasses drugs like zolpidem, zopiclone, and eszopiclone, which were developed as alternatives to benzodiazepines, offering a sedative-hypnotic effect with lower risks of dependence and side effects. They are called Z drugs because of the initial letter of their main names, making it easier to refer to the class of non-benzodiazepine hypnotics aimed at sleep.

The mechanism of action of Z drugs involves the selective stimulation of GABA-A receptors in the brain, promoting a calming and hypnotic effect. This occurs through the amplification of GABA neurotransmitter activity, which inhibits neuronal excitability and induces sleep (2). Although effective, these substances carry risks, especially when combined with others that depress the central nervous system, such as alcohol.

The concurrent use of alcohol and Z medications, like zolpidem, presents significant health risks. According to the FDA, the combined use can result in excessive sedation, coordination difficulties, and in extreme cases, complex behaviors during sleep, such as walking, driving, or performing other activities while unconscious. Additionally, there is an elevated risk of respiratory depression and other serious effects, as alcohol enhances the sedative effects of Z drugs (3).

Activities requiring full attention, such as driving, should be avoided after using these medications, and combined use with alcohol should be avoided to reduce the risks of severe adverse effects, such as sleepwalking and amnesia. People with a history of substance abuse should be evaluated with caution before prescribing these drugs (3). To minimize risks, ANVISA (Brazilian Health Regulatory Agency) has recently changed the prescription requirements for zolpidem and other Z drugs, making it stricter due to the risk of dependence and abuse associated with these substances (4). Thus, it is essential that the use of these medications be strictly controlled, with restrictions on their short-term use, continuous medical supervision, and guidance on the risks of concurrent alcohol use.

References:

1. FDA Label for Ambien®. Drugs@FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019908s027lbl.pdf
2. Neumann, E., Rudolph, U., Knutson, D. E., Li, G., Cook, J. M., Hentschke, H., Antkowiak, B., & Drexler, B. (2019). Zolpidem Activation of Alpha 1-Containing GABAA Receptors Selectively Inhibits High Frequency Action Potential Firing of Cortical Neurons. Frontiers in pharmacology, 9, 1523. https://doi.org/10.3389/fphar.2018.01523
3. Taking Z-drugs for Insomnia? Know the Risks. U.S. Food and Drug Administration. September 9, 2020. https://www.fda.gov/consumers/consumer-updates/taking-z-drugs-insomnia-know-risks
4. Agência Nacional de Vigilância Sanitária. (2024, 17 de abril). Medicamento zolpidem terá alteração no tipo de receita para prescrição e venda.