So-called “z drugs”: commonly used hypnotics and clinical risk

The so-called Z drugs—zolpidem, zopiclone, and zaleplon—are non-benzodiazepine hypnotics commonly prescribed for the treatment of insomnia. They act as selective GABA-A receptor agonists, facilitating sleep onset and maintenance.

They differ from classic benzodiazepines in their chemical structure but share a similar pharmacological profile, which is why they have been widely adopted in clinical practice, particularly in patients with affective disorders.

Insomnia and depression: a common and persistent symptom

In patients with major depressive disorder, insomnia is one of the most common symptoms, and its persistence can predict relapses, prolong the duration of the episode, and decrease the effectiveness of treatments.

For this reason, clinicians often resort to Z drugs as an adjunctive symptomatic treatment. Although they may bring about temporary improvement in sleep patterns, their use should be carefully evaluated, considering the short-term benefits against the potential long-term risks.

Clinical risks associated with prolonged use

Although initially promoted as “safer” alternatives to benzodiazepines, Z drugs have been shown in clinical and population studies to also cause tolerance, dependence, and withdrawal syndrome.

In addition, adverse effects such as cognitive impairment, complex behaviors during sleep (e.g., sleepwalking or unconscious nighttime eating), daytime sleepiness, falls in older adults, and disruption of sleep architecture have been reported. All of these can worsen the underlying depression, especially if not accompanied by other therapeutic interventions.

The problem of self-medication

A worrying phenomenon is the increase in self-medication with Z drugs. Some patients access these drugs without medical supervision, mistakenly believing that they are harmless.

This unregulated use can aggravate depressive symptoms, make insomnia chronic, and increase the risk of dependence. Clinical practice