Sedative/hypnotic withdrawal

Background

Sedative/hypnotics, including benzodiazepines, barbiturates, and non-benzodiazepine "Z-drugs" (e.g., zolpidem, eszopiclone), are commonly prescribed for anxiety, insomnia, and seizure disorders. While effective in the short term, these agents carry a significant risk for tolerance, physical dependence, and withdrawal upon abrupt discontinuation. The underlying pathophysiology of withdrawal stems from chronic modulation of gamma-aminobutyric acid (GABA) receptors, resulting in a state of central nervous system hyperexcitability when the inhibitory effect is suddenly removed [2]. Sedative/hypnotic withdrawal remains underrecognized in clinical practice despite its potentially life-threatening complications, such as seizures and delirium [5].

Clinical Features

For short-acting agents like alprazolam or zolpidem, withdrawal can begin within 6–24 hours after the last dose. Long-acting agents like diazepam may produce symptoms after several days.

Common features include:

Mild: anxiety, insomnia, restlessness, tremors, diaphoresis

Moderate: palpitations, nausea, myoclonus, perceptual disturbances

Severe: hallucinations, psychosis, seizures, and delirium tremens-like presentations

Symptoms typically peak within 48–72 hours but can persist for weeks, especially with long-term use [2]. A clinical feature distinguishing sedative/hypnotic withdrawal from alcohol withdrawal is the potential for prolonged symptoms due to the long half-life of some agents.

Differential Diagnosis