Benzodiazepine overdose is a common cause of hospitalization in the United States, associated with about 30% of overdose cases. Such incidences fixedly increase in quantity and are important to consider when dealing with patients who have a history of drug abuse or predisposing factors for a possible overdose. These comprise e.g. psychological disorders, post-traumatic stress syndrome in patients with a military background, depressive or suicidal states.

Benzodiazepines are a class of medication with anxiolytic, analgesic, sedative and hypnotic features marking them a target of drug abuse and subsequent overdose [1]. Illegitimate practices and 'doctor shopping', involving patients visiting multiple doctors, lead to the unreasonable prescription of benzodiazepines and consecutive abuse [2]. Psychiatric patients, on the other hand, are known to use benzodiazepines in an attempt of suicide or intentional self-harm [3].

Often, polydrug users execute the administration of benzodiazepines in combination with alcohol, antidepressants or opioids giving rise to the failure of cardiovascular and respiratory systems [4]. Other complications include neurological, renal impairment, muscular complications like hypotonia, and possible hearing loss.

Acute manifestations in overdosed patients usually involve collapse with seizures, cyanosis due to respiratory failure, loss of consciousness, coma and possible cardiac arrest [5]. On examination of the eyes, the patient might have fixed miosis or pinpoint pupil.

Benzodiazepine overdose is managed according to possible complications.

A magnetic resonance imaging (MRI) of the brain is a necessity if the patient appears unconscious, comatose and with a possible risk of acidosis. The MRI will expose herniations, edema and diffuse white matter injury (leukoencephalopathy) relatively excluding the lesions of the gray matter. The white matter injury may also be of connection with the use of chemotherapy agents and exposure to toxins e.g. carbon monoxide. Signs of edema and herniation may evolve and be the cause of death if not handled or monitored appropriately [6] [7].

A computed tomography (CT) examination findings include hypodensity in the affected area of the white brain matter, correlating to the clinical picture found in MRI. Reports suggest that early in the disease, the imaging of the patient's brain can appear normal which leads to discharge from the hospital. After about two weeks, a rapid deterioration of the white matter precedes and involves serious changes in consciousness, behavior, gait, parasympathetic system, etc., advancing to dramatic complications like coma or quadriparesis. Thus the importance of monitoring the affected patient is suggested [8].

Urine sample analysis may expose high levels of benzodiazepines [6].

Lumbar puncture with a collection of the cerebrospinal fluid is useful to exclude other diagnoses e.g. herpes simplex virus infection, Epstein-Barr virus disease or other infections associated with brain tissues that cause similar radiologic findings. The analysis includes cell count, protein, and glucose level determination [9].

Electroencephalography (EEG) is optional and used to discover electrical potential abnormalities if the patient experienced neurologic signs e.g. seizures. The EEG might reveal slowing of background in low frequencies [6].

Treatment for benzodiazepine overdose focuses on stabilizing the patient and preventing further complications. In mild cases, monitoring and supportive care may be sufficient. In more severe cases, medical interventions such as intravenous fluids, oxygen therapy, and medications like flumazenil, a benzodiazepine antagonist, may be administered. Flumazenil can reverse the effects of benzodiazepines but is used cautiously due to potential side effects.

The prognosis for benzodiazepine overdose is generally favorable, especially with prompt medical intervention. Most patients recover fully without long-term effects. However, the outcome can be more serious if the overdose involves multiple substances or if there is a delay in treatment. Chronic misuse of benzodiazepines can lead to dependence and withdrawal symptoms, which require specialized care.

Benzodiazepine overdose can occur accidentally or intentionally. Accidental overdoses often happen when individuals take more than the prescribed dose, either due to misunderstanding instructions or seeking enhanced therapeutic effects. Intentional overdoses may be associated with substance abuse or suicide attempts. The risk of overdose increases when benzodiazepines are combined with other central nervous system depressants, such as alcohol or opioids.

Benzodiazepine overdoses are a significant public health concern, particularly in countries with high prescription rates. They are more common in adults, especially those with a history of substance abuse or mental health disorders. The incidence of benzodiazepine overdose has been rising, partly due to increased prescribing and the concurrent use of other sedative substances.

Benzodiazepines enhance the effect of a neurotransmitter called gamma-aminobutyric acid (GABA) in the brain, which has a calming effect on the nervous system. In overdose situations, excessive GABA activity can lead to profound sedation, respiratory depression, and impaired motor function. The risk of severe respiratory depression is heightened when benzodiazepines are combined with other depressants.

Preventing benzodiazepine overdose involves careful prescribing practices, patient education, and monitoring. Healthcare providers should prescribe the lowest effective dose for the shortest duration necessary and educate patients about the risks of overdose and the dangers of mixing benzodiazepines with other substances. Patients should be encouraged to follow their prescription instructions closely and to store medications safely to prevent accidental ingestion by others.

Benzodiazepine overdose is a potentially life-threatening condition resulting from the excessive intake of benzodiazepines. It presents with symptoms ranging from drowsiness to severe respiratory depression. Prompt diagnosis and treatment are crucial for a favorable outcome. Prevention strategies focus on responsible prescribing and patient education to minimize the risk of overdose.

If you or someone you know is taking benzodiazepines, it's important to understand the risks associated with these medications. Always follow your doctor's instructions and never take more than the prescribed dose. Be aware of the symptoms of overdose, such as extreme drowsiness, confusion, and difficulty breathing. Avoid mixing benzodiazepines with alcohol or other drugs, as this can increase the risk of serious side effects. If you suspect an overdose, seek medical attention immediately.

1. Bachhuber MA, Hennessy S, Cunningham CO, Starrels JL. Increasing Benzodiazepine Prescriptions and Overdose Mortality in the United States, 1996–2013. Am J Public Health. 2016;106(4):686-688.
2. Peirce GL, Smith MJ, Abate MA, Halverson J. Doctor and pharmacy shopping for controlled substances. Med Care. 2012;50:494–500.
3. Shin HI, Lin MC, Lin CC, et al. Benzodiazepine therapy in psychiatric outpatients is associated with deliberate self-poisoning events at emergency departments—a population-based nested case-control study. Psychopharmacology (Berl). 2013;229:665–71.
4. Slavova S, Bunn TL, Talbert J. Drug Overdose Surveillance Using Hospital Discharge Data. Public Health Rep. 2014;129(5):437-445.
5. Martins SS, Sampson L, Cerdá M, Galea S. Worldwide Prevalence and Trends in Unintentional Drug Overdose: A Systematic Review of the Literature. Am J Public Health. 2015;105(11):e29-e49.
6. Aljarallah S, Al-Hussain F. Acute fatal posthypoxic leukoencephalopathy following benzodiazepine overdose: a case report and review of the literature. BMC Neurol. 2015;15:69.
7. Kim JH, Chang KH, Song IC, et al. Delayed encephalopathy of acute carbon monoxide intoxication: diffusivity of cerebral white matter lesions. AJNR Am J Neuroradiol. 2003;24(8):1592–7.
8. Chang WL, Chang YK, Hsu SY, Lin GJ, Chen SC. Reversible delayed leukoencephalopathy after heroin intoxication with hypoxia: a case report. Acta Neurologica Taiwanica. 2009;18(3):198–202.
9. Wallace IR, Dynan C, Esmonde T. One confused patient, many confused physicians: a case of delayed post-hypoxic leucoencephalopathy. QJM Monthly J Assoc Physicians. 2010;103(3):193–4.