In William Shakespeare's "Hamlet," the tragic character states, "To die, to sleep. To sleep, perchance to dream — ay, there's the rub, For in that sleep of death what dreams may come."

However, the sleep of death is what close to 15 million adults risked as they filled their sleep, sedative, anxiolytic or anticonvulsant prescriptions containing benzodiazepine. A new study published in the April issue of the American Public Health Association Journal reported an increase in overdose mortality related to benzodiazepine prescriptions between the years 1996 and 2013.

Marcus A. Bachhuber, M.D., of the Montefiore Medical Center/Albert Einstein College of Medicine, led the team undertaking the study. They found the overdose death rate went from .58 deaths per 100,000 adults in 1996 to a rate of 3.14 deaths per 100,000 in 2010. While the rate did not increase after 2010, it also did not show any decline. However, the rate of use for these prescriptions did increase by 67 percent, with 8.1 adult users in 1996 and 13.5 million in 2013.

The Centers for Disease Control and Prevention reported in 2012 that clinicians wrote benzodiazepine prescriptions at the rate of 37.6 scripts per every 100 adults. The CDC also reported a regional difference in this rate, with West Virginia having the highest rate at 71.9 per 100 adults, followed by Alabama at 61.9 and Tennessee at 61.4. The states with the lowest rate were Hawaii 19.3, Alaska 24.0 and Wyoming at 24.9. (South) The reasons for greater us of benzodiazepine use in the South is poorly understood.

Being a veteran and receiving prescriptions for both opioid analgesics and benzodiazepines are risk factors for overdose death — either accidentally or intentionally. Between the years 2004 and 2009, 112,069 veterans received opioid analgesics and, of these, 27 percent also received benzodiazepines.

Tae Woo Park, Ph.D., of The Warren Alpert Medical School of Brown University, along with his colleagues, undertook an analysis of the reported data. They found half the deaths from a drug overdose occurred when both types of drugs were used. They also found the risk of death from a drug overdose increased with an increase in the daily dose of benzodiazepine.

The group concluded that veterans having received prescriptions for opioid analgesics were at a greater risk of death from drug overdoses if they also received a prescription of benzodiazepines, and the increased risk was dose-related.

The reports of benzodiazepines having an impact on the development of cognitive dysfunction are mixed, with some reports of an increased risk of dementia and others being less conclusive. The reports of benzodiazepines placing users at greater risk of injury in motor vehicle accidents is definitely conclusive.

The sleep of death is not what is intended when a clinician prescribes benzodiazepines. However, the frequency of death with the use of these drugs is alarming.

Researchers such as Bachhuber suggest interventions are necessary to reduce the use of benzodiazepines, and there is an additional need to develop mechanisms to improve their safety when they are used.