Between 1996 and 2013, the number of adults who filled a benzodiazepine prescription rose by 67%, increasing from 8.1 million to 13.5 million. During the same period, the quantity of benzodiazepines dispensed more than tripled, going from 1.1 kg to 3.6 kg per 100,000 adults. According to the National Institute on Drug Abuse, benzodiazepine overdose deaths surged to over 8,791 in 2015, up from 1,135 in 1999—an increase roughly 40 times greater than the growth of the U.S. population during that time.
Key Facts About Benzodiazepines
Despite these figures, the opioid epidemic has received more attention—and with good reason. Over three-quarters of benzodiazepine-related deaths involved concurrent opioid use. However, the rapid growth of benzodiazepine prescriptions and the subsequent rise in overdose deaths are equally alarming. From 1991 to 2009, Medicaid spending on benzodiazepines surged by nearly $40 million, and the rate of co-prescribing opioids and benzodiazepines nearly doubled between 2001 and 2013.
In 2016, the FDA issued a black-box warning—the most severe warning label the Food and Drug Administration uses—to highlight the dangers of co-prescribing benzodiazepines and opioids.
What Are Benzodiazepines?
Benzodiazepines, commonly known as benzos, belong to a class of sedative drugs. Classified as Schedule II-IV substances by the DEA, benzos produce calming and sedative effects similar to opioids, though they carry a significantly lower risk of overdose when taken alone. However, when combined with opioids, their lethality increases dramatically. Unlike opioids, which target opioid receptors and can cause respiratory failure, benzos target GABA receptor molecules, which primarily affect cognitive functions rather than vital life processes. As a result, benzos may lead to mental drowsiness, amnesia, and impaired learning and motor control rather than lung failure.
Benzos induce feelings of calmness and relaxation. At higher doses, they can cause vertigo, drowsiness, and muscle incoordination. The effects of benzos can last from a couple of hours to more than a day, depending on dosage and tolerance. Unlike other sedatives and opioids that can suppress the nervous system to the point of respiratory failure, benzos do not carry this risk. While these drugs are prescribed to alleviate anxiety, nervousness, restlessness, and insomnia, misuse can lead to the very symptoms they are meant to treat.
Common Benzodiazepines
History of Benzodiazepines
Benzodiazepines were first developed in the 1950s in New Jersey by chemists working for the Swiss pharmaceutical company Hoffman-La Roche. The first benzodiazepine, chlordiazepoxide—better known as Librium—was discovered accidentally in 1957 when researchers noticed a “beautiful crystalline” structure during tests for new tranquilizers. Upon further testing, they found that the compound was remarkably effective as a sedative and muscle relaxant. Librium was introduced to the market in 1960, followed by diazepam, commonly known as Valium, in 1963.
Before benzodiazepines, barbiturates were the most commonly prescribed sedatives. Developed by German pharmaceutical companies in the early 20th century, barbiturates became popular over-the-counter medications during the Great Depression in the United States. Although marketed as safer alternatives to opiates, these claims were largely promotional. By the time the U.S. entered World War II in 1941, Americans were consuming over a billion barbiturates annually. In 1951, Congress mandated that barbiturates be prescribed by doctors, significantly reducing their use and creating an opportunity for the development of the next generation of sedatives—benzodiazepines.
By 1983, 17 different benzodiazepines were available globally, with a market value exceeding $3 billion. By the 1970s, benzodiazepines had become the most prescribed drug in the world. It was estimated that one in five women and one in ten men in Europe had been prescribed the medication at some point. However, concerns about the potential for abuse began to emerge. Women were more frequently prescribed benzodiazepines than men, often for issues like insomnia and irritability, and advertising campaigns exploited gender stereotypes to capitalize on this trend.
As the 1980s approached, both patients and doctors became increasingly vocal about the risks of developing a dependency on benzodiazepines. More benzodiazepines were introduced to the market, and in 1979, Senator Ted Kennedy led a Senate hearing to address the dangers of these drugs. However, the hearings eventually stalled as different manufacturers deflected blame onto older versions of the drug, arguing over the safety of various formulations like Klonopin, Xanax, and Valium based on molecular differences. Despite growing concerns, benzodiazepine prescriptions began to decline globally, except in the United States, where the number of prescriptions continued to rise.
In 1992, a major class action lawsuit was filed in the UK, involving 14,000 patients represented by 1,800 law firms. The lawsuit, which was the largest of its kind in the UK at the time, alleged that benzodiazepine manufacturers had failed to adequately warn patients and doctors about the risks of dependence and other health hazards associated with the drugs. As a result of the lawsuits and increasing public awareness, benzodiazepine prescriptions in the UK dropped from 32 million annually to about 18 million. In contrast, prescription rates in the United States continued to rise, especially with the introduction of similar drugs known as Z-drugs, including zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta) in the 2000s.
In the U.S., the percentage of adults filling benzodiazepine prescriptions increased from 4.1% to 5.6% between 1996 and 2013, with the overdose rate rising from 0.58% to 3.07% during the same period, plateauing after 2010.
Benzodiazepines Targeted at Women
As previously mentioned, benzodiazepines were frequently prescribed during the mid-20th century to treat what advertisers at the time referred to as “womanly problems.” The sexist tone of these advertisements was typical of the era, but even today, clinicians appear more likely to prescribe benzodiazepines to women. In 2013, over 61 million benzodiazepine prescriptions were written for women, compared to 29 million for men.
According to the Anxiety and Depression Association of America, women are more likely than men to be diagnosed with an anxiety disorder. This disparity may be due to various factors, including differences in brain chemistry, entrenched societal stereotypes, the higher likelihood of women experiencing physical and mental abuse, and the fact that women are more likely to seek medical help for mental health issues than men.
Benzodiazepine Withdrawal
Like other drugs, benzodiazepine abuse often leads to physical dependence, where the body struggles to function without the substance. Withdrawal from benzodiazepines is associated with severe risks, including seizures and potential death, along with various other symptoms that could trigger relapse if not managed carefully. Similar to alcohol and barbiturates, benzodiazepines affect GABA receptors, significantly increasing the risk of seizures during withdrawal. Symptoms of withdrawal include:
Depending on the severity of the addiction, withdrawal can last from a few days to a full week, with acute symptoms like depression, cognitive fog, and insomnia potentially lingering for months. In severe cases, more serious symptoms such as seizures and psychosis may occur, though these are less common. During the initial stages of withdrawal, the brain’s reserves of endorphins and dopamine are significantly depleted, which contributes to the prolonged duration of withdrawal as these chemicals take time to naturally replenish and return to normal levels.
Harm Reduction Through PDMP (Prescription Drug Monitoring Program)
The Prescription Drug Monitoring Program (PDMP) is a tool used by states to combat prescription drug diversion and abuse. Although each state’s program varies, the core concept involves maintaining a database that tracks prescriptions to identify potential issues such as doctor shopping, overprescribing, and dangerous co-prescriptions. When physicians are required to consult the PDMP before prescribing medications, it can help mitigate the risk of abuse and problematic co-prescriptions.
Studies indicate that states with PDMPs have seen an 8 percent reduction in opioid prescription rates and a 12 percent decrease in opioid overdose deaths. Data from the CDC shows that opioid prescriptions increased by 10 percent from 2006 to 2010, but decreased by more than 13 percent from 2012 to 2015. Research also indicates that patients are at higher risk for abuse if they use opioids daily for more than five days, and they are less likely to discontinue use after more than 90 days.
Currently, 29 states utilize PDMP strategies to mitigate prescription drug abuse. Over the past decade, the implementation of these programs has likely contributed to a decrease in opioid prescriptions from 782 morphine milligram equivalents (MME) per capita in 2010 to 640 MME per capita. While this demonstrates progress, the number of opioid prescriptions remains significantly higher compared to 1999. Notably, the U.S. opioid prescription rate is nearly four times higher than that of Europe.
Opioid prescription rates vary widely across the United States, with the highest prescribing areas issuing opioids at nearly six times the rate of other regions. Factors associated with higher prescription rates include a larger percentage of non-Hispanic whites, higher prevalence of diabetes and arthritis, elevated unemployment rates, and increased Medicaid enrollment.
In Conclusion
Drug and alcohol addictions are among the most devastating challenges facing the world today. Benzodiazepines, in particular, pose significant dangers and contribute to these severe addictions. The journey toward healing—whether for individuals, families, communities, or globally—begins with acknowledging the risks associated with these substances. At Sunrise Recovery, we are committed to providing a supportive network and resources to help you overcome addiction. Explore our website to discover more about our inpatient rehab centers in Indiana and how we can assist you on your path to recovery.
