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Mixing drugs: what are the trends and risks?

Mixing drugs such as sleeping pills and opioid pain medicines is a dangerous practice. A recent study analyzed the prevalence, trends, and risk factors of mixing drugs in the United States.

Older and chronically ill patients are the most at risk for inappropriately mixing drugs. One of the consequences of mixing drugs is possible drug interactions and side effects. Two drugs that are commonly taken together are benzodiazepines and opioids. Although there are no drug interactions between opioids and benzodiazepines, the side effects of both drugs are very similar. Both benzodiazepines and opioids cause central nervous system depression. This can cause slowed or difficult breathing and sedation. Taking both of these drugs at the same time can cause additive side effects, which can be dangerous and lethal.

Mixing benzodiazepines and opioids increase mortality and morbidity risks

As a safety precaution, the US Food and Drug Administration (FDA) issued a warning about the use of benzodiazepines and opioids. The FDA went as far as publishing this warning on all benzodiazepine and opioid drug packaging. The increased mortality and morbidity associated with mixing benzodiazepines and opioids are well-established. Mixing opioids and benzodiazepines is associated with a greater than two-fold risk of emergency room visits and hospital admissions.

The danger of mixing different types of benzodiazepines

A second form of inappropriately mixing drugs is the use of two different types of benzodiazepines. There are two groups of benzodiazepine medications, nonselective and selective benzodiazepine receptor modulators.

Selective benzodiazepine receptor modulators bind more specifically to the GABA receptors found in the brain which is associated with the sedative effect. Nonselective benzodiazepine receptor modulators bind to many GABA receptors in the body. The confusion extends in the name of the drugs. Nonselective benzodiazepines usually end in “lam” or “pam” such as alprazolam and lorazepam. Selective benzodiazepines usually start with the letter “z” such as zopiclone and zolpidem. These differences in benzodiazepines can mislead physicians into believing that selective benzodiazepines are not benzodiazepines.

Researchers from the St. Michael’s Hospital in Toronto, Canada explored the prevalence, trends, and risk factors of mixing selective and nonselective benzodiazepines and benzodiazepines with opioids in the general US population. The results of this analysis were published in Sleep.

Population-level data from the US covering 16 years were analyzed in this study. The researchers used the National Health and Nutrition Examination Surveys  (NHANES). The NHANES is a national survey that is launched by the Centers for Disease Control and represents the civilian US population. Data are collected every two years, and this study included data from eight cycles from the 1999-2000 cycle to the 2013-2014 cycle. The Canadian researchers collected information on prescription drug use, sociodemographic data, and other health data.

Trends of mixing opioids and benzodiazepines have risen up to the millions

The results of this study conclude that the use of two different benzodiazepines and the use of benzodiazepines and opioids has progressively risen in the US from 1999 to 2014. The prevalence of mixing opioids and benzodiazepines increased from 0.39% in 1999-2000 to 1.36% in 2013-2014.  The prevalence of mixing nonselective and selective benzodiazepines in 1999-2000 was 0.05% and rose to 0.47% in the 2013-2014 cycle. Although these percentages seem very minor, they represent millions of US citizens.

Sociodemographic data were collected in this study to evaluate trends and risk factors associated with mixing drugs. It is known that women are more likely to receive benzodiazepines and opioids, but in this study, patient gender was not associated with an increased risk of mixing drugs.

Older adults are more likely to use benzodiazepines and opioids

Older adults are more likely to use benzodiazepines and opioids.  In this analysis, older age was less likely associated with mixing drugs. Caucasians were not more likely to use different benzodiazepines compared with African- and Mexican-Americas. However,  Caucasians were more likely to use different benzodiazepines compared with “other ethnicities” such as non-African Americans and non-Hispanic patients. Surprisingly, behaviours such as cigarette smoking and problem drinking were not associated with increased risk of mixing benzodiazepines. Current smokers were, nevertheless, associated with increased risk of combining opioids and benzodiazepines.

Psychiatric diseases and morbid obesity were associated with mixing drugs

Health data was also collected. It was shown that psychiatric diseases were associated with mixing drugs since pain, insomnia, and anxiety are frequently associated with psychiatric diseases.  Arthritis was also associated with mixing drugs because patients usually have chronic pain, insomnia, and anxiety. Surprisingly, morbid obesity was associated with combining both types of benzodiazepines. Benzodiazepine use leads to decreased physical activity which can cause obesity. Obesity is also associated with muscle and bone pain which leads to insomnia and increases benzodiazepine use.  This use is very concerning because obesity is associated with obstructive sleep apnea and benzodiazepines can worsen this condition.

Strong health data supported the findings of this study 

The almost two decades of prescription use, sociodemographic data, and health data from this large national survey is a major strength of this study. The researchers objectively confirmed patient drug use through the NHANES and did not rely on patient self-reporting.

An important limitation of the study was that drug use was only evaluated within the 30 days before the survey, so data from the rest of the year was missing. Data on how patients used psychoactive drugs was not evaluated. Patients could have been prescribed a drug and not actually taken it, or patients may not have necessarily used each drug every day. The findings of this study are exploratory in nature, and further studies are required to confirm the results.

More research needed to determine the cause of increased incidence of mixing drugs

In conclusion, this study has confirmed that mixing drugs, such as benzodiazepines and opioids has increased in the last two decades. Further research is required to determine the cause of this increase in inappropriately mixing drugs. Trends and risk factors associated with mixing psychoactive drugs were also analyzed in this study.

Certain patient populations are more at risk of mixing drugs. Combining nonselective and selective benzodiazepines and mixing benzodiazepines with opioids puts patients at risk of severe side effects. Effective strategies to minimize the risks of mixing drugs are necessary to put a stop to this risky practice.

Written by Jessica Caporuscio, PharmD


  1. Vozoris NT. Benzodiazepine and Opioid Co-Usage in the United States Population, 1999-2014: An Exploratory Analysis. Sleep. 2019.
  2. Wolters Kluwer Clinical Drug Information, Inc. (Lexi-Drugs). Wolters Kluwer Clinical Drug Information, Inc.; January 30, 2019.
Jessica Caporuscio PharmD
Jessica Caporuscio PharmD
Jessica received her Doctorate of Pharmacy from the University of Montreal in July 2014 and she has been working as a community pharmacist in the Greater Toronto Area since March 2015. She has a passion to communicate medical and drug information to her patients and other healthcare professionals. Jessica is also a marathoner and an Ironman triathlete. In her spare time, she is in her kitchen creating healthy recipes for her family.


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