Benzodiazepines and “Z-Drugs” Increase Death Risk When Taken With Opioids

Opioid Prescription Pill Overdose

The risk of death increases when benzodiazepines or “z-drugs” are taken with opioids.

A new study by Vanderbilt University Medical Center researchers of more the 400,000 Medicare patients taking medications for insomnia found that the risk of death is increased when either benzodiazepines or “z-drugs” are taken with opioids.

The study, published on July 15, 2021, in PLOS Medicine and led by Wayne Ray, PhD, professor of Health Policy at VUMC, compared patients taking these drugs with opioids to comparable patients taking trazodone, another commonly prescribed sleep medication for older patients. The researchers found that those using benzodiazepines had a 221% increase in the risk of death from any cause and those taking non-benzodiazepine hypnotics, or “z-drugs,” had a 68% increased risk.

“Our findings indicate that the risks of benzodiazepine-opioid use go well beyond the recognized hazards of overdose. They also suggest that the z-drugs, thought to have better safety than the benzodiazepines, in fact are dangerous when prescribed in combination with opioid pain medications,” Ray said.

Benzodiazepines, including brand names such as Restoril, Ativan, and Halcion and the “z-drugs,” a type of medication known more commonly under names like Ambien, Lunesta, and Sonata, are among the most frequently prescribed medications for older adults.

Trazodone, a medication initially introduced for depression, is often prescribed in low doses for insomnia. Although researchers have speculated about the relative safety of these sleep medications, there is limited relative safety data.

Ray said the study findings could help to fill this data gap and thus lead to changes in both provider behavior and policy.

“Our findings add urgency to efforts to limit concurrent prescribing of benzodiazepines and opioids. They also suggest that targeted warnings are needed to advise older patients and their providers regarding the potential risks of taking z-drugs with opioids,” Ray said.

Reference: “Mortality and concurrent use of opioids and hypnotics in older patients: A retrospective cohort study” by Wayne A. Ray, Cecilia P. Chung, Katherine T. Murray, Beth A. Malow, James R. Daugherty and C. Michael Stein, 15 July 2021, PLOS Medicine.
DOI: 10.1371/journal.pmed.1003709

The study was supported by a grant from the National Heart, Lung and Blood Institute.

7 Comments on "Benzodiazepines and “Z-Drugs” Increase Death Risk When Taken With Opioids"

  1. William Martin Readling | July 16, 2021 at 12:09 pm | Reply

    Not surprising. Both classes of drugs reduce respiration, and depress central nervous system activity.

  2. As one who took a 50mg Tramadol daily for Arthritis, bulging disc pain and sciatica, then a 2mg Ativan each evening, and then an Ambien 10mg at bedtime,(for 10 yrs orlonger)and had pain and Anxiety relief and excellent sleep, I would testify that there was no risk of overdose, but greatly increased quality of life, until I moved and a frightened MD decided I had to be removed from this med routine, and make me suffer, as these meds were prescribed for conditions that have continued untreated, because of the drug abuses of others who overdosed using non prescribed drugs or some tainted with Fentanyl. The many who took prescribed Benzos,pain meds and sleeping meds without any abuse, addiction, or respiratory depression, should be included in any reporting of how dangerous it is. We are overlooked, and there were many of us, now deprived of previously available treatment.

  3. Jeannette Price | July 18, 2021 at 11:34 am | Reply

    I have taken them together for 15 years. Never have I come close to an overdose. I have been repeatedly abused by the medical community because of my medication. Why the fear and prejudice. Talk to people who have been on them. This is definitely a fake article. This piece definitely comes from a place of ignorance. Prop is pushing this crap and you feed it to the public. I use to have quality of life. Educate yourself.

  4. Because of misleading articles such as this, I have been denied treatment for chronic anxiety I have had all of my adult life. I visit pain mgmt every month for my opioids, but am allowed SIX .5 mg lorazepam per MONTH. That is NOT treating my anxiety. It is driving me to want alcohol, which will result in me losing my pain meds, which WILL LEAD TO MY SUICIDE.

  5. What utter and complete nonsense! I’ve taken both with a powerful muscle relaxant for 30 years! You people have no idea how severe anxiety effects every aspect of a person’s life just like you have no idea how medications work in tandem. There is risk involved in everything like crossing the street puts me at risk of being hit by a car. According to you people I should never cross the street to eleminate the risk of being hit by a car. How do you sleep at night knowing the suffering you inflict on people? Why don’t you ever ask the people like me who have had long term experience with these combinations of medication? You won’t because you have 0 interest in the FACTS! STOP INTERFEARING WITH MY MEDICAL CARE!

  6. I agree with these people I too suffer from chronic pain and take 50 mg of Tramadol twice daily with my Thyroid medication once a day. I have had three major shoulder surgeries all three surgeries had failed. May 2021, I had a Functional Capacity Evaluation done, I ended up with a torn Labrum which I had never had before. My surgeon told me it was due to age, I disagree, according to Mayo Clinic, stated 40% is due to age and 60% is due to injury. I never had a n torn Labrum until the FCE was completed. Now, I cannot have my Labrum repaired because I am not 30 something. I guarantee if it is a Physician, Celebrity or Professional Athlete or someone who is wealthy no questions would be asked, I am Middle Class, I am forgotten like most people. Medical personnel could care less if someone is suffering and medical care sucks. The people who overdose are the ones who mix different medications took opioids with other opioids and consumed alcohol. There are blood tests that Physicians can do along with urine tests to see if the patient is on other narcotics before an narcotic is prescribed. Slowly are rights are being taken away.

  7. I have been in Pain management for 26 years I’ve had 34 surgeries and just had my seventh back surgery in September I had severe stenosis work it hardly walk the pain was atrocious I have terrible sciatica and three of the seven back surgeries were fusions my normal blood pressure is 116/70 but my pain is so bad I’m on three blood pressure medication‘s because my blood pressure every day is at least 180/110 and it last for hours because I don’t have enough pain medication on board anymore the pain doctor has taken away most of my pain medication I was on OxyContin for 12 years 80 mg a day plus muscle relaxers and then for the past nine years I have been on fentanyl as much as 100 µg and now 25 µg right after my back surgery the pain doctor took away my muscle relaxers and I’m having spasms in my back like crazy because they had to re-open me up five days after my seventh back surgery because they had accidentally sutured one of the drain tubes down inside my back my Neurosurgeon is really frustrated that I can’t get pain relief that I deserve he said out of all of his surgeries and he’s done over 100 I was in his top three of the hardest one he ever had to do he ended up operating so long I lost 2 pints of blood he said my back was like a war zone and they had to give me 2 pints of blood and recovery. I see a psychiatrist for depression I work full-time because I have to I throw up every day because my pain is so severe I’m beginning to feel hopeless I’ve never think about suicide but I do pray And ask God to please bring me home. I have chest pains because I’ll go to her three days with no sleep because the sciatica is so severe but I still have to go to work. I have no quality of life I live on ice packs I have one at work and I have five at home and I lay on them constantly to know I’m some of the pain because it’s unbearable it’s patience like me or not getting help I need I don’t understand it. All of my MRIs And CT milligrams reveal the need to have for strong opioids my scar tissue is Adhered to my spinal nerves. I have shock electric shock that shoots down both legs into my feet and a holler several times a day people at work are used to it. Why won’t we get the help we need when I’m not at work I’m at home in the bed on ice packs the whole time. Please somebody fight for us I’ve never failed a drug test. The pain doctor just acts like he don’t care literally.

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