Benzodiazepine Use Linked to Miscarriage; Stopping the Drugs After Long-Term Use Increased Risk of Fatality, New Research Finds

Mental health watchdog CCHR presses for DEA reclassification of benzodiazepines due to risks of physical dependency and addiction.

by CCHR National Affairs Office

The use of benzodiazepines during pregnancy increases the risk of miscarriage, new research has indicated.  A separate study unexpectedly found that long-term benzodiazepine users face a greater risk of dying after discontinuing the drugs than continuing to take the drugs, calling into question long-term benzodiazepine treatment.  Researchers involved in the studies advised prescribers to carefully consider these potential harms when making treatment decisions about whether to start patients on benzodiazepines.

Benzodiazepines are a class of psychiatric drugs used as treatment for anxiety, panic attacks, and insomnia.  Commonly prescribed benzodiazepines include Xanax, Klonopin, Ativan and Valium.

Studies on an association between benzodiazepines and miscarriage were limited until recently.  Researchers in Taiwan analyzed health and birth certificate records to identify pregnancies that ended in miscarriage between 2004 and 2018, looking for a potential association with benzodiazepine use. 

They found that the risk of miscarriage was 69% greater for those taking benzodiazepines than those who were not.  The increased risk of miscarriage was found with all commonly used benzodiazepines.

“The use of benzodiazepines during pregnancy was associated with an increased risk of miscarriage,” wrote lead author Lin-Chieh Meng, MS, of the Graduate Institute of Clinical Pharmacy, National Taiwan University, Taipei, Taiwan.  The study was reported in JAMA Psychiatry.

There also had been no studies dedicated to investigating the risk to benzodiazepine users of discontinuation until recently.  A new study unexpectedly found that long-term benzodiazepine users face a greater risk of death from discontinuing than continuing the drugs.  The incidence of death from any cause over the year following discontinuation of benzodiazepine use was 5.5% as compared to 3.5% for those who did not stop taking the drugs.  This equates to a risk of mortality 1.6 times greater for those who discontinued benzodiazepines than for those who did not, the researchers wrote.

Compared to those who continued benzodiazepines, those who stopped also faced greater risks of suicidal ideation, suicide attempt or self-inflicted injury, nonfatal overdose, and emergency department use, the researchers found. 

“It is possible that, having become physiologically dependent on benzodiazepines, patients experience adverse outcomes from withdrawal,” they wrote, reporting in JAMA Network Open.

These results are especially concerning in light of what the researchers say is “interest in reducing long-term benzodiazepine prescribing given harms associated with use.” 

From 2015-2016, over 10% of U.S. adults reported benzodiazepine use at some time in the prior year, and use had been increasing over the prior two decades.  In 2019, an estimated 92 million benzodiazepine prescriptions were dispensed from U.S. outpatient retail and mail-order pharmacies, according to the U.S. Food and Drug Administration (FDA).

The medical literature has extensive evidence of the risks associated with benzodiazepine use, including drowsiness, fatigue, weakness, impaired coordination, impaired memory, confusion, irritability, and decreased sex drive.  The U.S. Drug Enforcement Administration (DEA) lists the effects of the drugs on the mind as amnesia, hostility, irritability, and vivid or disturbing dreams.

Discontinuing the drugs can be dangerous.  The FDA warns that “stopping benzodiazepines abruptly or reducing the dosage too quickly can result in serious withdrawal reactions, including seizures, which can be life-threatening.” 

The FDA further advises that even when the benzodiazepine dosage is decreased gradually, patients may experience abnormal involuntary movements, anxiety, blurred vision, memory problems, irritability, insomnia, muscle pain and stiffness, panic attacks, and tremors.  More serious withdrawal symptoms include seizures, hallucinations, mania, psychosis, depression and suicidal thoughts.  Withdrawal symptoms can last many months, the FDA says.

Along with an increasing number of benzodiazepine users is a growing number of overdoses and overdose deaths.  After opioids, benzodiazepines are the prescription drugs most involved in overdose deaths.  In 2020, as benzodiazepine-involved overdose deaths reached a record high in the U.S., the FDA updated the black box warning on the package inserts for benzodiazepines to include warnings about “the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions.” 

In light of the FDA’s updated warning about dependence and addiction, the Citizens Commission on Human Rights (CCHR) has called on the DEA to align with the FDA and change the classification of benzodiazepines, which are still classifed as Schedule IV drugs.  Schedule IV drugs are defined by the DEA as “drugs with a low potential for abuse and low risk of dependence.”  The classification is clearly at odds with the FDA’s findings.

WARNING: Anyone wishing to discontinue or change the dose of a benzodiazepine or other psychiatric drug is cautioned to do so only under the supervision of a physician because of potentially dangerous withdrawal symptoms.

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