Benzos like Xanax may shrink the brain in the long term, study hints

Two boxes of Xanax lying side-by-side, pointing towards the camera. They appear to be positioned on top of a wooden table. The box on the left is open and packets of pills are sliding out of it towards the camera.
Benzodiazepines like Xanax, pictured above, relax the nervous system and are widely used to treat conditions such as anxiety and insomnia. However, new research suggests that they may also accelerate brain tissue loss. (Image credit: BSIP / Contributor via Getty Images)

Long-term use of benzodiazepines may shrink certain parts of the brain, new research suggests. 

The findings support current guidelines on the use of this class of drugs, which caution against using benzodiazepines for extended periods of time. 

Benzodiazepines, also known as "benzos," are sedative drugs commonly prescribed to treat numerous conditions, including insomnia, anxiety and seizure disorders. They work by slowing down the activity of the central nervous system, meaning the brain and spinal cord. This can relax a person's mood, relieve muscle spasms and also cause people to feel sleepy. 

These drugs, which include Xanax, are highly addictive and previous research has shown that long-term use comes with a risk of memory and movement issues. As such, the U.S. Food and Drug Administration (FDA) recommends that benzodiazepines are prescribed at the lowest dose possible and for the minimum time required to achieve the desired clinical effects — usually around two to four weeks

Despite these concerns, evidence suggests that between 6% and 15% of patients prescribed benzodiazepines use the drugs for more than six months.

In the new study, published Monday (July 1) in the journal BMC Medicine, researchers have revealed another reason to be cautious about prolonged benzo use: it use may speed up the natural age-related dwindling of two regions of the brain involved in memory and mood regulation, called the hippocampus and the amygdala

Related: Scientists debunk myth that human brains are 'underdeveloped' at birth

The researchers reviewed the medical records of 5,443 adults in the Netherlands who initially had no reported cognitive impairment. The scientists scanned the medical records to determine if, and how many, benzodiazepines the individuals had taken daily between 1991 and 2008. On average, people took their prescribed daily dose 37 times within this time frame. 

The team found that around 50% of study participants had used benzodiazepines at some point up to 2008, and approximately 13% of the overall group went on to be diagnosed with dementia by 2020. Notably, the people who took benzodiazepines were no more likely to develop dementia than those who'd never taken them, regardless of how much they took and for how long, the team found. 

These findings contradict two prior analyses conducted by different groups of researchers. These past analyses summed up the findings of numerous studies on the topic — however, those studies differed in how they were conducted, and their differences might have muddied the results, the team said. 

Although the new study didn't find that benzos boosted dementia risk, it did uncover physical brain changes tied to the drugs. The researchers looked at brain scans that were taken at least once from roughly 4,800 of the 5,443 participants. These scans showed changes in the volume of different structures in the brain over time. 

Based on these scans, the researchers concluded that benzodiazepine use was associated with an accelerated reduction in the volume of the hippocampus and amygdala. In other words, these structures shrunk faster in the group who took benzos, compared to the group who had not used the drugs. 

In addition to these changes in overall brain volume, the team uncovered differences in white matter, the brain tissue that contains the passageways that transmit signals between neurons. Participants who took benzodiazepines specifically for sleep issues — known as sedative-hypnotics — showed a faster reduction in white matter volume than those who took benzodiazepines for anxiety, called anxiolytics.

"Our results underline guidelines that say that you shouldn't take benzodiazepines for a very long period of time," Ilse vom Hofe, co-senior study author and a doctoral candidate at Erasmus University Medical Center in The Netherlands, told Live Science. "Also, I think it motivates health clinicians to look into other therapies to address the problems that people are experiencing, instead of just riding out the benzodiazepines."

The team acknowledged several limitations of the new study. For instance, they only looked at people who started out "cognitively healthy," so it's unclear whether benzos might have more or less profound impacts in people with cognitive impairment. Participants were also mainly white, which may limit how well the findings apply to additional groups. 

As they stand, though, the findings support the need for more research investigating the impact of long-term benzodiazepine use on brain health, the team said. 

This article is for informational purposes only and is not meant to offer medical advice.

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Emily Cooke
Staff Writer

Emily is a health news writer based in London, United Kingdom. She holds a bachelor's degree in biology from Durham University and a master's degree in clinical and therapeutic neuroscience from Oxford University. She has worked in science communication, medical writing and as a local news reporter while undertaking journalism training. In 2018, she was named one of MHP Communications' 30 journalists to watch under 30. (