Can Anxiety Relief Come at the Cost of Cognitive Health?

Benzodiazepines, often referred to as “benzos,” are commonly prescribed medications used to treat conditions such as anxiety and insomnia. These include drugs like Ativan, Xanax, and Clonazepam. In the United States alone, millions of people use these anti-anxiety medications. Over the past decade, research has indicated that prolonged use of these drugs may be associated with addiction and cognitive impairments, including dementia, particularly in individuals aged 60 and above.

For instance, a study published in the British Medical Journal discovered a correlation between dementia and the use of anti-anxiety medications like benzos. The study followed nearly 9,000 older adults for six years after they began using the medication for insomnia or anxiety. The findings suggested that those who used benzos were 51 percent more likely to develop dementia, and the risk increased the longer the drugs were used (1).

Another study compared over 70,000 non-institutionalized Finnish men and women diagnosed with dementia from 2005-2010 with a larger demographic-matched group without dementia (2). The researchers concluded that individuals taking benzodiazepines and related drugs had a slightly increased risk of developing dementia.

The type of benzo taken did not affect the dementia risk. However, many of the individuals taking benzos were also on antidepressants or antipsychotic drugs, which could have also contributed to the development of dementia. The authors advised against the use of benzos, especially in older individuals.

In September 2020, the FDA announced that they would update the "black box warning" for benzodiazepines to include information about the risks of physical dependence, withdrawal reactions, misuse, abuse, and addiction (3). This was in addition to a previous warning about the risks of taking benzodiazepines concurrently with opiates, which could lead to death (4).

While these studies do not establish a cause-and-effect relationship, they do suggest a strong correlation between long-term benzo use and dementia. The mechanism for how long-term use of benzo could lead to cognitive impairments has been unknown.

However, a study published in 2022 shed some light on a possible mechanism by which benzos lead to dementia. Researchers at the Australian Nuclear Science and Technology Organization (ANSTO) conducted a study showing how diazepam, a commonly prescribed benzo, can impair the structural plasticity of dendritic spines, leading to cognitive impairments in mice.

The researchers used a unique lab model called “Guwiyang Wurra-TSPO knockout,” a healthy mouse lacking a protein present in the mitochondrion, the cell’s energy-providing organelle (5). Anti-anxiety drugs like diazepam bind to TSPO on the surface of microglial cell organelles. Microglial cells are the brain’s first immune responders and are implicated in dementia, long COVID, chronic fatigue and other cognitive impairments.

In animal models without TSPO, the physiological impairments associated with cognitive impairment from diazepam use were not observed. In addition, the study found that TSPO-mediated loss of dendritic spines accelerated cognitive decline. This is in contrast to the traditional view that benzos work by enhancing the inhibitory GABA synapses in the brain, thus calming the mind.

Anti-anxiety drugs may promote cognitive decline directly and indirectly in several ways:

1. Impact on microglial cells: For example, promoting the movement of microglial cells interferes with dendritic spines' plasticity (areas in synaptic connections critical for learning, memory, and plasticity).
2. Alteration to brain wiring: Long-term use of benzos alters the complex wiring of the brain. For example, the supporting microglial cells indirectly help maintain the functions of these circuits. Benzos interfere with glial cells.
3. Side-effects of the medications: Benzos have side effects such as confusion, clouded thinking, and memory lapses. These side-effects can make learning, which is essential for protecting the brain against cognitive decline, challenging.
4. Other mechanisms: Although one mechanism has been revealed, other mechanisms may also be involved.

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Unsurprisingly, both the Harvard Health Publishing News and the American Geriatric Association have listed benzos as inappropriate for older adults. Fortunately, other options for treating anxiety exist. Alternative treatments include:

1. Cognitive behavioral therapy (CBT): CBT is a well-established therapeutic approach for anxiety. It focuses on identifying and changing negative thought patterns and behaviors. A trained therapist can guide you through this process.
2. Mindfulness and meditation: Mindfulness practices, such as meditation, deep breathing exercises, prayers, and progressive muscle relaxation, can help reduce anxiety. They promote relaxation and self-awareness.
3. Physical activity: Regular exercise has been shown to reduce anxiety. It releases endorphins, which are natural mood lifters. Physical exercise also keeps the brain fit. Choose an activity you enjoy, whether it’s walking, yoga, dancing, or swimming.
4. Limit caffeine and alcohol and avoid recreational drugs: Alcohol and recreational drugs can exacerbate anxiety. Reducing or avoiding them can make a difference. Caffeine can elicit many of the physiological symptoms that can trigger anxiety, such as rapid heartbeat.
5. Sleep hygiene: Lack of sleep can worsen anxiety. Prioritize good sleep habits, such as maintaining a consistent sleep schedule and creating a relaxing bedtime routine. The authors of an article published in Neurotherapeutics in 2019 recommend that doctors be "very cautious" before prescribing benzos to older people and recommend encouraging good sleep hygiene to alleviate the symptoms of anxiety and insomnia (6).

In conclusion, while further research is needed to categorically conclude that long-term use of benzos causes dementia, the evidence strongly points to the perils of long-term use of benzos. This warning is even more credible after recent studies have shed light on the specific mechanisms by which benzos may lead to cognitive impairment. Fortunately, successful alternative treatments exist.

Note: Do not stop taking your prescribed anti-anxiety medications without consulting with a doctor.