New research suggests that while long-term use of common anti-anxiety medications may not increase dementia risk, it could be quietly reshaping critical areas of the brain. However, this is just one of many concerning findings about benzodiazepines that have emerged in recent years.

The Anxiety Epidemic

Anxiety disorders affect millions worldwide, with an estimated 301 million people living with anxiety globally as of 2019.¹ In the United States alone, anxiety disorders impact about 40 million adults each year.² This widespread prevalence has led to a significant reliance on anti-anxiety medications, particularly benzodiazepines.

Benzodiazepines: A Double-Edged Sword

Benzodiazepines, including well-known medications like diazepam (Valium), alprazolam (Xanax), and lorazepam (Ativan), are among the most frequently prescribed psychotropic drugs in developed countries. These medications are believed to work by enhancing the effect of gamma-aminobutyric acid (GABA), a neurotransmitter that promotes relaxation and reduces brain activity. But this is a limited view, sometimes called the 'monoamine hypothesis,' and does not do justice to the complexity of neurobiology and known and unknown drug interactions and effects in the brain. 

While sometimes 'effective' for short-term relief of anxiety and insomnia, i.e. symptom suppression, concerns have long existed about the long-term use of benzodiazepines, especially in older adults. Risks of dependence, falls, and potential cognitive decline have been at the forefront of these worries.

Unveiling New Insights

A groundbreaking study published in BMC Medicine has shed new light on the long-term effects of benzodiazepine use on brain health. Led by researchers from the Erasmus University Medical Center, this study aimed to clarify conflicting evidence from previous research regarding the impact of benzodiazepines on cognitive function and brain structure.

The Dementia Question: A Surprising Answer

One of the most striking findings of the study was that benzodiazepine use was not significantly associated with an increased risk of developing dementia. This result contrasts with some earlier studies that had suggested a higher risk. However, it's important to note that a 2018 systematic review and meta-analysis did find a modest increased risk of Alzheimer's disease associated with benzodiazepine use.³

A Subtle but Significant Change

The study's neuroimaging data revealed a more nuanced picture of benzodiazepines' impact on the brain. Long-term use was linked to a subtle reduction in the volume of two critical brain regions:

1. The hippocampus: Crucial for memory formation and spatial navigation.
2. The amygdala: Key in processing emotions, particularly fear and anxiety.

While these brain regions naturally shrink as part of the aging process, the accelerated reduction associated with benzodiazepine use could be a marker of neurodegeneration.

Additional Concerns

Beyond brain structure changes, research has uncovered several other concerning effects of long-term benzodiazepine use:

1. Increased Suicide Risk: Multiple studies have found an association between benzodiazepine use and increased risk of suicidal behavior.^4,5,6 One review concluded that benzodiazepines appear to cause an overall increase in the risk of attempting or completing suicide.⁷
2. Mortality Risk: In patients with schizophrenia, benzodiazepine use has been associated with increased mortality risk.⁸
3. Pregnancy Complications: There may be an increased risk of congenital malformations when benzodiazepines are used in conjunction with antidepressants during pregnancy.⁹
4. Hypertension in the Elderly: Diazepam used as an oral hypnotic has been shown to increase nocturnal blood pressure in elderly individuals.¹⁰
5. Delirium in Children: Benzodiazepines have been identified as an independent and modifiable risk factor for the development of delirium in critically ill children.¹¹

Implications for Anxiety Treatment

The study's findings have significant implications for the use of benzodiazepines, particularly among older adults. While the absence of increased dementia risk is reassuring, the observed reduction in hippocampal and amygdalar volume, along with the other identified risks, underscores the importance of caution when prescribing these medications for extended periods.

A Call for Balanced Approaches

This research highlights the need for balanced approaches to anxiety treatment, especially for long-term management. While benzodiazepines remain popular conventional tools for short-term relief, their prolonged use should be carefully considered in light of these findings. Consider there are a wide range of natural alternatives indexed on the Anxiety Disorders page on Greemmedinfo.com which you can view here.

Alternative Approaches to Anxiety Management

Given the potential risks associated with long-term benzodiazepine use, it's crucial to explore alternative approaches for managing anxiety, particularly for chronic cases. Some evidence-based options include:

1. Cognitive Behavioral Therapy (CBT): A well-established psychotherapy approach that has shown effectiveness in treating anxiety disorders.
2. Mindfulness-Based Stress Reduction (MBSR): This meditation-based program has demonstrated promise in reducing anxiety symptoms.
3. Regular Exercise: Physical activity has been shown to have anxiety-reducing effects and may improve overall mental health.
4. Dietary Modifications: Some studies suggest that a Mediterranean-style diet may be associated with lower rates of anxiety.
5. Herbal Supplements: Certain herbs, such as chamomile and passionflower, have shown potential in reducing anxiety symptoms, though more research is needed. There are dozens you can view here.
6. Ayurvedic Medicine: Some Ayurvedic formulations have shown promise in treating generalized anxiety disorder, potentially offering an alternative to benzodiazepines with fewer side effects.¹²

Conclusion: Balancing Benefits and Risks

The growing body of research on benzodiazepines underscores the complexity of managing anxiety disorders and the importance of weighing the benefits and risks of long-term medication use. However, one thing is for sure, changes to brain structure and other health risks should be front and center whenever a patient and their practitioner is considering the risk/benefit analysis of using these drugs. 

Reference

1. World Health Organization. (2022). Mental Health and COVID-19: Early evidence of the pandemic's impact: Scientific brief, 2 March 2022.

2. Anxiety & Depression Association of America. (2021). Facts & Statistics.

3. Tapiainen V, et al. Acta Psychiatr Scand. 2018;138(2):91-100.

4. Fontanella CA, et al. J Clin Psychiatry. 2016;77(5):661-7.

5. Sung HG, et al. Soc Psychiatry Psychiatr Epidemiol. 2019;54(11):1475-1484.

6. Lavigne JE, et al. J Gen Intern Med. 2019;34(10):2141-2149.

7. Dodds TJ. Prim Care Companion CNS Disord. 2017;19(2):16r02037.

8. Fontanella CA, et al. J Clin Psychiatry. 2016;77(5):661-7.

9. Grigoriadis S, et al. J Clin Psychiatry. 2019;80(4):18r12527.

10. Fogari R, et al. Aging Clin Exp Res. 2019;31(2):261-265.

11. Mody K, et al. Crit Care Med. 2018;46(8):1259-1267.

12. Tubaki BR, et al. J Altern Complement Med. 2012;18(6):612-21.