Anxiety Medications Causing More Harm Than Good?

Benzodiazepines are a class of medications used to treat conditions such as anxiety and insomnia. In 1955, the first benzodiazepine (BZD), chlordiazepoxide (Librium), was developed, followed by diazepam (Valium) in 1963. (1) Prescriptions skyrocketed and BZD became part of popular culture and were even referenced by the Rolling Stones song, “Mother’s Little Helper.” It wasn’t until the 1980s that concerns about their highly addictive properties began to surface. Despite this concern, in 2019, an estimated 92 million benzodiazepine prescriptions were dispensed from U.S. outpatient pharmacies, with alprazolam (38%) being the most common followed by clonazepam (24%) and lorazepam (20%). (2) It appears that the use of BZD has increased in the U.S. and around the world during the COVID pandemic / lockdown. (3-5) What impact will this have in our future?

Scientist have known for a long time that long-term use of BZD for the treatment of anxiety or panic disorder can increase the risk of cognitive impairment or dementia later in life. The mechanisms of these changes had previously been unknown. A study in 2022 demonstrated in an animal model that BZD damage microglial cells, which then interfere with the synaptic connections that allow parts of the brain to communicate with other regions. (6) When this communication is disrupted, cognitive decline can occur.

Having anxiety or a panic attack feels awful, and therefore most patients are looking for a quick relief. What if that quick fix comes with serious consequences down the road, would you still consider using it? So, what are the risks of long-term BZD use?

• Dependence and addiction: For many people, it can be difficult to stop taking anti-anxiety medications. Many patients find BZD harder to get off than opioid medications. (7)

• Cognitive status: BZDs can lead to generalized impairment of cognition, including attention, learning, and memory. Many studies have demonstrated an increased risk of cognitive decline and dementia with long term use of BZD. (8)

• Sleep effects: BZD are commonly used to treat insomnia in the short term but worsen sleep in the long term. These drugs disrupt sleep architecture, decreasing sleep time and REM sleep. (9)

• Accidental overdose: Many people take BZD in addition to pain medications, such as opioids, alcohol, or sleeping medication. These combinations can be fatal in some instances.

• Suicidal behavior: Use of BZDs are associated with an increased rate of suicide. (10)

Given all these potentially serious consequences, it is recommended to try alternatives to BZD whenever possible. Taking a pill to control your anxiety is tricking your brain to think that only an external stimulus can control the anxiety symptoms. But what if I told you there are numerous ways you can control this stimulus from within? If you look at the pharmacokinetics of BZD, time to peak plasma concentration for the fastest acting oral formulations is 30-60 mins. (11) There are other techniques, such as breathing exercises, that work faster than that! I think another thing to keep in mind is that feeling is normal. Learning to better recognize and understand our feelings and emotions is key to staying balanced, focused, and in control, no matter what challenges you face in life. Let’s look at some tips to control anxiety naturally.

!!!!!If you have been on a BZD for a long time, do not stop taking them abruptly as this can have serious side effects. Work with your physician to gradually taper off the medication.!!!!!

Natural ways to soothe anxiety:

Practice deep breathing: I personally like the 4-7-8 breath but any breathing technique where your exhale is longer than your inhale will work as it stimulates the vagus nerve. The 4-7-8 breath is based on pranayama breathing exercise, an ancient yogic practice. Pranayama shifts the autonomic nervous system from the fight or flight sympathetic to the calming parasympathetic state. (11) You can practice this breath anytime and anywhere. When first starting, try to do this twice a day, but you can do as often as you need. Start with four cycles until you get used to it, then you can work your way up to eight cycles. You may feel lightheaded at first, but this will pass. This breathing technique will become more powerful as you use it.

1. Find a comfortable place to sit with your back straight.

2. Place your tongue against the back of your top teeth and keep it there.

3. Exhale completely through your mouth around your tongue, making a whoosh sound. Purse your lips if it helps.

4. Close your lips and inhale through your nose for a count of four.

5. Hold your breath for a count of seven.

6. Exhale completely through your mouth making a whoosh sound for a count of eight.

7. This completes one cycle. Repeat for three more cycles.

Practice meditation, prayer, or self-hypnosis: All 3 of these have been shown to help calm stress and anxiety. The key here is finding a practice or technique that feels comfortable for you. All these techniques are used as ways to reflect on yourself and achieve a higher sense of awareness, calming the mind, and letting go of negative thoughts.

Practice positive thinking: Positive thinking starts with self-talk. Negative thinking can infest your mind and fuel anxiety. Surround yourself with positive people. Negative people may increase your stress level and make you doubt your ability to manage stress in healthy ways.

Eat a balanced diet: There is a significant relationship between mood and blood sugar. Symptoms of poor glycemic regulation, big swings in blood sugar, have been shown to mirror mental health symptoms such as irritability, anxiety, and worry. Try to reduce intake of refined carbohydrates, processed foods, and sweets and focus on increasing vegetables, fruits, fiber, and protein.

Stay active: Exercise releases neurotransmitters, endorphins, endocannabinoids, and dopamine, which can improve mood. Exercise also promotes neuroplasticity and increased oxygen supply to your brain.

Limit caffeine: Caffeine is the most commonly used psychoactive substance in the world. It can cause nervousness, restlessness, or irritability, neither of which is good for anxiety. Caffeine excites brain cells, causing the pituitary gland to think there is an emergency and in turn it signals the adrenals to release adrenaline.

Try aromatherapy: Numerous studies have demonstrated that aromatherapy can improve mood and lessen anxiety. (13) The most effective methods are aromatic massage and aromatherapy therapy with lavender essential oil.

Take calming nutritional supplements: Several nutraceuticals and botanicals -GABA, l-theanine, magnesium, passionflower, and kava to name a few-have evidence that they can be beneficial for anxiousness or stress. (14)

Hope these tips can help you learn to manage the stress in your life!

Stay well!

Reference:

1. Wick, J.Y. (2013). The history of benzodiazepines. The Consultant Pharmacist, 28(9), 538-548.

2. U.S. Food & Drug Administration. (September 23, 2020). FDA requiring labeling changes for benzodiazepines. https://www.fda.gov/news-events/press-announcements/fda-requiring-labeling-changes-benzodiazepines

3. Niles, J.K., Gudin, J., Radcliff, J., & Kaufman, H.W. (2021). The opioid epidemic within the COVID-19 pandemic: drug testing in 2020. Population Health Management, 24(S1), S43-S51.

4. Gili, A., Bacci, M., Aroni, K., Nicoletti, A., Gambelunghe, A., Mercurio, I., & Gambelunghe, C. (2021). Changes in drug use patterns during the COVID-19 pandemic in Italy: monitoring a vulnerable group by hair analysis. International Journal of Environmental Research and Public Health, 18(4), 1967.

5. Yu, C., Boone, C., Askarian-Monavvari, R., & Brown, T. (2021). Trends in pharmacotherapy for anxiety and depression during COVID- 19: a North York area pilot study. University of Toronto Medical Journal, 98(1), 41-46.

6. Shi, Y., Cui, M., Ochs, K., Brendel, M., Strubing, F.L., Briel, N., Eckenweber, F., Zou, C., Banati, R.B., Liu, G.J., Middleton, R.J., Rupprecht, R., Rudolph, U., Zeilhofer, H.U., Rammes, G., Herms, J., & Dorostkar, M.M. (2022). Long-term diazepam treatment enhances microglial spine engulfment and impairs cognitive performance via the mitochondrial 18 kDa translocator protein (TSPO). Nature Neuroscience, 25, 317–329.

7. Longo, L.P., & Johnson, B. (200). Addictions: Patr I. Benzodiazepines-side effects, abuse risk, and alternatives. American Family Physician, 61(7), 2121-2128.

8. He. Q., Chen, X., Wu, T., Li, L., & Fei, X. (2019). Risk of dementia in long-term benzodiazepine users: Evidence from a meta-analysis of observational studies. Journal of Clinical Neurology, 15(1), 9-19.

9. Ribeiro de Mendonça, F.M., Ribeiro de Mendonça, G.P.R., Souza, L.C., G,alvão, L.P., Paiva, H.S., de Azevedo Marques Périco, C., Torales, J., Ventriglio, A., Castaldelli-Maia, J.M., Silva, A.S.M. (2021). Benzodiazepines and Sleep Architecture: a systematic review. CNS & Neurological Disorders Drug Targets. doi: 10.2174/1871527320666210618103344.

10. Dodds, T.J. (2017). Prescribed benzodiazepines and suicide risk: A review of the literature. The Primary Care Companion for CNS Disorders, 2(2). doi: 10.4088/PCC.16r02037

11. Griffin III, C.E., Kaye, A.M., Rivera Bueno, F., & Kaye, A.D. (2013). Benzodiazepine pharmacology and central nervous system-mediated effects. The Oshsner Journal, 13(2), 214-223.

12. Jerath, R., Edry, J.W., Barnes, V.A., & Jerath, V. (2006). Physiology of long pranayamic breathing: neural respiratory elements may provide a mechanism that explains how slow deep breathing shifts the autonomic nervous system. Medical Hypotheses, 67(3), 566-571.

13. Gong, M., Dong, H., Tang, Y., Huang, W., & Lu, F. (2020). Effects of aromatherapy on anxiety: A meta-analysis of randomized controlled trials. Journal of Affective Disorders, 274, 1028-1040.

14. Srivastava, Aa., & Kumar,. P. (2021). Nutraceutical in anxiety and stress. Nutraceuticals, (2nd ed), Academic Press.