Benzodiazepines

Overview of Benzodiazepines

Benzodiazepines are a type of depressant that induces sedation, promotes sleep, alleviates anxiety and muscle spasms, and helps control seizures [1]. Benzodiazepines act on receptors in the central nervous system [2]. They can be prescribed for a range of conditions, including insomnia, acute status epilepticus, inducing amnesia, agitation, anxiety, as well as spastic and seizure disorders [2]. Benzodiazepines share a fundamental chemical structure and work by enhancing the activity of gamma-aminobutyric acid (GABA) receptors, a neurotransmitter that suppresses neuronal activity, thereby calming the brain and nervous system [15]. The primary differences among benzodiazepines lie in their absorption rate, duration of effects, and the time required for the body to eliminate them [15].

Examples of benzodiazepines

Commonly prescribed benzodiazepines include Valium, Xanax, Halcion, Ativan, and Klonopin [1]. For managing insomnia, shorter-acting options like estazolam (ProSom), flurazepam (Dalmane), temazepam (Restoril), and triazolam (Halcion) are frequently used [1]. Additionally, midazolam (Versed), a short-acting benzodiazepine, is often employed for sedation, anxiety relief, and inducing amnesia in critical care settings and before anesthesia [1].

• Alprazolam: Prescribed for anxiety and panic disorders, including agoraphobia [3].

• Chlordiazepoxide: Mainly used to manage alcohol withdrawal syndrome [4].

• Clobazam: Indicated for seizures linked to Lennox-Gastaut syndrome [5].

• Clonazepam: Used to treat panic disorder, agoraphobia, myoclonic seizures, and absence seizures [3][6].

• Clorazepate: Applied as adjunctive therapy for short-term management of anxiety disorders and for focal (partial) onset seizures [7].

• Diazepam: Employed in managing alcohol withdrawal, with rectal forms used for febrile seizures [7][8].

• Estazolam: Recommended by the American Academy of Sleep Medicine for insomnia treatment [9].

• Flurazepam: Indicated for treating insomnia [9].

• Lorazepam: Used for anxiety disorders and is a first-line treatment for convulsive status epilepticus, as per American Epilepsy Society guidelines [10].

• Midazolam: Indicated for convulsive status epilepticus and procedural sedation, also used for sedation in mechanically ventilated patients in intensive care units [11].

• Oxazepam: Prescribed for anxiety disorders and recommended for alcohol withdrawal syndrome by the American Society of Addiction Medicine [12].

• Quazepam: The American College of Physicians recommends quazepam for treating chronic insomnia in adults [13].

• Temazepam: Suggested by the American Academy of Sleep Medicine for both sleep onset and sleep maintenance insomnia [9].

• Triazolam: Primarily indicated for sleep-onset insomnia.

• Remimazolam: Approved by the FDA in 2020 for short procedural sedation (under 30 minutes) in adults [14].

Ways benzodiazepines are overdosed

Misuse is commonly seen among adolescents and young adults who consume the drug orally or crush and snort it to achieve a high [1]. This behavior is especially prevalent among heroin and cocaine users [1]. Additionally, individuals using opioids often co-abuse benzodiazepines to intensify feelings of euphoria [1].

Side effects of Benzodiazepine

1. Respiratory depression [2]

2. Respiratory arrest [2]

3. Drowsiness [2]

4. Confusion [2]

5. Headache [2]

6. Syncope [2]

7. Nausea [2]

8. Vomiting [2]

9. Diarrhea [2]

10. Tremors [2]

Effect of Benzodiazepine overdose

1. Drowsiness [1]

2. Confusion [1]

3. Impaired coordination [1]

4. Decreased reflexes [1]

5. Respiratory depression [1]

6. Coma [1]

7. Death [1]

References

1. United States Drug Enforcement Administration. (n.d.). Benzodiazepines. Dea.gov. https://www.dea.gov/factsheets/benzodiazepines

2. Bounds, C. G., & Patel, P. (2024, January 30). Benzodiazepines. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK470159/

3. Garakani, A., Murrough, J. W., Freire, R. C., Thom, R. P., Larkin, K., Buono, F. D., & Iosifescu, D. V. (2020). Pharmacotherapy of anxiety disorders: Current and emerging treatment options. Frontiers in Psychiatry, 11, 595584. https://doi.org/10.3389/fpsyt.2020.595584

4. March, K. L., Twilla, J. D., Reaves, A. B., Self, T. H., Slayton, M. M., Bergeron, J. B., & Sakaan, S. A. (2019). Lorazepam versus chlordiazepoxide for the treatment of alcohol withdrawal syndrome and prevention of delirium tremens in general medicine ward patients. Alcohol, 81, 56–60. https://doi.org/10.1016/j.alcohol.2019.05.003

5. Isojarvi, J., Gidal, B. E., Chung, S., & Wechsler, R. T. (2018). Optimizing clobazam treatment in patients with Lennox-Gastaut syndrome. Epilepsy & Behavior, 78, 149-154.

6. Brigo, F., Igwe, S. C., Bragazzi, N. L., & Lattanzi, S. (2019). Clonazepam monotherapy for treating people with newly diagnosed epilepsy. Cochrane Database of Systematic Reviews, 2019(11).

7. Riss, J., Cloyd, J., Gates, J., & Collins, S. (2008). Benzodiazepines in epilepsy: Pharmacology and pharmacokinetics. Acta Neurologica Scandinavica, 118(2), 69-86.

8. Chiang, L. M., Wang, H. S., Shen, H. H., Deng, S. T., Tseng, C. H., Chen, Y. I., Chou, M. L., Hung, P. C., & Lin, K. L. (2011). Rectal diazepam solution is as good as rectal administration of intravenous diazepam in the first-aid cessation of seizures in children with intractable epilepsy. Pediatrics and Neonatology, 52(1), 30-33.

9. Sateia, M. J., Buysse, D. J., Krystal, A. D., Neubauer, D. N., & Heald, J. L. (2017). Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: An American Academy of Sleep Medicine clinical practice guideline. Journal of Clinical Sleep Medicine, 13(2), 307-349.

10. Glauser, T., Shinnar, S., Gloss, D., Alldredge, B., Arya, R., Bainbridge, J., Bare, M., Bleck, T., Dodson, W. E., Garrity, L., Jagoda, A., Lowenstein, D., Pellock, J., Riviello, J., Sloan, E., & Treiman, D. M. (2016). Evidence-based guideline: Treatment of convulsive status epilepticus in children and adults: Report of the guideline committee of the American Epilepsy Society. Epilepsy Currents, 16(1), 48-61.

11. Devlin, J. W., Skrobik, Y., Gélinas, C., Needham, D. M., Slooter, A. J. C., Pandharipande, P. P., Watson, P. L., Weinhouse, G. L., Nunnally, M. E., Rochwerg, B., Balas, M. C., van den Boogaard, M., Bosma, K. J., Brummel, N. E., Chanques, G., Denehy, L., Drouot, X., Fraser, G. L., Harris, J. E., … Alhazzani, W. (2018). Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Critical Care Medicine, 46(9), e825-e873

12. The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management. (2020). Journal of Addiction Medicine, 14(3S Suppl 1), 1-72

13. Qaseem, A., Kansagara, D., Forciea, M. A., Cooke, M., & Denberg, T. D. (2016). Management of chronic insomnia disorder in adults: A clinical practice guideline from the American College of Physicians. Annals of Internal Medicine, 165(2), 125-133

14. Kilpatrick, G. J. (2021). Remimazolam: Non-clinical and clinical profile of a new sedative/anesthetic agent. Frontiers in Pharmacology, 12, 690875

15. Harvard Health. (2020, September 27). Benzodiazepines (and the alternatives). https://www.health.harvard.edu/mind-and-mood/benzodiazepines_and_the_alternatives#:~:text=Benzodiazepines%20have%20a%20common%20basic,the%20brain%20and%20nervous%20system.