Etizolam vs. Xanax: What You Need to Know

Mental health issues affect one in every seven people around the world, but unfortunately don’t get the required intervention or counseling as physically acquired disorders. Anxiety disorders are amongst the most common mental health problems that affect people in several ways, from manifesting as physical symptoms to impacting their academic, personal, and social lives. Surveys have shown that 264 million adults worldwide have anxiety, and females with younger people are the most affected.

Anxiety disorders arise in the form of phobias, Generalized Anxiety Disorders,
Obsessive Compulsive Disorders and Post-Traumatic Disorder exhibit the most common symptoms of

• Motor tension

• Apprehension

• Autonomic overactivity

Managing anxiety through medications, counseling, and lifestyle changes is crucial for working on the physical and mental well-being of the individual and enabling them to carry out their day-to-day activities normally.

Etizolam and Xanax are two medications popular for their anxiolytic properties. Both medicines belong to the benzodiazepine class of drugs and are used to provide relief from panic disorders and generalized anxiety. Understanding benzodiazepines better before drawing inferences and comparisons between the two medications and their role in anxiety is essential.

A word about Benzos, and the Working of Etizolam and Xanax

Benzodiazepines are a class of antidepressant drugs that bind to the GABA-A receptors, i.e., inhibitory neurotransmitters in the CNS, to bring out their therapeutic properties. GABA-A receptors are composed of five subunits, e.g., alpha, beta, gamma, delta, epsilon, and rho. A common GABA-A receptor in the CNS consists of two alpha-1 subunits, two beta-2 subunits, and one gamma-2 subunit.

The benzodiazepine binding site is between the alpha-1 and gamma-2 subunits. Animal studies have suggested that the alpha-1 subunit mediates the sedation, amnesia, and ataxic effects of benzodiazepines, and alpha-2 and alpha-3 subunits mediate the anxiolytic and muscle-relaxing effects of benzodiazepines. Also, research suggests that BNZ-1 receptors affect sedation and anti-anxiety, while BNZ-2 affects muscle relaxation, anticonvulsant activity, memory, and motor coordination.

Both Etizolam and Alprazolam (the active ingredient of Xanax) attach themselves to the GABA-A receptors and enhance the effects of GABA by increasing GABA affinity at receptors. When bound to the GABA-A receptor, the major inhibitory neurotransmitter GABA mediates the calming or inhibitory effects on the human nervous system.

Chemical structure and Potency

Etizolam and Xanax have similar actions but different chemical structures that impact their potency. Etizolam is, by nature, a thieno diazepine that mimics the action of benzodiazepines while having a thiophene ring replacing a benzene ring. Xanax is, by nature, a triazole benzodiazepine. The difference in structure results in different half-lives of the drugs with subsequent impact on their effectiveness

Etizolam has a plasma half-life of 3.5 hours, with its active metabolite alpha-hydroxy etizolam having a half-life of 8 hours. Xanax has a plasma half-life of 11 hours and stays in the system much longer before its subsequent elimination through metabolic wastes.

Effectiveness in Anxiolytic activity

Etizolam has been proven to be ten times more potent than Xanax, which has a quicker onset but shorter duration of action. In a study conducted on 45 patients with generalized anxiety, All drugs displayed equivalent anxiolytic activity after two weeks. Still, Etizolam showed a progressive increase in anxiolytic activity over four weeks of treatment. Etizolam also possessed a more marked antidepressant effect than Alprazolam without any difference in the tolerability of the medication.

Sedative and muscle relaxant properties

Xanax has prominent sedative properties and is often categorized as a tranquilizer and an anxiolytic. The effect of medication on the alpha receptors of GABA is directed in such a manner to make the user feel relaxed, quiet, and sleepy. The sublingual and oral form of Alprazolam, the chief component of Xanax, is often used in diagnostic esophagogastroduodenoscopy and during dental procedures for sedating the patient and reducing pain and discomfort at the time. Studies have shown that Alprazolam produces memory impairment at the dosages necessary to produce clinically significant anxiolysis during oral surgery.

Etizolam, in comparison, has less prominent sedative activities and more prominent anxiolytic and myorelaxant properties, as demonstrated by animal studies. Neurochemical research suggests that Etizolam may have selectivity for the subpopulation of Y-aminobutyric acid type A receptors associated with anxiety (i.e., alpha1, beta2, gamma2), leading it to demonstrate marked effectiveness for anxiety and less effectiveness for inducing sedation or sleepiness in patients. The use of Etizolam for palliative sedation in cancer patients did not show a significant response.

Abuse Potential

Benzodiazepines have, over the years, been associated with a lot of abuse and misuse because of their increased risk of tolerance and abuse potential. In addition to authorized pharmacies and online portals legally dispensing the prescribed benzos, other sources like street-supplied imported pills and unauthorized dark web portals enable abusers to obtain the drugs. Unfortunately, these sources do not always deal with authentic medication, and this, in turn, further increases the complication incidence as a result of using spurious drugs.

Studies about the abuse potential of Etizolam or Xanax are comparatively rare. The few available comparative studies reported that Etizolam may induce less tolerance than lorazepam and may have lesser sedative effects than Alprazolam and diazepam. The lower allosteric potency at the α1 subunit of the GABA-A receptor has been proposed as one reason for the reduced liability of Etizolam to tolerance and dependence.

Side effects

The varied chemical structure and affinity of either drug to a separate subunit in the GABA receptors bring out different side effects of either drug. Xanax or Alprazolam use is associated with nocturnal acid reflux or the tendency to cause acid reflux while you sleep, leading to gastritis. Additionally, it can affect your metabolism and overall stomach functioning, leading to a change or loss in appetite, weight gain, or weight loss.

Conversely, Etizolam is associated with psychiatric issues and intolerance in the elderly. In particular, Etizolam was significantly associated with the development of postoperative delirium in a study conducted on elderly hospitalized cancer patients; Suggesting that Etizolam should be administered to postoperative elderly patients with extreme caution.

Availability

Legal Status and subsequent availability are the chief areas of difference between Etizolam and Xanax. Etizolam has been declared a controlled substance by the WHO and is strictly regulated in several countries, including the US and UK. In the UK, Etizolam has been classified as a Class C drug by the May 2017 amendment to The Misuse of Drugs Act 1971. Though considered the least dangerous of the controlled drugs, it is not readily available in registered pharmacies.
Xanax is a class C drug in the UK and cannot be obtained through the NHS. A private prescription is the only way of getting the drug in the UK, while selected pharmacies dispense Xanax in the US, but you need a prescription to procure them. Further, these prescriptions cannot be filled or refilled more than six months after the date they were issued.

Indication in Pregnancy

The FDA has categorized Alprazolam or Xanax into pregnancy Category D. Category D is given to the drugs where there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing studies in humans. But if required, these drugs can be used in pregnant women if the benefits outweigh the risks.

Etizolam has been categorized into pregnancy Category C, with a chance of fetal risk but insufficient data to back the theory. These drugs can be used in pregnancy if the need arises.

A summary of Etizolam vs. Xanax

• Etizolam is stronger than Xanax in anxiolytic properties but has inferior sedation properties
• Sedation is an important quality of Xanax that makes it an essential medication during medical procedures and minor surgeries
• Studies about Etizolam are much less than that of Xanax, which proves a major hindrance in determining its safety and effectiveness
• Xanax and Etizolam are both controlled drugs, but Xanax is more available than Etizolam. Alternatively, online portals are an efficient way of obtaining the medication while keeping in mind the authenticity of the site
• None of the drugs are advised during pregnancy, but if the need arises can be administered by a health expert for patient safety

References

https://ourworldindata.org/mental-health

https://www.ncbi.nlm.nih.gov/books/NBK538165/#:~:text=Mechanism%20of%20Action,-Alprazolam%20belongs%20to&text=Alprazolam%20is%2080%25%20bound%20to%20serum%20protein%2C%20mainly%20albumin.&text=Alprazolam%20is%20metabolized%20in%20the,hydroxyalprazolam%20and%20alpha%2Dhydroxyalprazolam%20metabolites.&text=Alprazolam%20and%20its%20metabolites%20are,and%20excreted%20in%20the%20urine.

https://pubchem.ncbi.nlm.nih.gov/compound/Etizolam

https://pubmed.ncbi.nlm.nih.gov/2572494/

https://www.sciencedirect.com/science/article/abs/pii/S0278239197902809
https://www.sciencedirect.com/topics/medicine-and-dentistry/palliative-sedation

https://chemm.hhs.gov/pregnancycategories.htm