Zolpidem


Article Author:
Daniel Bouchette


Article Editor:
Judy Quick


Editors In Chief:
Dustin Constant
Donald Kushner


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
3/15/2019 10:19:49 AM

Indications

Zolpidem is a non-benzodiazepine receptor modulator primarily used in the FDA approved short-term treatment of insomnia aimed at patients with difficulty starting sleep. [1][2][3] It improves measures of sleep latency, sleep duration, and reduces the number of awakenings in patients with transient insomnia. It also improves sleep quality in patients with chronic insomnia as well and can act as a minor muscle relaxant. Research also shows it is rapid and effective in restoring brain function in patients who are in a vegetative state after brain injury as the drug has the potential to completely or partially reverse the abnormal metabolism of damaged brain cells. Usually, patients recover if the injury is in non-brain stem areas.

Mechanism of Action

Zolpidem, a non-benzodiazepine hypnotic agent, works as a GABAa receptor chloride channel modulator/agonist that increases GABA inhibitory effects leading to sedation. It also has anticonvulsant, anxiolytic, and minor myorelaxant properties. The GABAa receptor also called also GABA-BZ is found in the sensorimotor cortical regions, globus pallidus, inferior colliculus, pons, ventral thalamic complex, olfactory bulb, cerebellum, and substantial in the brain. The drug upregulates these receptors allowing for the sedative effects leading to the preservation of deep sleep.  [4][5]Differing from benzodiazepines, which non-selectively bind to and activate all BZ receptor subtypes, zolpidem in vitro binds the BZ1 receptor preferentially with a high affinity ratio of the alpha1/alpha5 subunits. The selective binding of zolpidem on the BZ1 receptor may explain the relative absence of myorelaxant and anticonvulsant effects. Overall, zolpidem is not recommended for the general population as first-line treatment because of its high potential for abuse. Drugs like controlled release melatonin and doxepin may be used as first line in addition to proper sleep hygiene and cognitive behavioral therapy.

Administration

Zolpidem is rapidly absorbed by the gastrointestinal tract and has a short half-life in healthy patients. It is administered in 5 mg and 10 mg tablets orally depending on the quality of sleep in which the patient is receiving. Zolpidem is then converted to an inactive metabolite and excreted by the kidneys. Tablets are not scored. Ingestion with or immediately after food intake may slow the effects of this drug.

Elderly patients must receive a 5 mg dosage as their concentrations were found to be higher than young adults during clinical trials. Dosage should be changed in patients with hepatic impairment as the half-life of zolpidem was found to be a multitude of times larger than patient with normal health.  The recommended initial dose is 5 mg for women and either 5 or 10 mg for men, taken only once per night immediately before bedtime with at least 7-8 hours remaining before the planned time of awakening.  Zolpidem clearance is lower in women. [6][7][8]

Patients with end-stage renal failure undergoing dialysis do not need dosage adjustments, as they were not significantly different from patients with renal impairments. Their concentrations, however, should be closely watched on a daily basis.

Pediatric patients should not be given zolpidem as their effectiveness has not been found yet. The research found that hallucinations might occur in a small percentage of pediatric patients who received zolpidem.

Adverse Effects

Some adverse effects include anaphylaxis, changes in behavior, withdrawal, and central nervous system (CNS) depression.

In rare situations, patients have reported tongue, larynx, or glottis swelling in the form of angioedema. Also, patients have reported shortness of breath, airway closure, nausea, and vomiting. If patients report these, do not re-administer patient with the drug. Patients who do experience closure in throat, glottis, or larynx should be sent to the emergency department.

Changes in behavior and abnormal thinking have been reported as well. Patients have been found to show aggressiveness and extroversion that is abnormal for the person's usual behavior.

Similar to patients who have alcohol or drug toxicities, patients have experienced auditory and visual hallucinations associated with strange behavior and agitation.

The patient was also found to experience a behavior called sleep driving, in which the patient drives while not fully awake after intake of sedative-hypnotic with no recollection of the event. Consumption of alcohol or any other CNS depressant was found to increase these events as they enhance sedation when combined. In these cases, the drug needs to be discontinued.

Patients who are depressed should also not take zolpidem as it worsens depression along with suicidal ideations and actions.

Contraindications

It is only contraindicated in patients with a known allergy to the drug or inactive ingredients in the formula. Also before administering zolpidem, other causes of sleep deprivations must be evaluated, for example, any presenting physical or psychiatric histories.

Caution should be used in patients who are also taking drugs that affect drug metabolism via cytochrome P450. Consider giving a lower dosage of zolpidem as patients have shown to enhance sedative effects.

Patients taking imipramine and chlorpromazine should avoid using zolpidem. When combined, these medications cause decreased alertness and psychomotor performance.

Monitoring

The drug elimination half-life for 5 mg of zolpidem was found to be 2.6 hours. Respectively, the elimination for patients who are given 10 mg of zolpidem is 2.5 hours with ranges between 1.4 to 3.8 hours. Zolpidem undergoes a linear pattern of kinetics when the drug dose range is between 5 mg to 20 mg. The drug was also found to be mostly bound to protein and remained unchanged in concentration subsequently extracted through the renal system.

Patients experience anterograde amnesia after drug administration if plasma concentrations are high at the time of stimulus. This is attributed to either inattention or consolidations to memory process.

This drug has a high potential for overuse and daily dependence. Patients with a few weeks drug use have a low behavioral dependency on zolpidem. Patients who used zolpidem in higher single doses or had a history of drug abuse should be monitored carefully when using zolpidem or any other hypnotic.

Toxicity

Drug overdose with zolpidem involves CNS depression, cognitive impairments leading to somnolence or coma, cardiovascular and respiratory depression, and other fatalities. The acute toxicity for zolpidem is less in severity in comparison to other short-acting benzodiazepines like triazolam and midazolam. However, in combined intoxication with other CNS depressant drugs, zolpidem even with a low concentration can induce coma in patients. Single-drug poisoning is benign and should not require therapeutic intervention. 

If a patient shows any symptoms, gastric lavage should only be attempted if within one hour of ingestion, benefits outweigh risks and if the patient is conscious with a gag reflex or intubated. Patients can also benefit from administration with flumazenil and intravenous fluids as well. Flumazenil is a known reversal agent to benzodiazepine toxicity; however, can contribute to the exacerbations of other neurological symptoms such as convulsive activity.

In the event of drug toxicity, the patient's respiratory function, oxygen saturation, blood pressure, pulse, and other vitals should be monitored.[9]

Enhancing Healthcare Team Outcomes

Managing insomnia and zolpidem use requires an interprofessional team of healthcare professionals that includes a pharmacist, a therapist, a nurse, and a physician. Without proper management, significant drug-drug interactions may occur. CNS depression is increased with the combination of opiates, benzodiazepines, antidepressants or alcohol. Because the drug has the potential to cause dependence, it should not be prescribed for long periods. In addition, the patient should be told to avoid alcohol and other CNS depressants when taking zolpidem.


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Zolpidem - Questions

Take a quiz of the questions on this article.

Take Quiz
A 54-year-old male with a history of insomnia comes into the clinic for a routine examination. He stated that he no longer feels the need to use zolpidem anymore. His sleeping improved compared to a couple of months ago. Which of the following is the mechanism of action for this drug?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 44-year-old patient comes to the clinic as a new patient. When asked for her medications list, she states that she used to take a sleeping pill due to insomnia, prescribed by her last doctor. However, she no longer takes it as they were causing her to feel tired during the day. Which drug was this patient most likely prescribed in the past?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 34-year-old with past medical history of insomnia comes to the clinic with complaints of daytime drowsiness and problems staying asleep. She is currently taking temazepam, and is looking for a different medication. What is the most appropriate treatment for this patient?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
The drug zolpidem belongs to which medication classification?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the most common adverse effect of using zolpidem?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Zolpidem - References

References

Sharma MK,Kainth S,Kumar S,Bhardwaj A,Agarwal HK,Maiwall R,Jamwal KD,Shasthry SM,Jindal A,Choudhary A,Anand L,Dhamija RM,Kumar G,Sharma BC,Sarin SK, Effects of zolpidem on sleep parameters in patients with cirrhosis and sleep disturbances: A randomized, placebo-controlled trial. Clinical and molecular hepatology. 2019 Mar 11;     [PubMed]
Kim HM,Gerlach LB,Van T,Yosef M,Conroy DA,Zivin K, Predictors of Long-Term and High-Dose Use of Zolpidem in Veterans. The Journal of clinical psychiatry. 2019 Feb 5;     [PubMed]
Bjurström MF,Irwin MR, Perioperative Pharmacological Sleep-Promotion and Pain Control: A Systematic Review. Pain practice : the official journal of World Institute of Pain. 2019 Feb 14;     [PubMed]
Nigam G,Camacho M,Riaz M, The effect of nonbenzodiazepines sedative hypnotics on apnea-hypopnea index: A meta-analysis. Annals of thoracic medicine. 2019 Jan-Mar;     [PubMed]
Neumann E,Rudolph U,Knutson DE,Li G,Cook JM,Hentschke H,Antkowiak B,Drexler B, Zolpidem Activation of Alpha 1-Containing GABA{sub}A{/sub} Receptors Selectively Inhibits High Frequency Action Potential Firing of Cortical Neurons. Frontiers in pharmacology. 2018;     [PubMed]
McDonagh MS,Holmes R,Hsu F, Pharmacologic Treatments for Sleep Disorders in Children: A Systematic Review. Journal of child neurology. 2019 Jan 23;     [PubMed]
Expanded table: Some oral hypnotics for chronic insomnia. The Medical letter on drugs and therapeutics. 2018 May 7;     [PubMed]
Drugs for chronic insomnia. The Medical letter on drugs and therapeutics. 2018 Dec 17;     [PubMed]
Geulayov G,Ferrey A,Casey D,Wells C,Fuller A,Bankhead C,Gunnell D,Clements C,Kapur N,Ness J,Waters K,Hawton K, Relative toxicity of benzodiazepines and hypnotics commonly used for self-poisoning: An epidemiological study of fatal toxicity and case fatality. Journal of psychopharmacology (Oxford, England). 2018 Jun;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Surgery-Podiatry Cert Medicine. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Surgery-Podiatry Cert Medicine, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Surgery-Podiatry Cert Medicine, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Surgery-Podiatry Cert Medicine. When it is time for the Surgery-Podiatry Cert Medicine board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Surgery-Podiatry Cert Medicine.