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Ambien Use: What Are the Long-Term Effects ?

Ambien

The active component of the drug Ambien is zolpidem. Zolpidem is a  non-benzodiazepine sedative-hypnotic drug that is prescribed to help people sleep. Immediate-release formulations of zolpidem have a fast onset of action and a relatively short half-life, meaning that the medication works quickly and does not remain in a person’s system very long. This makes Ambien primarily useful in helping people fall asleep or to initiate sleep. The drug is not prescribed to help people stay asleep or maintain sleep unless the drug is prescribed in an extended- or controlled-release form.1Ambient Use: Long term Effects

  • Some research studies suggest that Ambien can also be used as a muscle relaxant and may even be capable of controlling some seizures, although the dosage required for seizure control would be extremely high. However, the drug is not approved by the FDA for these purposes.2
  • Zolpidem and similar pharmaceutical agents (e.g., other so called “z-drugs”) were promoted as an alternative to other prescription sedative-hypnotics more likely to cause physical dependence, such as  benzodiazepines. However, the U.S. Drug Enforcement Administration (DEA)  currently lists zolpidem as a Schedule IV controlled substance, indicating that, though relatively low, there is some risk of abuse and dependence. Thus, products containing zolpidem can only be obtained with a prescription from a physician.

 

How Does Ambien Work?

Like benzodiazepines, zolpidem works to increase the activity of the inhibitory neurotransmitter GABA (gamma-aminobutyric acid). GABA is the primary inhibitory neurotransmitter in the brain. Increased GABA activity is associated with decreased firing rates of neurons within the brain and spinal cord. This accounts for its sedative effects. Though zolpidem appears to be molecularly distinct from benzodiazepines, it influences activity at the GABAreceptor, which is the same receptor that benzodiazepines interact with to exert their effects. With a similar mechanism of action and physical effects profile as benzos, there is also a risk of overdose on high doses of zolpidem products. The benzodiazepine antagonist drug flumazenil reverses some of the sedative effects of drugs that bind to GABA receptors and can be used in cases of an overdose on both benzodiazepines and zolpidem products.3

Prescription Sleep Aids Like Ambien Are for Short-Term Use

One of the reasons these drugs are only designed to be used in the short-term is that tolerance develops very rapidly and people often need significantly higher amounts of the drug in a short time to get the same effects.4 abstract paragraph 1  Sedative-hypnotic drugs like Ambien and benzodiazepines (when indicated for insomnia) are best used as short-term solutions while the person develops behavioral methods to help them initiate and maintain sleep. This could involve the use of behavioral therapy, relaxation training, diaphragmatic breathing, imagery, and other non-pharmaceutical methods.

Short-Term Effects of Ambien

The primary therapeutic effects of Ambien include:5

  • Sedation.
  • Drowsiness.
  • Initiation of sleep.

Side effects may include:5

  • Headache.
  • Memory impairments.
  • Insomnia when the drug is discontinued—commonly referred to as rebound insomnia.
  • Unusual dreams.
  • Parasomnias—abnormal, sometimes complex sleep events.
  • In rare cases, hallucinations.
  • Nausea and heartburn.
  • Light-headedness and/or dizziness.
  • Difficulties with balance.
  • Unsteady gait.
  • Physiological dependence.

Parasomnia

Parasomnias are sleep disorders where individuals engage in activities that they would normally perform while they are awake, but they engage in these activities while they are actually asleep. Zolpidem has been implicated in some cases where people have been driving while asleep, eating while asleep, and even having sex while asleep. These cases are very rare. The most common manifestation of a parasomnia is sleepwalking.6

The use of Ambien with alcohol can increase the risk of parasomnias and other side effects. Misusing the drug (e.g., using it in excess of prescribed parameters) may also contribute to this risk.6

Issues with Memory

Use of drugs that increase the activity of GABA, such as benzodiazepines and zolpidem, may be associated with the development of short-term memory problems.7

Zolpidem is recommended for use with caution in the elderly, as they may be at increased risk for more pronounced cognitive effects, including issues with memory for recent events or with forming new memories.8

Rebound Insomnia

People who stop using Ambien may find that they have issues with insomnia once they discontinue their use of the drug, especially if they have been using higher than recommended doses or consistently using the medication for long periods of time. Rebound insomnia, though troublesome, is usually temporary and may be managed with non-pharmacologically with increased attention on sleep hygiene (e.g., a bedtime routine more conducive to sleep) and other behavioral methods.9

Hallucinations

The development of psychotic behaviors and hallucinations as a result of medicinal use of Ambien appears to be rare, but has been observed in a few cases.10

Exacerbation of Gastroesophageal Reflux Disorder

People who have gastroesophageal reflux disorder (GERD) and use Ambien for extended periods of time may experience exacerbations of their symptoms, particularly at night. Because zolpidem users may be more likely to sleep through a reflux event, gastric acid could remain in the esophagus for longer periods of time and increase the risk for the development of complications—such as esophageal cancer—in some individuals.11

Physical Dependence

  • According to its DEA Scheduling, Ambien has a low potential for dependency and abuse. However, self-medicating or long-term use of Ambien use can result in significant physical and psychological dependence, which increases the risk of withdrawal symptoms when you try to stop using it.5
  • You should not abruptly quit taking Ambien without consulting your doctor, especially if you have taken it for longer than 2 weeks, as this can result in a withdrawal syndrome with symptoms such as shakiness, light-headedness, stomach and muscle cramps, nausea, vomiting, sweating, flushing, tiredness, uncontrollable crying, nervousness, panic attack, difficulty falling asleep or staying asleep, uncontrollable shaking of a part of your body, and rarely, seizures.5

Abuse of Zolpidem Products

According to the Substance Abuse and Mental Health Services Administration (SAMHSA), sedative-hypnotic drugs like zolpidem are commonly misused. About 1.1 million people reported misusing (e.g., overuse of a prescription product) zolpidem in 2015.12

An individual who develops a substance use disorder in connection with zolpidem would be diagnosed with a sedative, hypnotic, or anxiolytic use disorder, according to the American Psychiatric Association’s (APA) diagnostic criteria. To meet the criteria for this diagnosis, you must display at least two of the following signs within a 12 month period, including:13

  • Taking Ambien in larger amounts or for a longer time period than originally intended.
  • Being unable to cut down Ambien use despite your best attempts to do so.
  • Spending much time obtaining, using, and recovering from the effects of the drug.
  • Cravings, or strong desires to use the drug.
  • Failing to meet obligations at work, school, or home due to drug use.
  • Continuing to use despite the social or interpersonal problems associated with such use.
  • Giving up or reducing time spent doing important social, occupational, or recreational activities because of drug use.
  • Being under the influence of the medication in dangerous situations (e.g., driving).
  • Continuing to use knowing that you have a physical or psychological problem that is likely related to Ambien use.
  • Developing tolerance.
  • Experiencing withdrawal symptoms or needing to continue the drug to relieve or avoid the onset of withdrawal.

People who abuse Ambien may have started out using the drug as prescribed, then progressively increased such use. Research indicates that some people who misuse Ambien have escalated their doses to doses as high as 2000 mg per day (as opposed to the prescribed therapeutic doses of 5 or 10 mg.)14

Untreated and chronic substance use disorders are associated with numerous other physical and mental health issues, including an increased risk of certain physical and mental health issues (e.g., depression, an eating disorder, a trauma- or stressor-related disorder, etc.), financial issues, employment issues, relationship issues, legal issues, and significant impairment in everyday functioning.15

Other Potential Long-Term Effects Associated with Ambien

Your ability to drive or operate machinery the day after using Ambien may be impaired due to potential problems with attention and decreased reaction time, even if you feel rested and alert. Additionally, you may have an increased risk of falls, decreased reaction time, and problems with coordination the day after Ambien use.5

Although most people who use Ambien on a long-term basis do not report adverse health effects, some people have reported a wide range of negative gastrointestinal, respiratory, cardiovascular, and central nervous system effects.16 Overdose is also possible, with reported effects ranging from markedly diminished levels of consciousness (e.g., somnolence, coma) to cardiovascular and/or respiratory compromise and death.16 Overdose risks may be significantly increased when Ambien is used in combination with alcohol or other CNS depressant substances.

People who struggle with compulsive misuse of zolpidem products should seek help from a clinician who is trained and has experience in the treatment of addiction. Individuals with substance use disorders often do not experience a resolution of their disorder unless they receive some form of professional intervention for their behavior and engage in a long-term recovery program.

MORE ON LONG-TERM EFFECTS:

References

  1. Norman, J. L., Fixen, D. R., Saseen, J. J., Saba, L. M., & Linnebur, S. A. (2017). Zolpidem prescribing practices before and after Food and Drug Administration required product labeling changesSAGE open medicine5.
  2. FooDB. (2015). Showing Compound Zolpidem (FDB023594).
  3. Has, A., Absalom, N., van Nieuwenhuijzen, P., Clarkson, A., Ahring, P. & Chebib, M. (2016). Zolpidem is a potent stoichiometry-selective modulator of α1β3 GABAA receptors: evidence of a novel benzodiazepine site in the α1-α1 interface. Scientific Reports volume 6, Article number: 28674.
  4. Wright, B. (2016). Repeated Zolpidem Treatment Effects on Sedative Tolerance, Withdrawal, mRNA Levels, and Protein Expression.Theses and Dissertations (ETD). Paper 406.
  5. MedlinePlus. (2019). Zolpidem.
  6. Sanofi-Aventis. (2019). Ambien.
  7. Telis, G. (2013). A Sleep Aid Without the Side Effects.
  8. Neel, A. (2012). What Are the Side Effects of Long-term Use of Xanax and Ambien.
  9. National Sleep Foundation. Sleep Aids and Insomnia.
  10. Raza, M., Kennedy, C. & Latif, S. (2014). Zolpidem may cause visual distortions and other psychotic symptoms. Current Psychiatry, 13(3):31-32.
  11. Gagliardi, G. S., Shah, A. P., Goldstein, M., Denua–Rivera, S., Doghramji, K., Cohen, S., & Dimarino, A. J. (2009). Effect of Zolpidem on the Sleep Arousal Response to Nocturnal Esophageal Acid Exposure. Clinical Gastroenterology and Hepatology7(9), 948–952.
  12. Substance Abuse and Mental Health Services Administration. (2016). Prescription Drug Use and Misuse in the United States: Results from the 2015 National Survey on Drug Use and Health.
  13. American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association.
  14. Licata, S. C., Mashhoon, Y., Maclean, R. R., & Lukas, S. E. (2011). Modest abuse-related subjective effects of zolpidem in drug-naive volunteersBehavioural pharmacology22(2), 160–166.
  15. MedlinePlus. (2018). Substance Use Disorder.
  16. 16. U.S. Food & Drug Administration. (2008). Highlights of Prescribing Information: Ambien.