Zolpidem (Ambien, Edluar, Zolpimist)

This article provides an overview of zolpidem, including how it works, its indications, side effects, interactions, and precautions.

Key Takeaways:

• Zolpidem is a prescription sedative-hypnotic medication used for insomnia, especially for individuals who have difficulty falling asleep. It works by increasing the effects of GABA, which helps calm down mental activity.

• Zolpidem works quickly and is primarily used for short-term. Long-term use (such as greater than several weeks) is typically not recommended due to the potential for dependence and, in some cases, addiction.

• Zolpidem has many possible side effects, some of which may be dangerous or life-threatening. There are also potentially harmful interactions with other CNS depressants and a variety of other medications.

Understanding Zolpidem

Zolpidem belongs to a class of medications called non-benzodiazepine sedative-hypnotics (also called “Z-drugs” for short). Like other Z-drugs, zolpidem exerts calming activities in the brain, which may help with sleep. It is used mainly on a short-term basis for insomnia, especially for individuals who have trouble falling asleep. ^[1]

How Zolpidem Works

Insomnia often has many factors, but it is often due at least partially to overactivity or hyperarousal in the brain and nervous system, which makes it difficult to initiate sleep.

Therefore, zolpidem is designed to target insomnia by slowing down activity in the brain and nervous system. Specifically, zolpidem increases the effects of GABA by binding to specific GABA receptors in the brain. Since GABA is an inhibitory neurotransmitter, these effects lead to sedation, relaxation, and sleep promotion. ^[1]

Brand Names

The most common brand name for zolpidem is Ambien® (also formulated as Ambien® CR). Other brand names of zolpidem are: ^[2]

• Edluar®

• Zolpimist®

• Intermezzo®

What is Zolpidem Used For?

Zolpidem is approved for the short-term treatment of insomnia, especially for individuals who have trouble falling asleep. In individuals with chronic insomnia, zolpidem has been shown to help individuals fall asleep faster, reduce nightly awakenings, and improve sleep duration, thus helping several important aspects of sleep. ^{[1] [3]}

Off-Label Uses

Zolpidem may also be used off-label for other sleep-related issues, such as:

• Jet lag

• Long-term treatment of insomnia

Research also shows that zolpidem may help restore brain function in individuals who are in a vegetative state after severe brain injury, so it may be used in these instances as well. ^[1]

Zolpidem Side Effects

There are several possible side effects of zolpidem. The most common zolpidem side effects are: ^[3]

• Drowsiness

• Including next-day drowsiness

• Tiredness

• Dizziness

• Diarrhea

• “Drugged” feeling

• Headache

Other possible side effects of zolpidem include: ^{[2] [3] [4]}

• Dry mouth

• Bodily pain (e.g. back pain, chest pain, stomach pain)

• Palpitations

• Lethargy

• Lightheadedness

• Depression

• Abnormal dreams

• Amnesia

• Nausea

• Constipation

• Rash

• Flu-like symptoms

• Allergies

• Heartburn

• Changes in appetite

• Difficulty with walking or balance

• Shaking

• Muscle aches or cramps

• Ringing in the ears

• Gas

This list may not contain all possible side effects. Reach out to your doctor as soon as possible if you experience these or any other side effects after taking zolpidem.

Rare and Severe Side Effects

There are several rare side effects of zolpidem as well, some of which may be severe or even life-threatening. This includes: ^{[1] [2] [3] [4]}

• Anaphylaxis: Some individuals may have severe allergic reactions (anaphylaxis), which may involve the following symptoms:

• Shortness of breath

• Swelling of the tongue, eyes, throat, lips, or face

• Difficulty breathing or swallowing

• Nausea and/or vomiting

• Rash, hives, and/or itching

• Abnormal changes in thoughts and/or behaviors: This may include:

• Agitation

• Depersonalization

• Hallucinations

• Aggressiveness

• New or worsening depression

• Suicidal thoughts or behaviors

• Unusually outgoing/extroverted behavior

• Memory problems

• Difficulty concentrating

• Confusion

• Central nervous system (CNS) depression: This involves a significant slowing down of CNS activity, which can lead to:

• Severe drowsiness and sedation

• Dizziness

• Slowed or shallow breathing

• Coma or death (in severe instances)

• Tonge, larynx, or glottis swelling (as angioedema)

Some people taking zolpidem may also experience complex sleep behaviors, which are abnormal and potentially dangerous behaviors during sleep, such as walking, talking on the phone, driving, having sex, or making and eating food. Individuals do not recall doing any of these activities the following day. ^{[2] [3]}

Contact your doctor immediately if you notice any of these more severe side effects.

Is it Addictive?

Zolpidem has the potential to be addictive. It is classified as a Schedule IV controlled substance in the Drug Enforcement Administration’s (DEA’s) Controlled Substances Act, due to its potential for abuse and addiction. ^[3]

Some research indicates that zolpidem may have a similar abuse potential as benzodiazepines, such as diazepam. This is in large part due to zolpidem’s sedative properties, which individuals may find pleasurable and, thus, reinforce drug usage. ^[3]

Zolpidem Dosage

The most common dosage recommendations for insomnia in adults are as follows: ^[3]

• Men: 5 to 10 mg per night, immediately before bed

• Women: 5 mg per night, immediately before bed

• Older adults (both men and women): 5 mg per night, immediately before bed

The maximum dose is typically 10 mg per night, although some individuals taking extended-release forms may take up to 12.5 mg per night.

When taking zolpidem, it’s important to slot at least 7 to 8 hours before your planned awakening time. Zolpidem should be taken at the lowest possible dose to achieve the desired effects, and treatment duration should last as short as possible in order to minimize the development of dependence. ^{[1] [3]}

Methods of Administration

Zolpidem is available as oral tablets (Ambien®), oral capsules (Ambien®), extended-release oral tablets (Ambien® CR), an oral spray (Zolpimist®), and sublingual tablets (Edluar®, Intermezzo®). Listed below are the available strengths for each form:

• Oral tablets:

• 5 mg

• 10 mg

• Oral capsules:

• 7.5 mg

• Extended-release oral tablets:

• 6.25 mg

• 12.5 mg

• Sublingual tablets:

• 1.75 mg

• 3.5 mg

• 5 mg

• 10 mg

• Oral spray:

• 5 mg (one spray)

• 10 mg (two sprays)

Precautions

There are several important precautions to be aware of with zolpidem. Firstly, the following populations require cautious use and careful monitoring when using zolpidem:

• Older adults (65 and older): May have reduced drug clearance abilities and an increased risk of sedation, falls, and injuries. Dose should not exceed 5 mg.

• Pregnant women: Use very cautiously, particularly during the third trimester and labor. May cause respiratory depression and other side effects in infants after birth.

• Breastfeeding women: Use very cautiously, or not at all (if possible).

• Individuals with the following conditions:

• Hepatic (liver impairment): Require a reduced dose

• Depression and other mental health issues: May experience worsening symptoms

• Lung disease or any breathing problems (e.g., asthma, bronchitis, emphysema): May increase the risk of respiratory depression

• Myasthenia gravis

• History of drug abuse: Use with extreme caution

Zolpidem should not be used in any of the following instances: ^{[1] [3]}

• Individuals with a history of complex sleep behaviors

• In children under 18

• Those with a known allergy or hypersensitivity to zolpidem

• Individuals with severe depression or suicidality

Zolpidem may also cause drowsiness, decreased alertness, slower reaction times, and issues with coordination, even the day after you take it. This may make it unsafe to drive, operate machinery, or perform other complex mental or physical tasks, even if you feel fully awake and alert. Do not engage in any of these activities until you know how zolpidem affects you and you receive your doctor’s approval to do so. ^{[2] [3]}

Zolpidem may also cause abnormal changes in behavior and thoughts, including new or worsening depression and suicidal thoughts and/or behaviors. Taking zolpidem along with other drugs or alcohol may increase the risk of these side effects.

Lastly, if symptoms of insomnia do not improve after 7 to 10 days with zolpidem, it’s important to undergo further evaluation to identify other possible causes of sleep issues. ^[3]

Harmful Interactions

Zolpidem interacts with many medications and other substances. Combining zolpidem with other CNS depressants increases the risk of dangerous side effects, such as respiratory depression, severe sedation, confusion, coma, and death. ^{[1] [3]}

Examples of such CNS depressants are:

• Alcohol

• Other Z-drugs (e.g., eszopiclone, zaleplon)

• Benzodiazepines (e.g., alprazolam, lorazepam)

• Opioids (e.g., hydrocodone, oxycodone)

Zolpidem may also have harmful interactions with any of the following: ^{[1] [3] [4] [5]}

• Tricyclic antidepressants (e.g., imipramine)

• Antipsychotics (e.g., chlorpromazine)

• Selective-serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine)

• St. John’s wort

• Valerian

• Antifungals (e.g., ketoconazole)

• Antibiotics (e.g., ciprofloxacin, rifampin)

This list does not contain all possible interactions. Tell your doctor everything you take or have taken in the past, including prescription and over-the-counter medicines, vitamins, herbs, and supplements.

Safe Storage

Store zolpidem tightly closed in the original container it came in, and out of the reach of children. Store it at room temperature, away from excess heat, light, and moisture (e.g., not in the bathroom). If you’re using the zolpidem spray, make sure to store the bottle upright. ^[2]