Zolpidem (Oral)

Zolpidem (more popularly known as Ambien) is a sedative drug used to treat patients who suffer from insomnia.

Overview:

Zolpidem is a sedative-hypnotic drug used by patients to combat insomnia. The drug is best known by the brand name Ambien, which is manufactured by Sanofi-Aventis. Generic versions are available. A number of Hollywood actors, including Heath Ledger and Jack Nicholson, have talked publicly about their Ambien use, fueling a perverse culture of abuse around the drug. As a result of this, and of its legitimate potential for abuse (its effects are similar to the benzodiazepine class of drugs), the U.S. government considers Ambien to be a schedule 4 controlled substance.

Zolpidem is most commonly available in 5 mg and 10 mg tablets, to be taken orally.

Conditions treated:

  • Insomnia

Type of medicine:

  • Sedative-hypnotic

The efficacy of zolpidem was studied in several different clinical trials, each reporting positive effects on sleep in the zolpidem group over the placebo group. In two different studies studying zolpidem's effects on transient insomnia, zolpidem treated groups (at three different strength levels) were all superior to the placebo groups in terms of sleep latency, sleep duration, and the number of awakenings. In a study of zolpidem's effects on geriatric patients, zolpidem was superior to the placebo group in sleep latency, sleep efficiency, sleep duration, sleep quality, and the number of awakenings.

When zolpidem was studied on patients who suffered from chronic insomnia, similar results were ascertained. Across two studies, the group given the 10 mg dose of zolpidem reported superiority in sleep latency. In one study, zolpidem was comparable to the placebo in sleep efficiency for two of the weeks. For the other study, zolpidem was superior to the placebo in terms of sleep efficiency across all four weeks.

Side effects:

Zolpidem is a powerful drug with a long list of side effects. Many of zolpidem's side effects do not require medical attention and may diminish as treatment goes on. Other, rarer side effects can be serious and sometimes lethal. Patients should consult with their doctor about how zolpidem affects them.

Zolpidem binds to receptors which slow brain activity. Patients should expect to feel drowsy, sluggish, or dull while under the effects of zolpidem. Although zolpidem is only recommended to be taken at night, it has been known to have effects the following day, which can include:

  • Drowsiness
  • Motor impairment
  • Lack of focus

These side effects can be exacerbated by a lack of sleep the night before. Patients are encouraged to get a full seven to eight hours of sleep on the nights they take zolpidem to decrease the risk of day-after effects.

Common side effects can include:

  • Drowsiness
  • Headache
  • Muscle aches
  • Stuffy or runny nose
  • Chest pain
  • Less common side effects can include:
  • Abdominal pain
  • Stomach discomfort
  • Back pain
  • Belching
  • Abnormal forgetfulness
  • Memory loss
  • Body aches
  • Congestion
  • Diarrhea
  • Constipation
  • Difficulty moving
  • A constant sensation of movement, rushing
  • Double vision
  • Heartburn
  • Hoarseness
  • Indigestion
  • Abnormally long or heavy menstruation
  • Nausea
  • Stiffness and muscle pain
  • Tenderness in the face
  • Spinning sensation
  • Swollen or painful lymph nodes
  • Voice changes
  • Changes in manner of speaking
  • Unpleasant mouth taste
  • Changes in taste
  • Breast pain
  • Sweating
  • Itchy genitals
  • Pain during sexual intercourse
  • Slurred speech
  • Pale skin
  • Vaginal discharge
  • Vomiting
  • Difficulty waking up
  • Anxiety
  • Bladder pain
  • Bloody or discolored urine
  • Burning, crawling, or ‘pins and needles' sensations
  • Chills
  • Cold sweats
  • Crying
  • Lowered awareness/responsiveness
  • Depersonalization
  • Dysphoria
  • Euphoria
  • Fainting
  • Paranoia
  • Heightened emotions
  • Irritability
  • Shaking in the arms and legs
  • Shortness of breath
  • Hyperventilation
  • Irregular heartbeat
  • In rare cases, zolpidem's side effects may include:
  • Skin blemishes
  • Blindness
  • Blurred vision
  • Changes in vision
  • Lowered sex drive
  • Eye pain
  • Difficulty focusing in the eyes (like a camera)
  • Rogue feelings of warmth
  • Erectile dysfunction
  • Irregular bowel movements
  • Increased appetite
  • Sensitivity to light
  • Severe sunburns
  • Pimples
  • Red or discolored skin
  • Tearing
  • Weight loss
  • Ulcers
  • Delusions
  • Dementia
  • Apathy
  • Lack of emotion
  • Clumsiness

There is evidence that negative side effects increase as the dose goes up. Patients taking a higher dose of zolpidem may be at a higher risk for more severe side effects, and patients taking a lower dose may be at less risk.

Zolpidem is a powerful psychoactive drug, and as such can have a serious impact on a patient's mental state. Patients who experience any of the following should contact their doctor immediately:

  • Acute memory loss
  • Behavioral changes
  • New or worsening depression
  • Suicidal thoughts or actions
  • Hallucinations
  • Anxiety
  • Unusual feelings of aggression
  • Confusion
  • Agitation

In clinical trials, as many as 7% of the group taking zolpidem experienced hallucinations during the night, compared with 0% in the control group.

In rare cases, patients have been observed engaging in waking activities while asleep while they were on zolpidem. Patients have sleepwalked, driven while asleep, prepared and consumed food while asleep, and made phone calls while asleep. In the majority of cases, patients do not remember participating in their sleeping activities.

These symptoms can be a threat to the patient and to others. Patients should contact their doctor immediately if they begin to notice signs that they are active while sleeping. Alcohol or other sedative medications can increase the risk of unwanted nighttime activity.

Allergic reactions to zolpidem are rare but possible. Patients should contact their doctor immediately if they experience the symptoms of serious allergic reaction, including rash, hives, itching/swelling of the face, dizziness, anaphylaxis, or difficulty breathing.

It is important to remember that zolpidem is a medication that is designed to help the patient. Patients who experience multiple side effects, or severe side effects should consult their doctor on whether or not zolpidem is worth taking.

Zolpidem is not as addictive as other drugs like it that are prescribed to treat insomnia, but dependence can occur. As a result of long-term use or extreme doses, withdrawal symptoms can occur. Withdrawal symptoms can include:

  • Agitation
  • Sweating
  • Shakiness
  • Stomach cramps
  • Fever
  • High blood pressure
  • Nausea
  • Depression
  • Panic attacks
  • Insomnia
  • Seizures
  • Convulsions

In instances of zolpidem dependence, patients can experience rebound insomnia, when taking zolpidem one night will cause insomnia the next. Rebound insomnia can last as long as several weeks. Patients who have endured rebound insomnia have reported better sleep after coming off the drug.

This is not necessarily a complete list of side effects. Patients can report side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

Dosage:

Zolpidem is available in the form of 5 mg and 10 mg tablets, and 6.25 mg extended release tablets.

In its standard form female patients are recommended to take 5 mg of zolpidem once before bed, and male patients are recommended to take 5 mg - 10 mg once before bed on an empty stomach.

In extended release form, female patients are recommended to take 6.25 mg of zolpidem once before bed, and male patients are recommended to take 12.5 mg of zolpidem once before bed on an empty stomach.

Older adults who are taking zolpidem are usually recommended to stick with either 5 mg of zolpidem or 6.25 mg of zolpidem once before bed, regardless of gender.

Zolpidem is flushed out of the male body more quickly, hence the discrepancy between the two genders' recommended dosage.

Dosage adjustments are usually recommended for the following conditions:

  • Mild hepatic impairment: 5 mg dose (all genders)
  • Debilitated patient: 5 mg dose (all genders)

Patients planning to take zolpidem concurrently with a CNS depressant: there is no standard adjustment recommended, although patients are encouraged to exercise caution and consult with their doctors before taking zolpidem.

Patients with a history of benzodiazepine or those who have built up a tolerance to benzodiazepines may require a strong dose of zolpidem to properly treat insomnia.

Patients with zolpidem extended release tablets should swallow the pill whole. Chewing or crushing the pill will defeat the purpose of the extended release, and cause the patient to take a higher dose than they would have otherwise intended.

Zolpidem is fast acting. Patients should only take zolpidem when they are ready to fall asleep.

If a patient misses a dose of zolpidem, they should return to their normal dosing schedule. Under no circumstances should a patient double up on their dose to make up for missed doses.

Interactions:

Zolpidem can react with a long list of different medications and conditions. Zolpidem is most reactive with any kind of sedative agent, painkiller, or depressant.

Zolpidem is a powerful anti-insomnia drug. Combining zolpidem with any other sleeping medication or anti-anxiety drug (such as benzodiazepines) will amplify the effects of zolpidem, making serious side effects like memory loss, sleepwalking, and coma more likely.

Taking painkillers, such as any opiate, drinking alcohol or consuming a cough medication while on zolpidem can put the patient at serious risk of adverse side effects. Acute respiratory depression, coma, and even death have resulted from mixing zolpidem with any of the aforementioned drugs.

While zolpidem itself will not cause respiratory depression (unlike a number of other GABA agonists), combining zolpidem with any medication or condition which heightens the effects of zolpidem will put the patient at risk of respiratory depression.

Taking allergy medication, cold medication, or other antihistamines will usually have a mild intensifying effect, putting the patient at greater risk for less serious side effects, such as dizziness, confusion, and altered motor control. It is especially inadvisable to combine zolpidem with the nighttime versions of various allergy and cold medicines. The alcohol and other sleeping agents can react powerfully with zolpidem.

Zolpidem can interact with some antibiotic and HIV medications. The interaction between the two drugs can lead to mild upticks in side effects or diminishing effects from the drugs.

Zolpidem is sometimes taken to counteract the effects of stimulants such as methamphetamine or cocaine. Zolpidem does not interact chemically with stimulants, but the two have diametrically opposed effects - stimulating and sedating. While zolpidem might mute the stimulating effect of a stimulant, it won't change the load stimulants put on the body. Similarly, stimulants can mute the sedative effects of zolpidem, but do nothing to change the load zolpidem puts on the body.

During clinical trials, several patients who were taking SSRIs (selective serotonin reuptake inhibitors) dropped out of the trials due to adverse behavioral effects. The patients who dropped out reported experiencing:

  • Impaired focus
  • New or aggravated depression
  • Manic reactions
  • Suicidal ideations.

In one case, a patient had to be removed from the trial due to a suicide attempt.

When zolpidem is taken concurrently with the drug fluoxetine (an SSRI) it was observed to increase zolpidem's half-life by 17%. Because of this (and the fact that fluoxetine is an SSRI), patients should exercise extreme caution when considering taking zolpidem.

Patients taking sertraline (Zoloft, an SSRI) during clinical trials showed an increase in the concentrations of zolpidem in the patient's body. Patients who are taking sertraline should exercise caution when considering taking zolpidem.

Patients should consult their doctor when considering taking zolpidem when they are taking fluoxetine, sertraline, or any other SSRI.

The following drugs interact seriously with zolpidem. They are predominantly, but not entirely, sedatives, depressants, or pain relievers.

  • Codeine
  • Butalbital
  • Propoxyphene
  • Hydrocodone
  • Phenylephrine
  • Tramadol
  • Alfentanil
  • Dihydrocodeine
  • Anhydrous calcium iodide
  • Aspirin
  • Pentazocine
  • Oxycodone
  • Guafenesin
  • Bromodiphenhydramine
  • Brompheniramine
  • Phenylpropanolamine
  • Pseudoephedrine
  • Bupivacaine
  • Fentanyl
  • Hydromorphone
  • Sufentanil
  • Buprenorphine
  • Naloxone
  • Butorphanol
  • Carbinoxamine
  • Chlorcyclizine
  • Chlorpheniramine
  • Dexbrompheniramine
  • Dezocine
  • Droperidol
  • Homatropine
  • Hydromorphone
  • Ibuprofen
  • Levomethadyl acetate
  • Levorphanol
  • Meperidine
  • Morphine
  • Methadone
  • Nalbuphine
  • Naltrexone
  • Remifentanil
  • Sodium oxybate
  • Tapentadol

This is not a complete risk of drug interactions. Patients should consult with their doctor about possible interactions with any and all drugs or supplements they take before considering zolpidem.

As far as supplements go, melatonin, a sleep aid, has the potential to react negatively with zolpidem.

Warnings:

Zolpidem is considered a class C drug for pregnancy risk, meaning risk cannot be ruled out in humans. In trials done on animals, zolpidem was shown to have an adverse effect on the fetus. Patients who are pregnant or may become pregnant should consult with their doctor before taking zolpidem.

Long-term zolpidem use can cause zolpidem dependency. Patients taking zolpidem should try to use the drug sparingly. Zolpidem is considered a class 4 scheduled substance.

Patients should avoid eating for several hours before they plan to take zolpidem. Having food in the stomach will delay the onset of zolpidem, diminishing its effectiveness.

In geriatric patients, when supplied with a dose above the recommended 5 mg dose, there was evidence of rebound insomnia and mild sleep impairment during the first week of the trial. However, there was no evidence of this in patients who took the correct 5 mg dose. Geriatric patients should take special care to stick to the doses prescribed to them.

Zolpidem has been known to have day-after effects on patients who take zolpidem to combat insomnia. Patients who get less than seven or eight hours' sleep after taking zolpidem, or who are taking doses of zolpidem that are greater than necessary, are at higher risk of this. Day-after effects of zolpidem can include:

  • Daytime drowsiness
  • Nausea
  • Dizziness
  • Headaches
  • Vomiting

Patients should avoid consuming alcohol while taking zolpidem. Alcohol can amplify the effects zolpidem has on the central nervous system, increasing the likelihood of side effects such as balance loss, confusion, and drowsiness. Alcohol has also been tied to episodes of sleepwalking in zolpidem patients.

Patients who are intoxicated should avoid taking zolpidem, as a mixture of the two can result in acute respiratory depression or even death.

Patients who were given 10 mg and 20 mg doses of zolpidem (20 mg being well above the daily prescribed limit) reported a considerable decrease in next morning recall of events that occurred while zolpidem was at its peak effect. Subjective evidence also existed for anterograde amnesia occurring on the nights some patients took zolpidem.

Patients with depression should exercise caution when considering taking zolpidem (or any other anxiolytic, sedative, or hypnotic drug). Zolpidem can cause a variety of different behavioral or thought process changes in depressed patients, including:

  • Decreased inhibition
  • Aggressiveness
  • Agitation
  • Hallucinations

Zolpidem has also been tied to an increased likelihood of suicidal thoughts and/or actions in depressed patients. Patients with a history of depression (or any other medical illness) should consult with a doctor before taking zolpidem.

Persons with a history of drug addiction, particularly to other anxiolytic, sedative or hypnotic drugs should exercise caution when considering taking zolpidem. Patients with a history of addiction to alprazolam (Xanax), lorazepam (Ativan), diazepam (Valium), or any other benzodiazepine should be especially cautious, as zolpidem effects are similar to that of a benzodiazepine. Zolpidem is not as addictive as a normal benzodiazepine, but can cause dependence, especially when abused. Patients who have abused zolpidem or become dependent on it may experience withdrawal symptoms if they abruptly stop taking zolpidem.

Zolpidem is primarily metabolized in the liver. Patients with hepatic impairment have shown increased concentrations of zolpidem in the plasma. As a result, patients with hepatic impairment should exercise caution when considering taking zolpidem. Patients with acute hepatic impairment should not take zolpidem.

Zolpidem can have an anticholinergic effect. As a result, it can cause complications in patients with glaucoma. Patients with glaucoma should consult their doctor before taking zolpidem.

Patients with hepatic impairment should exercise caution when considering taking zolpidem. Zolpidem is metabolized in the liver, and the half life of zolpidem can be prolonged in patients with hepatic impairment. Patients with mild to moderate hepatic impairment should consult with their doctor before taking zolpidem. Patients with severe hepatic impairment should avoid taking zolpidem.

Patients with any form of respiratory depression (including apnea, asphyxia, pulmonary impairment) should exercise caution when considering taking zolpidem, since zolpidem may exacerbate their condition.

There is insufficient data to determine the effects of renal dysfunction of patients taking zolpidem. As a result, patients with renal dysfunction may need to be monitored for signs of buildup while taking zolpidem. Patients with renal dysfunction should consult with their doctor before taking zolpidem.

Additionally, patients with myasthenia gravis (a muscular disease) should consult with their doctor before taking zolpidem. Zolpidem has been known to aggravate symptoms of myasthenia gravis.

Insomnia can be a sign of other, underlying problems. By treating insomnia with zolpidem, the patient runs the risk of simply covering up those problems rather than dealing with them. If insomnia does not remit after 1 to 2 weeks of zolpidem use, the patient should consult with their doctor about the possibility of underlying problems.

Storage:

Zolpidem should be stored at a room temperature of 68 to 75 degrees Fahrenheit.

Because of the potential risk zolpidem poses to children, zolpidem should be stored out of reach of children.

Summary:

Zolpidem selectively binds with the GABA - BZ receptor in the brain (for comparison, benzodiazepines and alcohol also act on the GABA receptors in the brain) to produce its calming and sedative effects. The result is one of the most potent sleep aids commercially available. Because zolpidem is so potent, patients should have a healthy respect for the drug. The standard doses of zolpidem are just below the dose of zolpidem necessary to produce respiratory depression in most patients. Patients should be careful not to do or take anything to amplify the effects of zolpidem, lest they put themselves over the edge and at risk for respiratory depression (a potentially lethal condition that can cause a patient to die in his or her sleep).

Patients should weigh the risks and benefits of taking zolpidem very carefully. Physical, mental, behavioral, and emotional side effects are all a very real possibility, but the payoff (finally being able to sleep) can be huge. Regardless of their circumstances, any patient who chooses to take zolpidem should be aware at all times that they are taking a psychoactive drug, and that any unusual or rogue thoughts, feelings, or sensations could all be attributed to the zolpidem they are taking. With the severity of potential side effects, vigilance is paramount. Patients taking zolpidem should be able to consult with their doctor at any time about any new or worsening side effects they are experiencing.

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Last Reviewed:
December 23, 2017
Last Updated:
April 04, 2018
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