Zolpidem for insomnia and sleep disorders: How well it works? How safe is Zolpidem?
Zolpidem is available under different brand names, including:
- Ambien and Ambien CR (Sanofi Aventis)
- Nocte and Nocte Sublingual
- Stilnox and Stilnox CR
How does Zolpidem help people with Insomnia?
Zolpidem (Ambien) improves sleep quality by helping you:
- To sleep earlier: It reduces sleep latency (the time you fall asleep after going to bed)
- To sleep longer: It increases the total sleep time
- To wake less frequently during sleep: It reduces the number of times you wake up during sleep.
For these reasons, the FDA has approved Zolpidem for the following sleep-related medical problems:
- Short-term treatment of insomnia especially those who have difficulty falling asleep.
Zolpidem has been found to be effective for up to 5 weeks.
Other therapeutic benefits of Zolpidem (Ambien) include:
- It relaxes your msucles
- It may help people recover from a vegetative state if the brain injury is not severe and does not involve the brainstem [Ref]
A night of adequate and good-quality sleep has multiple short-term and long-term health benefits. Thus, Zolpidem not only improves sleep but has indirect effects on our heart, brain, and other organs as well.
The short-term and long-term health-related effects of poor sleep are summarized in this table [Ref]:
Short-term effects of Insomnia
Long-term effects of Insomnia
|Day-time sleepiness||Cardiac morbidity|
|Fatigue and exhaustion||Ischemic stroke|
|Absence from work||Diabetes|
|Impaired ability to perform tasks||Glucose intolerance|
|Nodding off during daily activities||Weight gain|
|Poor concentration||Impaired psychomotor functioning|
|Limited enjoyment of family and social life||Impaired performance, memory, and alertness|
Zolpidem Dose for Insomnia:
Zolpidem is available in 5 mg and 10 mg tablets. It is also available as an oral spray and a sublingual formulation which gets readily absorbed.
The usual and maximum dose is 10 mg before going to bed.
However, the dose is reduced in older individuals and those who are on other medications that depress the central nervous system including alcohol.
The dose should also be reduced in individuals who have liver dysfunction.
|Usual Dose||10 mg at bedtime|
|Maximum Dose||10 mg at bedtime|
|Older individuals and those on other CNS depressants||5 mg at bedtime|
Zolpidem Mechanism of Action:
Zolpidem is a non-benzodiazepine hypnotic drug. It binds to and activates GABA-A receptors in the brain which induces sleep.
However, unlike Benzodiazepines, Zolpidem specifically binds to the alpha-1 and alpha-5 subunits of BZ-1 receptors.
In simple words, Benzodiazepines are non-specific activators of GABA receptors while Zolpidem acts on specific receptors in the brain.
Because of its specificity, it does not have anti-seizure activity. It does not cause significant muscle relaxation and is less likely than benzodiazepines to make you feel sleepy in the morning.
Zolpidem is readily absorbed from the intestines. It has a rapid onset of action and a very short half-life. Its mean half-life is only 2.8 hours.
Because of its short half-life, it is not associated with daytime somnolence and people feel more alert compared to other drugs.
It is metabolized by CYP3A4 and excreted via the kidneys.
How Effective is Zolpidem for Insomnia?
Zolpidem (Ambien) is considered superior to all the Z-drugs. Non-benzodiazepine hypnotic drugs are commonly referred to by physicians as Z-drugs [Ref].
Because of its superior efficacy, it is the usual first choice for treating insomnia among the Z-drugs.
The other three drugs included in the Z-drugs category include:
Zaleplon (Sonata – Pfizer) is a short-acting drug and is preferred to be used upon sleep awakening at night. It may not be a good choice for sleep maintenance compared to Zolpidem.
Eszopiclone (Lunesta) is a relatively longer act than Zolpidem (Ambien) and is associated with next-day morning drowsiness.
Efficacy of Zolpidem for Insomnia [Ref]:
The effectiveness of Zolpidem for insomnia has been studied in multiple randomized clinical trials.
A meta-analysis that included 6 randomized controlled clinical trials involving more than 1000 patients concluded:
- Zolpidem improved TST (total sleep time)
- It improved sleep quality, and
- Reduced sleep latency
However, Zolpidem did not improve WASO (wakefulness after sleep onset). In addition, the drug was associated with minimal side effects including the elderly patients.
Zolpidem for Insomnia Vs Temazepam [Ref]:
Zolpidem was compared with Temazepam in a study for the treatment of transient insomnia.
Zolpidem showed superior subjective hypnotic efficacy, reduced awakenings, and WASO (wake after sleep onset), and impaired DSST performance, while temazepam did not significantly reduce awakenings or DSST (digital symbol substitution test) performance.
Zolpidem 10 mg
Temazepam 15 mg
|Objective Sleep Latency||No significant reduction||No significant reduction|
|Awakenings||Reduced||Did not reduce|
|Wake After Sleep Onset (WASO)||Reduced||Did not reduce|
Other uses of Zolpidem:
Zolpidem has been studied in patients with sleep issues who have concomitant PTSD (post-traumatic stress disorder). It improves insomnia associated with PTSD [Ref]
Zolpidem and Melatonin have also been studied for treating Jet Lag. Jet lag severity was markedly reduced by Zolpidem compared to Melatonin [Ref]
Insomnia and Depression:
Zolpidem (Ambien) is not a good choice for people with insomnia and concomitant depression.
However, in patients treated with fluoxetine or sertraline, adding Zolpidem did not have any significant drug interactions and was considered safe and effective [Ref].
In another study, Zolpidem was given to patients who were on escitalopram for depression. Zolpidem improved sleep quality, reduced sleep latency, reduced WASO (wake after sleep onset), and TST (total sleep time) [Ref]
Doxepin (Sinequan) is an antihistamine that has been proven to reduce the time to sleep after going to bed, increase total sleep time, and reduce frequent awakenings after sleep onset.
Mirtazapine (Remeron) and Trazodone (Desyrel) are antidepressants that are preferred over Ambien for treating depression and concomitant insomnia.
Mirtazapine is preferred over Trazodone for insomnia because of the increased risk of cardiac conduction abnormalities.
Zolpidem Side Effects:
Zolpidem for insomnia, even for short-term insomnia, is associated with an increased risk of falls and fractures in aged people.
It is also associated with reduced short-term memory, impaired attentiveness, confusion, dizziness, and daytime drowsiness.
Zolpidem use is also associated with abnormal sleep behaviors including sleep paralysis, hallucinations, sleep driving, sleep walking, and committing crimes during sleep.
Although Zolpidem and other Z-drugs are less likely to cause withdrawal effects, dependence, and rebound insomnia compared to Benzodiazepines, reports of misuse, dependence, and withdrawal including seizures have all been reported.
Lastly, women are more sensitive to the Z-drugs. These drugs should be started at a very low dose in women and the dose gradually titrated up to the maximum dose of 10 mg.
Some of the common side effects are summarized in the table below:
Zolpidem is an effective medicine for sleep induction. It reduces sleep latency, improves sleep quality, and is less likely to be associated with significant adverse events.