What are the considerations for zolpidem (Ambien) use?

From the Guidelines

Ambien (zolpidem) should be used with caution and only for short-term treatment of insomnia, ideally 7-10 days, due to the risk of dependence, tolerance, and serious adverse effects. When considering Ambien, it's essential to weigh the benefits against the potential harms, as evidenced by low- to moderate-quality evidence showing improvements in sleep outcomes, such as sleep onset latency, total sleep time, and wake after sleep onset 1. The typical starting dose is 5mg for women and older adults or 5-10mg for men, taken right before bedtime when you have 7-8 hours available for sleep. Some key considerations for Ambien use include:

• Taking it on an empty stomach for faster effect
• Avoiding alcohol, which can cause dangerous respiratory depression
• Not driving or performing activities requiring alertness after taking it
• Being aware of potential side effects, such as morning drowsiness, headache, dizziness, and rarely, complex sleep behaviors like sleepwalking or sleep-driving
• Discussing with your doctor if you have respiratory conditions, history of substance abuse, depression, or are taking other medications, as these factors may affect whether Ambien is appropriate for you. According to the FDA, dosages should be lower than those used in many studies, especially for older adults, and patients should not continue using the drugs for extended periods 1. Additionally, a systematic review found that nonbenzodiazepine BZRAs, including zolpidem, improved sleep efficiency and other sleep outcomes compared with placebo, but the benefits seemed to outweigh potential harms only when administered at the lowest effective dose and for the shortest possible duration 1.

From the FDA Drug Label

Zolpidem tartrate tablets are indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation. The clinical trials performed in support of efficacy were 4 to 5 weeks in duration with the final formal assessments of sleep latency performed at the end of treatment. Zolpidem crosses the placenta and may produce respiratory depression and sedation in neonates Monitor neonates exposed to zolpidem tartrate during pregnancy and labor for signs of excess sedation, hypotonia, and respiratory depression and manage accordingly. The dose of zolpidem tartrate in elderly patients is 5 mg to minimize adverse effects related to impaired motor and/or cognitive performance and unusual sensitivity to sedative/hypnotic drugs Women clear zolpidem tartrate from the body at a lower rate than men. Cmax and AUC parameters of zolpidem were approximately 45% higher at the same dose in female subjects compared with male subjects Given the higher blood levels of zolpidem tartrate in women compared to men at a given dose, the recommended initial dose of zolpidem tartrate for adult women is 5 mg, and the recommended dose for adult men is 5 or 10 mg. Concomitant use of zolpidem with other CNS depressants increases the risk of CNS depression.

Key Considerations for Ambien (Zolpidem):

• Pregnancy and Lactation: Zolpidem may produce respiratory depression and sedation in neonates, and its use during pregnancy and lactation should be carefully monitored.
• Dosing: The recommended dose for adult women is 5 mg, and for adult men is 5 or 10 mg. In geriatric patients, the dose is 5 mg regardless of gender.
• Drug Interactions: Concomitant use with other CNS depressants, such as alcohol, increases the risk of CNS depression.
• Special Populations: Zolpidem is not recommended for use in children, and its use in patients with hepatic impairment should be avoided.
• Gender Differences: Women clear zolpidem at a lower rate than men, resulting in higher blood levels at the same dose.
• Elderly Patients: The dose of zolpidem in elderly patients should be minimized to 5 mg to reduce adverse effects related to impaired motor and/or cognitive performance. 2 2 2

From the Research

Considerations for Ambien

• Ambien, also known as zolpidem, is a nonbenzodiazepine hypnotic indicated for the short-term treatment of insomnia 3.
• It improves sleep in patients with insomnia and has a low propensity to cause clinical residual effects, withdrawal, dependence, or tolerance 3.
• The use of zolpidem in an 'as-needed' regimen has been shown to produce a global improvement in sleep 3.
• However, zolpidem has been associated with some risk for dependence and abuse, particularly in former substance abusers and psychiatric patients 4.
• Common adverse events associated with zolpidem include unpleasant taste, dry mouth, somnolence, and dizziness 5.
• Zolpidem has also been linked to rare but serious adverse events, such as anaphylaxis, angio-oedema, and complex sleep-related behaviors, including sleep-driving 4.

Comparison with Other Hypnotics

• Zolpidem has been compared to other hypnotics, such as eszopiclone and zopiclone, in terms of efficacy and safety 4, 5, 6.
• Eszopiclone has been shown to be effective in improving sleep onset and maintenance, with minimal risk of harm when taken as recommended 5.
• Zopiclone has also been found to be effective in improving sleep quality, but its safety in cognition remains to be verified 6.
• Orexin dual receptor antagonists (DORAs) have been recommended as the best intervention for insomnia due to their high efficacy in inducing and maintaining sleep without impairing cognition 6.

Switching or Deprescribing Hypnotic Medications

• Guidelines have been developed to inform clinicians on the safest and most effective way to transition from one insomnia medication to another or deprescribe altogether 7.
• When switching or discontinuing insomnia medications, it is recommended to taper benzodiazepine hypnotic drugs and provide additional cognitive behavioral therapy for insomnia (CBT-I) 7.
• For Z-drugs like zolpidem and eszopiclone, tapering is recommended, especially when prescribed at supratherapeutic doses, with a 1-2 day delay in administration of the next insomnia therapy when applicable 7.