What are the effects of Zolpidem (generic name for Ambien) on the elderly?

From the Guidelines

Zolpidem should be used with extreme caution in elderly patients, with recommended dosing of 5mg (half the standard adult dose) at bedtime for short-term use only. Elderly individuals experience increased sensitivity to zolpidem's effects due to age-related changes in drug metabolism, decreased hepatic clearance, and altered pharmacodynamics in the central nervous system, as reported in a study published in the Annals of Internal Medicine 1. Side effects are more pronounced and potentially dangerous in this population, including excessive sedation, confusion, impaired coordination, and increased fall risk.

Key Considerations

• Elderly patients taking zolpidem face higher risks of hip fractures, cognitive impairment, and delirium, highlighting the need for careful consideration before prescribing this medication 1.
• Morning drowsiness can be particularly problematic, as drug elimination takes longer in older adults, which may impact their daily activities and increase the risk of accidents.
• Non-pharmacological approaches to insomnia should be tried first, including sleep hygiene practices, cognitive behavioral therapy for insomnia, and addressing underlying medical conditions that may disrupt sleep, as recommended by the American College of Physicians 1.

Pharmacological Treatment

• If zolpidem is prescribed, it should be at the lowest effective dose for the shortest duration possible, with regular reassessment of its continued need and effectiveness, to minimize the risk of adverse effects and dependence.
• The use of zolpidem in elderly patients should be carefully monitored, with regular follow-up appointments to assess the patient's response to treatment and adjust the dosage or discontinue the medication as needed, as suggested by a study published in the Annals of Internal Medicine 1.

Alternative Treatments

• Cognitive behavioral therapy for insomnia (CBT-I) has been shown to be effective in improving sleep outcomes in older adults, with moderate-quality evidence supporting its use, as reported in a study published in the Annals of Internal Medicine 1.
• Other non-pharmacological approaches, such as sleep hygiene practices and addressing underlying medical conditions, should also be considered as first-line treatments for insomnia in elderly patients.

From the FDA Drug Label

A total of 154 patients in U.S. controlled clinical trials and 897 patients in non-U. S. clinical trials who received zolpidem were ≥60 years of age. For a pool of U.S. patients receiving zolpidem at doses of ≤10 mg or placebo, there were three adverse reactions occurring at an incidence of at least 3% for zolpidem and for which the zolpidem incidence was at least twice the placebo incidence (i.e., they could be considered drug related). Adverse EventZolpidemPlacebo Dizziness3%0% Drowsiness5%2% Diarrhea3%1% A total of 30/1,959 (1.5%) non-U.S. patients receiving zolpidem reported falls, including 28/30 (93%) who were ≥70 years of age. Of these 28 patients, 23 (82%) were receiving zolpidem doses >10 mg. A total of 24/1,959 (1.2%) non-U. S. patients receiving zolpidem reported confusion, including 18/24 (75%) who were ≥70 years of age. Of these 18 patients, 14 (78%) were receiving zolpidem doses >10 mg. 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 [see WARNINGS AND PRECAUTIONS (5.2)].

The effects of Zolpidem on the elderly include:

• Dizziness (3% incidence)
• Drowsiness (5% incidence)
• Diarrhea (3% incidence)
• Falls (1.5% incidence, with 93% of cases occurring in patients ≥70 years old)
• Confusion (1.2% incidence, with 75% of cases occurring in patients ≥70 years old) The recommended dose of zolpidem 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 2.

From the Research

Effects of Zolpidem on the Elderly

• Zolpidem has been associated with an increased risk of falls in hospitalized patients, with an odds ratio of 4.28 (P <0.001) when prescribed short-term for insomnia 3.
• The relative risk for hip fractures in patients taking zolpidem was described as 1.92 (95% CI 1.65-2.24; P<0.001), with hip fractures being the most commonly seen 3.
• A case series of 119 inpatients aged 50 or older demonstrated that a majority (80.8%) of adverse drug reactions (ADRs) were central nervous system (CNS)-related, such as confusion, dizziness, and daytime sleepiness 3.
• Zolpidem is considered a reasonable choice of therapy for elderly patients because it has a lower incidence of residual daytime sleepiness and risk of falls when compared to other drugs 3.
• The dose of zolpidem should be adjusted to account for the slower drug metabolism in elderly patients 3, 4.

Pharmacokinetics and Pharmacodynamics in the Elderly

• Clearance of zolpidem in children is 3 times higher than in young adults, and is lower in very elderly people 4.
• Dosage reduction appears to be prudent in patients with renal disease, and caution should be exercised when prescribing zolpidem to elderly patients with hepatic impairment 4.
• Zolpidem pharmacokinetics are unchanged during multiple-dose treatment, and are not significantly influenced by gender 4.

Safety Analysis in Elderly Subjects

• A study investigating the safety of zolpidem administration in extremely old elderly (80 years of age or older) found that low-dose zolpidem can be safely prescribed to subjects without cognitive or mental complications 5.
• The most common adverse symptoms reported were impaired balance and/or falls (1.8%) and morning drowsiness (1.3%) 5.
• Multiple logistic regression analyses showed that subjects 80 years of age or older were at lower risk of adverse symptoms (odds ratio 0.39,95% confidence intervals: 0.17-0.88) 5.

Therapeutic Potential and Adverse Effects

• Zolpidem has a rapid onset of action and short elimination half-life, reducing the latency to and prolonging the duration of sleep in patients with insomnia 6.
• Rebound effects on withdrawal of the drug have not been observed, and its effects on anxiety appear to be minor 6.
• Adverse effects are predominantly CNS and gastrointestinal in nature, and altered pharmacokinetics may lead to an increase in dose-proportionate adverse effects in the elderly and in patients with renal dysfunction 6.