What are the long-term risks of zolpidem (sedative-hypnotic) use in elderly patients?

From the Guidelines

Elderly patients should avoid long-term zolpidem use due to significant risks that outweigh its benefits, with treatment limited to short courses (7-10 days) at reduced dosages (5mg immediate-release or 6.25mg extended-release) 1.

Risks Associated with Zolpidem Use

The most concerning risks include:

• Increased falls and fractures
• Cognitive impairment
• Delirium
• Development of dependence or addiction Elderly patients are particularly vulnerable to these effects due to age-related changes in drug metabolism, decreased drug clearance, and existing cognitive vulnerability 1.

Adverse Effects of Zolpidem

Zolpidem can cause:

• Daytime sedation
• Impaired balance
• Memory problems that persist beyond the intended sleep period Long-term use may also lead to tolerance, requiring higher doses for the same effect, and withdrawal symptoms upon discontinuation 1.

Non-Pharmacological Approaches

Non-pharmacological approaches to insomnia, such as sleep hygiene improvements and cognitive behavioral therapy, should be tried first 1.

Medication Management

If medication is necessary, elderly patients should be regularly reassessed for continued need, effectiveness, and adverse effects 1.

Key Considerations

• Zolpidem can worsen respiratory conditions and interact with other medications commonly taken by elderly patients
• The FDA recommends dosages lower than those used in many studies, especially for older adults 1
• Evidence is insufficient to evaluate the balance of the benefits and harms of long-term use of pharmacologic treatments in adults with chronic insomnia disorder 1

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 long-term risks of zolpidem use in elderly patients include:

• Increased risk of falls: 1.5% of non-U.S. patients reported falls, with 93% of these patients being ≥70 years of age.
• Confusion: 1.2% of non-U.S. patients reported confusion, with 75% of these patients being ≥70 years of age.
• Dizziness: 3% of U.S. patients reported dizziness.
• Drowsiness: 5% of U.S. patients reported drowsiness. 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 2.

From the Research

Long-term Risks of Zolpidem Use in Elderly Patients

• The use of zolpidem in elderly patients has been associated with several risks, including cognitive and balance dysfunctions, as well as an increased risk of Alzheimer's disease 3, 4.
• A study published in 2016 found that low-dose zolpidem can be safely prescribed to elderly patients without cognitive or mental complications, with a lower risk of adverse symptoms in patients 80 years of age or older 5.
• Another study published in 2020 found that zolpidem is effective in reducing sleep latency and episodes of wake after sleep onset, and increasing total sleep time and sleep efficiency in elderly patients, but noted that few retrospective studies associate zolpidem use with risk of falls, fractures, dementia, cancer, and stroke 6.
• A study published in 2004 found that zolpidem is effective and well-tolerated in elderly patients with sleep disorders and comorbidities, including diabetes and arterial hypertension 7.
• However, a study published in 2021 found that zolpidem, even in usual doses, increases the risk of balance dysfunctions in elderly patients, although it does not appear to affect cognitive changes 3.
• A retrospective cohort study published in 2017 found that high cumulative doses of zolpidem (>180 cDDD) are associated with an increased risk of Alzheimer's disease in older people, suggesting that caution should be exercised when considering long-term use of zolpidem in older patients 4.

Specific Risks Associated with Zolpidem Use

• Cognitive dysfunctions: no statistically significant difference between zolpidem and placebo 3.
• Balance dysfunctions: statistically significant difference between zolpidem and placebo, with zolpidem increasing the risk of balance dysfunctions 3.
• Alzheimer's disease: high cumulative doses of zolpidem (>180 cDDD) associated with an increased risk of Alzheimer's disease 4.
• Falls, fractures, dementia, cancer, and stroke: few retrospective studies associate zolpidem use with these risks, but the evidence is limited 6.