Why not use zolpidem (Ambien) for this patient?

From the Guidelines

Zolpidem (Ambien) should be avoided in this patient due to significant safety concerns. Zolpidem is a sedative-hypnotic medication that carries risks of dependence, tolerance, rebound insomnia, and adverse effects including confusion, amnesia, and complex sleep behaviors like sleep-walking or sleep-driving, as reported in a study published in 2024 1. It's particularly problematic for elderly patients who experience increased sensitivity to its effects and have higher risks of falls, cognitive impairment, and drug interactions. The medication is intended only for short-term use (7-10 days) as effectiveness diminishes with continued use while risks accumulate.

Some of the key concerns with zolpidem include:

• Risk of cognitive impairment and increased fall risk, especially in elderly patients
• Potential for dependence and tolerance
• Adverse effects such as confusion, amnesia, and complex sleep behaviors
• Limited efficacy for long-term use, with most benefits seen in short-term treatment

For this patient, safer alternatives should be considered, such as:

• Addressing underlying causes of insomnia through sleep hygiene practices
• Cognitive behavioral therapy for insomnia (CBT-I)
• If medication is necessary, options with better safety profiles like low-dose trazodone, doxepin, or melatonin, as suggested by a study published in 2020 1. These alternatives provide better long-term management without the significant risks associated with zolpidem use. According to a study published in 2016 1, the American College of Physicians recommends that clinicians should use cognitive behavioral therapy for insomnia (CBT-I) as the first-line treatment for chronic insomnia disorder in adults, and that the use of zolpidem should be limited to short-term treatment due to its potential risks and side effects.

From the FDA Drug Label

Some patients have required medical therapy in the emergency department. If angioedema involves the throat, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with zolpidem should not be rechallenged with the drug. Abnormal thinking and behavior changes have been reported in patients treated with sedative/hypnotics, including zolpidem tartrate. In primarily depressed patients treated with sedative-hypnotics, worsening of depression, and suicidal thoughts and actions (including completed suicides), have been reported. Although studies with 10 mg zolpidem tartrate did not reveal respiratory depressant effects at hypnotic doses in healthy subjects or in patients with mild to moderate chronic obstructive pulmonary disease (COPD), a reduction in the Total Arousal Index, together with a reduction in lowest oxygen saturation and increase in the times of oxygen desaturation below 80% and 90%, was observed in patients with mild to moderate sleep apnea when treated with zolpidem compared to placebo.

Zolpidem may not be suitable for this patient due to the following key concerns:

• Angioedema: Zolpidem can cause angioedema, which can be fatal if it involves the throat, glottis, or larynx.
• Abnormal thinking and behavior changes: Zolpidem can cause abnormal thinking and behavior changes, including hallucinations, agitation, and depersonalization.
• Worsening of depression: Zolpidem can worsen depression and increase the risk of suicidal thoughts and actions in primarily depressed patients.
• Respiratory depression: Zolpidem can cause respiratory depression, particularly in patients with compromised respiratory function, such as those with sleep apnea or COPD.

These concerns suggest that zolpidem may not be the best choice for this patient, and alternative treatments should be considered. 2 2

From the Research

Reasons to Avoid Zolpidem

• Zolpidem has been associated with an increased risk of falls in hospitalized patients with an OR of 4.28 (P <0.001) when prescribed short-term for insomnia 3.
• The relative risk (RR) 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 ADRs were central nervous system (CNS)-related such as confusion, dizziness, and daytime sleepiness 3.
• Suicide attempts and completion have been successfully linked with zolpidem use (OR 2.08; 95% CI 1.83-2.63) in patients regardless of the presence of comorbid psychiatric illness 3.
• There have been multiple cases reported of seizures following the withdrawal of zolpidem 3.

Alternative Treatment Options

• Ramelteon has a minimal adverse effect profile and is effective for sleep-onset latency and increased total sleep time, making it a valuable first-line option 4.
• Suvorexant improves sleep maintenance and has mild adverse effects, including somnolence; residual daytime sedation has been reported, however 4, 5.
• Low-dose doxepin is recommended for sleep maintenance insomnia 5.
• Cognitive behavioral therapy should always be the first line of treatment 4.

Special Considerations

• Zolpidem is considered a reasonable choice of therapy because it has a lower incidence of residual daytime sleepiness and risk of falls when compared to other drugs, but decisions for whether or not to prescribe it and the dosage should be made on a case-by-case basis, considering both the physical and psychiatric risks posed to the patient with insomnia 3.
• The FDA has classified zolpidem as a category C drug based on adverse outcomes seen in animal fetal development 3.