Zolpidem (Ambien) Side Effects
Zolpidem can cause numerous side effects ranging from common drowsiness and dizziness to serious complex sleep behaviors that have caused injuries and deaths, with women and elderly patients at higher risk due to slower drug clearance. 1, 2
Common Side Effects
Serious Adverse Effects
Complex Sleep Behaviors
- Getting out of bed while not fully awake and performing activities without awareness or memory, including:
These complex behaviors can lead to serious injury or death and are a major concern with zolpidem use 1.
Cognitive and Neuropsychiatric Effects
- Next-day cognitive impairment, particularly when:
- Taken with less than 7-8 hours of sleep opportunity
- Used at higher doses
- Combined with other CNS depressants 2
- Memory loss/amnesia 3, 4
- Confusion 3, 2
- Abnormal thoughts and behavior 1
- Hallucinations and sensory distortions 4
- Agitation 1
- Worsening depression 1
- Suicidal thoughts or actions 1, 5
Physical Risks
- Falls and fractures, especially in elderly patients (5-fold increase in risk) 3, 2, 5
- Motor vehicle accidents 3
- Severe allergic reactions including swelling of tongue, throat, and difficulty breathing 1
Special Population Considerations
Women
- Women clear zolpidem 45% slower than men, resulting in 45% higher blood levels 2
- FDA recommends lower doses for women (5 mg immediate-release; 6.25 mg extended-release) compared to men (10 mg immediate-release; 12.5 mg extended-release) 2
Elderly Patients
- Increased sensitivity to cognitive effects 2
- Higher risk of falls, confusion, and complex sleep behaviors 2
- Lower recommended dose (5 mg immediate-release) 2
- American Geriatrics Society suggests avoiding zolpidem in elderly patients 2
Pregnancy and Breastfeeding
- Zolpidem is FDA category C for pregnancy 5
- May cause breathing difficulties or excess sleepiness in newborns if taken late in pregnancy 1
- Passes into breast milk 1
Risk Factors for Adverse Effects
- Female gender 2, 4
- Advanced age 2, 4
- Higher doses (≥10 mg) 2, 4
- Concomitant use of SSRIs or other CNS depressants 4, 6
- Alcohol consumption 1
- Low serum albumin (leads to higher free zolpidem levels) 4
- Cytochrome P450 isoenzyme inhibition from drug interactions 4
Withdrawal Effects
After stopping zolpidem, patients may experience for 1-2 days:
- Rebound insomnia
- Trouble sleeping
- Nausea
- Flushing
- Lightheadedness
- Uncontrolled crying
- Vomiting
- Stomach cramps
- Panic attacks
- Nervousness 1
In rare cases, seizures have been reported following withdrawal, particularly with high doses 5.
Precautions
- Take only if able to stay in bed for 7-8 full hours 1
- Take immediately before bedtime, not earlier 1
- Use lowest effective dose, especially for women and elderly 2
- Do not take with alcohol 1
- Do not take with other sedatives unless directed by healthcare provider 1
- Take on an empty stomach for faster sleep onset 1
The American Academy of Sleep Medicine and American College of Physicians note that while zolpidem is effective for short-term insomnia treatment, its use should be carefully considered due to the risk of adverse effects, particularly in vulnerable populations 3, 2.