Risks of Benzodiazepines
Benzodiazepines carry substantial risks including dependence, falls, cognitive impairment, respiratory depression (especially when combined with opioids or alcohol), and increased mortality—with chronic use being significantly more dangerous than intermittent use, particularly in older adults. 1, 2
Primary Safety Concerns
Dependence and Withdrawal
Benzodiazepines carry a well-established risk of physical and psychological dependence, particularly with long-term use 1. The evidence shows that:
- Approximately half of patients prescribed benzodiazepines in England were treated continuously for at least 12 months, a practice not recommended by clinical guidelines 1
- Withdrawal symptoms (anxiety, sleep disturbances, agitation) are common and often prolonged when discontinuing 3
- Sudden cessation leads to physical and psychological withdrawal symptoms requiring careful tapering and support 1
Mortality Risk
The mortality data is particularly concerning and dose-dependent 4, 5:
- Very high-dose use (≥3.0 DDDs/day) carries a 6-fold increased risk of overdose deaths compared to non-use 4
- Medium to high-dose use (1.0-<3.0 DDDs/day) shows a 3-fold increased risk of overdose 4
- Short-term use paradoxically shows elevated mortality risk (HR 2.26 in those <80 years), possibly reflecting acute illness or indication bias 5
- Low-dose use (<1.0 DDD/day) does not show elevated all-cause mortality risk 4
The highest mortality risks occur with potentially preventable deaths:
- Overdoses: 6.18-fold increased risk with very high doses 4
- Suicides: 4.46-fold increased risk 4
- Accidents: 3.77-fold increased risk 4
Falls and Fractures
The American Geriatrics Society Beers Criteria strongly recommends avoiding benzodiazepines in older adults due to increased sensitivity and substantial risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes 2. The evidence shows:
- Chronic use increases fall-related hospitalizations/ED visits by 13% compared to intermittent use (HR 1.13) 6
- Hip fractures show significant excess risk with chronic use 6
- Falls occur in 4.6% of chronic users versus 3.2% of intermittent users during follow-up 6
Cognitive and Neurological Effects
Benzodiazepines cause significant CNS-related adverse effects including 3:
- Sedation and confusion
- Memory loss and cognitive impairment
- Depression
- Motor incoordination
Long-term treatment leads to risks of adverse neurological effects beyond just dependence 1.
Respiratory Depression and Drug Interactions
Although benzodiazepines have relatively low toxicity when used alone, combining them with opioids dramatically increases overdose risk through cumulative and synergistic effects on respiratory depression 1. This combination is particularly dangerous and accounts for many preventable deaths 7.
Similarly, combining benzodiazepines with alcohol increases risk of harm substantially 7.
Chronic vs. Intermittent Use
A critical distinction emerges from the evidence: chronic daily use in older adults is associated with higher risks of falls, fractures, hospitalizations, and death compared to intermittent use 3, 6. The comparative study shows:
- Significant excess risks for most outcomes with chronic use 6
- Long-term care admission rates higher with chronic use 6
- Adjustment for dosage has minimal impact, suggesting duration matters independently 6
High-Risk Populations
Factors that substantially increase risk of adverse effects and misuse include 3:
- Other substance use disorders
- Concomitant CNS medications (especially opioids)
- CNS or pulmonary diseases
- Age ≥65 years (though risks decrease somewhat after age 80) 5
Clinical Implications
For patients already on long-term benzodiazepines, slow tapering over weeks to months (or longer) is essential to minimize withdrawal symptom intensity 3. Adjunctive treatment with antiepileptics, antidepressants, or pregabalin can lessen withdrawal symptoms 3.
The evidence strongly supports that benzodiazepines should be reserved for short-term treatment of severe anxiety and insomnia only, with careful monitoring for the development of dependence 1. The declining prescription rates in England (from 10.5 million to 7.7 million between 2008-2018) reflect growing recognition of these risks 1.
Misuse accounts for 17.2% of all benzodiazepine use in the United States, with more than 30 million adults reporting use within the past year 3, 8, highlighting this as a significant public health concern requiring improved guidance, monitoring, and patient care 1.