What are the long-term risks of benzodiazepines (BZDs) use?

Long-Term Risks of Benzodiazepines

Benzodiazepines should only be used short-term (2-4 weeks maximum) because long-term use causes substantial, well-documented harms including cognitive impairment, falls with fractures, dependence with potentially life-threatening withdrawal, respiratory depression (especially with opioids), and possibly increased mortality and dementia risk. 1, 2, 3

Critical Safety Risks

Cognitive and Psychomotor Impairment

• Benzodiazepines cause sedation, cognitive decline, reduced mobility, and unsafe driving skills that persist throughout treatment. 1, 3, 4
• Morning sedation and motor incoordination are particularly problematic with long-acting agents like diazepam due to accumulation of active metabolites. 2
• These effects worsen functional independence and quality of life, especially in older adults. 3, 5

Falls and Fractures

• The American Geriatrics Society provides a strong recommendation to avoid benzodiazepines in patients aged 65+ specifically because they significantly increase fall and fracture risk. 6, 1, 2
• This risk exists regardless of whether short- or long-acting benzodiazepines are used—there is no clear safety difference between formulations. 6
• Falls represent one of the most serious morbidity risks, directly impacting quality of life and mortality in elderly patients. 1, 7

Respiratory Depression and Mortality

• When combined with opioids, benzodiazepines cause dangerous cumulative and synergistic respiratory depression leading to coma and death. 6, 3
• Respiratory depression risk is elevated even without opioids in patients with baseline respiratory insufficiency. 2
• Observational studies suggest associations with increased all-cause mortality, though causality requires further investigation. 2

Dependence and Withdrawal

• Physical dependence develops with regular use, and withdrawal symptoms can be life-threatening (including seizures) if benzodiazepines are stopped abruptly. 1, 8
• Approximately 50% of patients prescribed benzodiazepines continue them for at least 12 months continuously—a practice explicitly not recommended by clinical guidelines. 6, 3
• Dependence is a serious, often unrecognized problem in the elderly that can lead to medical complications if untreated. 7, 5

Additional Long-Term Harms

Emerging Concerns

• Chronic benzodiazepine use may increase dementia risk, though this association requires further research to establish causality. 2, 7
• Increased infection incidence has been reported with chronic use. 2
• Associations with certain cancers have been observed but remain under investigation. 2

Accumulation Effects

• Active metabolites accumulate with prolonged use, especially in patients with renal or hepatic dysfunction. 2, 3
• Delayed emergence from sedation results from saturation of peripheral tissues, advanced age, or liver disease. 2

Guideline-Based Duration Recommendations

Current consensus guidelines from the American Geriatrics Society, American College of Physicians, and other major medical societies advise benzodiazepine use solely on a short-term basis—ideally maximum 2-4 weeks. 1, 2, 3

• Many FDA indications specify short-term, as-needed use only, not chronic daily administration. 2
• Prescriptions should be limited to a few days, occasional/intermittent use, or courses not exceeding 2-4 weeks. 3
• The U.S. Department of Veterans Affairs and Department of Defense clinical practice guidelines explicitly advise against benzodiazepines for chronic insomnia because risks substantially outweigh benefits. 1

High-Risk Populations Requiring Special Caution

Older Adults (Age 65+)

• The American Geriatrics Society Beers Criteria provides a strong recommendation to avoid benzodiazepines in older patients due to increased sensitivity, decreased metabolism, cognitive impairment, delirium risk, and falls. 1, 2, 3
• Elderly patients experience greater risks of sedation, prolonged drug effects, and reduced functional independence. 3, 5
• Older females with co-morbid medical and psychiatric conditions taking multiple medications form the highest-risk group. 5

Patients with Cognitive Impairment

• Benzodiazepines should be avoided in patients with uremic encephalopathy or delirium as they worsen the underlying condition and prevent accurate clinical assessment. 3

Polypharmacy Contexts

• Polypharmacy is a major risk factor for adverse outcomes. 7
• Particular attention should be given to patients taking four or more medications. 6
• Avoid combining benzodiazepines with antipsychotics due to risk of oversedation, respiratory depression, and fatalities. 3

Management Strategy When Long-Term Use Has Occurred

Discontinuation Approach

• Use a gradual taper to reduce withdrawal risk, typically reducing 25% of the daily dose each week, though slower tapers are often necessary. 2, 8
• The EMPOWER trial demonstrated 27% successful discontinuation using patient education about risks and gradual dose reduction over many weeks. 2
• Unless the patient is elderly, switch to a long-acting benzodiazepine during both withdrawal and maintenance therapy to lower seizure risk. 8

Alternative Treatments

• Cognitive-behavioral therapy, problem-solving therapy, and supportive psychotherapy should be pursued as first-line alternatives. 1, 2
• Integrative strategies including relaxation techniques and meditation are recommended. 1, 2
• For anxiety, antidepressants may be more appropriate for long-term management. 2
• Brief cognitive therapy relying on psychoeducation and motivational enhancement is particularly useful in elderly patients. 7

Success Rates

• Reported success rates of deprescribing interventions range between 27-80%, with variability attributed to methodological differences. 9
• Discontinuation is feasible in elderly patients with adequate psychotherapeutic or pharmacological strategies and can lead to long-term abstinence. 7

Common Pitfalls to Avoid

• Do not assume short-acting benzodiazepines are safer—active metabolites still accumulate and elimination is prolonged, especially in renal failure. 3
• Do not use benzodiazepines to manage encephalopathy or delirium itself, as they worsen the condition. 3
• Do not continue prescribing beyond 2-4 weeks without a compelling, documented reason and plan for discontinuation. 2, 3
• Patients should be informed of the temporary nature of treatment and alternative options before initiating therapy. 1