What are the effects of long-term use of diazepam (benzodiazepine)?

Effects of Long-Term Use of Diazepam

Long-term use of diazepam should be avoided due to substantial risks of cognitive impairment, falls, fractures, physical dependence, and potentially life-threatening withdrawal symptoms that far outweigh any therapeutic benefits. 1, 2, 3

Critical Adverse Effects

Cognitive and Psychomotor Impairment

• Diazepam causes persistent cognitive dysfunction including impaired memory, reduced processing speed, and visuospatial deficits that may not fully resolve even after discontinuation 4
• Psychomotor impairment significantly increases risk of unsafe driving and reduced functional independence, particularly in older adults 1
• Morning sedation and early morning motor incoordination are common, especially with diazepam's long elimination half-life 5

Falls and Fractures

• Benzodiazepines are a major independent risk factor for falls leading to femur fractures, with a dose-response relationship showing higher doses dramatically increase risk 6
• The risk increases 1.6-fold for current benzodiazepine users, and 3.4-fold with sudden dose increases 6
• Older adults (65+) face particularly elevated risk due to increased sensitivity and decreased metabolism 1

Physical Dependence and Tolerance

• Tolerance develops with long-term administration, requiring progressively higher doses to achieve the same therapeutic effect 1, 7, 3
• Approximately 50% of patients prescribed benzodiazepines for 12 months or longer develop signs of dependence 7
• GABA receptor downregulation occurs with chronic use, fundamentally altering brain neurochemistry 7

Life-Threatening Risks

Withdrawal Syndrome

• Abrupt discontinuation can precipitate acute withdrawal reactions that are life-threatening, including seizures, delirium tremens, hallucinations, and suicidality 3
• Acute withdrawal symptoms include severe anxiety, tremor, tachycardia, hypertension, gastrointestinal distress, and convulsions 3
• Protracted withdrawal syndrome can persist for weeks to more than 12 months, characterized by ongoing anxiety, cognitive impairment, depression, and insomnia 3

Respiratory Depression

• Concomitant use with opioids results in profound sedation, respiratory depression, coma, and death 3
• Respiratory depression risk is elevated in patients with baseline respiratory insufficiency 1

Accumulation and Toxicity

• Diazepam's active metabolites accumulate with prolonged use, especially in patients with renal dysfunction 1
• Delayed emergence from sedation results from saturation of peripheral tissues, advanced age, or hepatic dysfunction 1

Additional Serious Concerns

Associations with Other Conditions

• Observational studies suggest associations with increased all-cause mortality, dementia risk, and certain cancers, though causality requires further investigation 1, 8
• Increased infection incidence has been reported with chronic benzodiazepine use 1

Abuse and Addiction Potential

• Diazepam is a Schedule IV controlled substance with significant potential for abuse, misuse, and addiction 3
• Abuse commonly involves concomitant use of other medications, alcohol, and illicit substances, associated with serious adverse outcomes including death 3

Guideline Recommendations

Duration of Use

• Current consensus guidelines advise use of benzodiazepines solely on a short-term basis (ideally maximum 2-4 weeks) 1, 9
• Many FDA indications are only for short-term, as-needed use, not chronic daily administration 1
• Around half of patients are inappropriately prescribed benzodiazepines continuously for 12 months or longer 2

Special Populations

• The American Geriatrics Society Beers Criteria provides a strong recommendation to avoid benzodiazepines in older patients (65+) due to increased sensitivity, cognitive impairment, delirium risk, and falls 1, 2
• Elderly patients are 7-18 times more likely to be prescribed these medications despite heightened vulnerability 1

Discontinuation Strategy

Tapering Protocol

• Use a gradual taper to reduce withdrawal risk, typically reducing 25% of the daily dose each week, though slower tapers are often necessary 1
• The EMPOWER trial demonstrated 27% successful discontinuation using patient education about risks and gradual dose reduction over many weeks 1
• Never abruptly discontinue due to life-threatening withdrawal risk 3

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, meditation, and other non-pharmacological approaches are recommended 1, 2
• For anxiety, antidepressants may be more appropriate for long-term management 1

Clinical Bottom Line

The risks of long-term diazepam use—including cognitive impairment, falls, fractures, dependence, and potentially fatal withdrawal—substantially outweigh any therapeutic benefits. 1, 2, 3 If diazepam has been used long-term, implement a carefully monitored gradual taper with close follow-up, patient education, and consideration of evidence-based alternatives. 1, 5