Hazardous benzodiazepine regimens in the elderly: effects of half-life, dosage, and duration on risk of hip fracture.

OBJECTIVE While benzodiazepine treatment is known to increase the risk of hip fracture in older populations, controversy persists over which characteristics of benzodiazepine use (e.g., elimination half-life, dosage, duration of use) are most associated with such risks. METHOD The authors reviewed the health care utilization data of 1,222 hip fracture patients and 4,888 comparison patients frequency matched on the basis of age and gender (all were at least 65 years old). Patients were enrolled in Medicare as well as in the New Jersey Medicaid or Pharmaceutical Assistance to the Aged and Disabled programs. Benzodiazepine use, as well as other covariates, were assessed before the index date (which was either the date of hospital admission for hip fracture surgical repair or, for the comparison subjects, a randomly assigned, frequency-matched date). RESULTS All benzodiazepine doses > or =3 mg/day in diazepam equivalents significantly increased the adjusted risk of hip fracture by 50%. Significantly increased adjusted risks of hip fracture were seen during the initial 2 weeks of use (60% increase) and after more than 1 month of continuous use (80% increase) but not for 2-4 weeks of continuous use. Use of benzodiazepines other than long-acting agents significantly increased the risk of hip fracture by 50%. CONCLUSIONS Even at modest doses, including some low doses currently advocated in prescribing guidelines for older patients, treatment with benzodiazepines appears to increase the risk of hip fracture. Patients appear to be particularly vulnerable immediately after initiating therapy and after more than 1 month of continuous use. Benzodiazepines with shorter half-lives appear to be no safer than longer half-life agents. Clinicians should be aware of these risks and weigh them against potential benefits when prescribing for elderly patients.

[1]  A. LaCroix,et al.  Low-Dose Hydrochlorothiazide and Preservation of Bone Mineral Density in Older Adults , 2000, Annals of Internal Medicine.

[2]  D. Luchins Clinical Geriatric Psychopharmacology, 3rd ed. , 1999, American Journal of Psychiatry.

[3]  M. Tinetti,et al.  Drugs and Falls in Older People: A Systematic Review and Meta‐analysis: I. Psychotropic Drugs , 1999, Journal of the American Geriatrics Society.

[4]  W A Ray,et al.  Antidepressants and the risk of falls among nursing home residents. , 1998, The New England journal of medicine.

[5]  D. Bauer,et al.  Physical Activity and Osteoporotic Fracture Risk in Older Women , 1998, Annals of Internal Medicine.

[6]  B. Hemmelgarn,et al.  Benzodiazepine use and the risk of motor vehicle crash in the elderly. , 1997, JAMA.

[7]  F Sturmans,et al.  Benzodiazepines and the risk of falling leading to femur fractures. Dosage more important than elimination half-life. , 1995, Archives of internal medicine.

[8]  W. A. Smith,et al.  Prescribing benzodiazepines for noninstitutionalized elderly. , 1995, Canadian family physician Medecin de famille canadien.

[9]  S. Cummings,et al.  Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. , 1995, The New England journal of medicine.

[10]  C. I. Neutel,et al.  Medical events after a prescription for a benzodiazepine , 1995 .

[11]  W. Ray,et al.  Risk factors for hip fractures occurring in the hospital. , 1994, American journal of epidemiology.

[12]  L. Sata A TASK FORCE REPORT OF THE AMERICAN PSYCHIATRIC ASSOCIATION , 1994 .

[13]  D. Hallfors,et al.  The dependence potential of short half-life benzodiazepines: a meta-analysis. , 1993, American journal of public health.

[14]  R. Ivnik,et al.  Learning and memory impairment in older, detoxified, benzodiazepine-dependent patients. , 1993, Mayo Clinic proceedings.

[15]  R. Klineberg,et al.  Psychotropics, thiazide diuretics and hip fractures in the elderly , 1993, The Medical journal of Australia.

[16]  G. Gottlieb,et al.  Conventional pharmacologic treatment for patients with Alzheimer's disease , 1993 .

[17]  W A Ray,et al.  Psychoactive drugs and the risk of injurious motor vehicle crashes in elderly drivers. , 1992, American journal of epidemiology.

[18]  R. Deyo,et al.  Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. , 1992, Journal of clinical epidemiology.

[19]  D. Wysowski,et al.  Outpatient use of prescription sedative-hypnotic drugs in the United States, 1970 through 1989. , 1991, Archives of internal medicine.

[20]  D. Kiel,et al.  Thiazide diuretics and the risk of hip fracture. Results from the Framingham Study. , 1991 .

[21]  A. LaCroix,et al.  Thiazide diuretic agents and the incidence of hip fracture. , 1990, The New England journal of medicine.

[22]  W A Ray,et al.  Benzodiazepines of long and short elimination half-life and the risk of hip fracture. , 1989, JAMA.

[23]  S. Silverman,et al.  Decreased incidence of hip fracture in Hispanics, Asians, and blacks: California Hospital Discharge Data. , 1988, American journal of public health.

[24]  G. Sorock,et al.  Benzodiazepine sedatives and the risk of falling in a community-dwelling elderly cohort. , 1988, Archives of internal medicine.

[25]  S. Golombok,et al.  Cognitive impairment in long-term benzodiazepine users , 1988, Psychological Medicine.

[26]  M. Scharf,et al.  Comparative amnestic effects of benzodiazepine hypnotic agents. , 1988, The Journal of clinical psychiatry.

[27]  Á. Nagy Long‐term treatment with benzodiazepines: Theoretical, ideological and practical aspects , 1987, Acta psychiatrica Scandinavica. Supplementum.

[28]  S. Whitcup,et al.  Unrecognized Drug Dependence in Psychiatrically Hospitalized Elderly Patients , 1987, Journal of the American Geriatrics Society.

[29]  L. Melton,et al.  Psychotropic drug use and the risk of hip fracture. , 1987, The New England journal of medicine.

[30]  H. Curran Tranquillising memories: A review of the effects of benzodiazepines on human memory , 1986, Biological Psychology.

[31]  C. Swift Postural instability as a measure of sedative drug response. , 1984, British journal of clinical pharmacology.

[32]  D. Greenblatt,et al.  Toxicity of high‐dose flurazepam in the elderly , 1977, Clinical pharmacology and therapeutics.

[33]  Boston Collaborative Drug Surveillance Program Clinical depression of the central nervous system due to diazepam and chlordiazepoxide in relation to cigarette smoking and age. , 1973, The New England journal of medicine.