title: Long-term use of benzodiazepines in participants with comorbid anxiety and alcohol use disorders.
abstract: BACKGROUND
  Although the only widely accepted role for benzodiazepines in alcohol dependence is the treatment of withdrawal syndromes, they are frequently prescribed outside of this clinical setting. There is little empirical evidence to guide the rational use of benzodiazepines in the common clinical situation where anxiety disorders are comorbid with alcohol use disorders (AUD). Since January 1989, the Harvard Anxiety Research Program has naturalistically monitored the prospective clinical course of people with anxiety disorders, some of whom had a history of AUD. Earlier research showed that the use of benzodiazepines was not significantly associated with the presence or absence of a history of an AUD over the first year of follow-up. This report extends that investigation.
  
  
  METHODS
  Using standard parametric analytic methods, patterns of benzodiazepine use (routinely prescribed medication and as-needed [PRN] use) among participants receiving benzodiazepine treatment was prospectively examined over the course of 12 years. Differences in benzodiazepine usage patterns were examined in each year of follow-up between participants who did (n=120) and did not (n=425) have a new episode of AUD. Using proportional hazards regression analysis, benzodiazepine usage levels were examined as predictors of recovery and recurrence of AUD. Additionally, random-effects regression analyses were used to examine the patterns of benzodiazepine use before and after the onset of a prospectively observed episode of AUD.
  
  
  RESULTS
  Benzodiazepine usage levels remained stable for the full sample over the course of the 12 years. Benzodiazepine use did not distinguish participants who had a new AUD from those who did not. Over the 12 years of follow-up, participants who had an AUD used more PRN medication in years five to eight. This difference reached statistical significance but was not clinically significant. Benzodiazepine usage levels did not predict recovery or recurrence in AUD subjects. Neither the total dose nor the PRN usage of benzodiazepines was significantly associated with the onset of AUD, but when combined into a measure of any benzodiazepine use, a relationship between increased use and the onset of AUD emerged.
  
  
  CONCLUSIONS
  For participants in the Harvard Anxiety Research Program with comorbid alcohol dependence and anxiety disorders, there was little association between the use of benzodiazepines and the occurrence of a new AUD. Neither was there a temporal relationship between the use of benzodiazepines and the onset of a new AUD. Whether or not this finding extends to a broader patient population or a group of people who present to addictions treatment awaits further investigation.
authors.affiliation: Southern Arizona VA Health Care System, University of Arizona Health Sciences Center, Department of Psychiatry, Tucson, Arizona 85723, USA. timothy.mueller@med.va.gov
authors.forename: Timothy I
authors.initials: TI
authors.lastname: Mueller
authors.forename: Maria E
authors.initials: ME
authors.lastname: Pagano
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Rodriguez
authors.forename: Steven E
authors.initials: SE
authors.lastname: Bruce
authors.forename: Robert L
authors.initials: RL
authors.lastname: Stout
authors.forename: Martin B
authors.initials: MB
authors.lastname: Keller
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000453:epidemiology / Q000534:rehabilitation*; D001008:Anxiety Disorders / Q000453:epidemiology / Q000534:rehabilitation*; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008134:Long-Term Care; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D013375:Substance Withdrawal Syndrome / Q000534:rehabilitation
chemical_list: D001569:Benzodiazepines