title: Adverse performance effects of acute lorazepam administration in elderly long-term users: pharmacokinetic and clinical predictors.
abstract: BACKGROUND
  The benzodiazepine lorazepam is widely utilized in the treatment of elderly individuals with anxiety disorders and related conditions. Negative effects of acute lorazepam administration on cognitive performance, especially memory, have been reported in both previously untreated elderly and in individuals who have received short term (up to three weeks) treatment with therapeutic doses. However, it remains unclear if these adverse cognitive effects also persist after long-term use, which is frequently found in clinical practice.
  
  
  METHODS
  Cognitively intact elderly individuals (n=37) on long-term (at least three months) daily treatment with lorazepam were studied using a double-blind placebo-controlled cross-over study design. Subjects were administered their highest daily unit dose of lorazepam (0.25-3.00 mg) or placebo on different days, approximately 1 week apart in a random order, and were assessed on memory, psychomotor speed, and subjective mood states.
  
  
  RESULTS
  Subjects had significantly poorer recall and slowed psychomotor performance following acute lorazepam administration. There were no significant effects on self-ratings of mood, sedation, or anxiety in the whole group, but secondary analyses suggested a differential response in subjects with Generalized Anxiety Disorder.
  
  
  CONCLUSIONS
  The reduced recall and psychomotor slowing that we observed, along with an absence of significant therapeutic benefits, following acute lorazepam administration in elderly long-term users reinforces the importance of cognitive toxicity as a clinical factor in benzodiazepine use, especially in this population.
authors.affiliation: Nathan Kline Institute, Orangeburg, NY, USA; New York University School of Medicine, New York, NY, USA. Electronic address: pomara@nki.rfmh.org.
authors.forename: Nunzio
authors.initials: N
authors.lastname: Pomara
authors.affiliation: Nathan Kline Institute, Orangeburg, NY, USA.
authors.forename: Sang Han
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Nathan Kline Institute, Orangeburg, NY, USA; New York University School of Medicine, New York, NY, USA; Liverpool Hope University, Liverpool, UK.
authors.forename: Davide
authors.initials: D
authors.lastname: Bruno
authors.affiliation: Nathan Kline Institute, Orangeburg, NY, USA; Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Silber
authors.affiliation: Tufts University School of Medicine, Boston, MA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Greenblatt
authors.affiliation: Nathan Kline Institute, Orangeburg, NY, USA; New York University School of Medicine, New York, NY, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Petkova
authors.affiliation: Nathan Kline Institute, Orangeburg, NY, USA; New York University School of Medicine, New York, NY, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Sidtis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014151:Anti-Anxiety Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D001007:Anxiety / Q000097:blood / Q000188:drug therapy; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004644:Emotions; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008140:Lorazepam / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced*; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000187:drug effects*
chemical_list: D014151:Anti-Anxiety Agents; D008140:Lorazepam
keywords: Aging; Benzodiazepines; Cognitive toxicity; Lorazepam; Memory loss; Psychomotor slowing