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Sedative effects and impaired learning and recall after single oral doses of lorazepam
Author(s) -
Shader Richard I,
Dreyfuss Daniel,
Gerrein John R,
Harmatz Jerold S,
Allison Shelley J,
Greenblatt David J
Publication year - 1986
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1986.90
Subject(s) - lorazepam , dosing , sedation , placebo , anesthesia , sedative , medicine , crossover study , recall , psychology , pharmacology , alternative medicine , pathology , cognitive psychology
Seven healthy subjects received oral placebo, 1.5 mg lorazepam, or 3.0 mg lorazepam in a single‐dose, three‐way crossover study. Plasma lorazepam concentrations and subjects' self‐rated sedative effects were evaluated at multiple points during 24 hours after each dose. Information acquisition and recall was studied by use of a 16‐item word list at 3 and 24 hours after dosing. Lorazepam plasma concentrations were proportional to dose. Self‐rated sedation was maximal 2 to 3 hours after lorazepam dosing, persisted for 8 hours, and was dose dependent in intensity; no significant sedation occurred with placebo. At 3 hours after placebo dosing, subjects learned a mean 96% of words presented during six trials; this was reduced to 79% and 62% after lorazepam, 1.5 and 3.0 mg, respectively (F = 6.2; P < 0.02). Twenty‐four hours after placebo, subjects recalled 92% of words presented the previous day, then improved to 99% after six relearning trials. After 1.5 and 3.0 mg lorazepam, however, only 52% and 44% of words were initially recalled from the previous day. Thus single oral doses of lorazepam within the therapeutic range produce dose‐dependent sedation and impairment of information acquisition and recall. Clinical Pharmacology and Therapeutics (1986) 39, 526–530; doi: 10.1038/clpt.1986.90