ABSTRACT
Benzodiazepines (BZDs) became widely available in the 1960s and have been prescribed to hundreds of millions of people over the past four decades. BZDs are effective in the treatment of insomnia, anxiety, epileptic disorders, for skeletal muscle relaxation, and for the induction and maintenance of anesthesia. The rapid onset and reliable efficacy of their therapeutic actions and their favorable side-effect profile have led to a continued large prescription. BZDs are less toxic in overdose than alternatives; they are safe and have little liability for abuse among patients without a history of abuse.1 Despite their dubious reputation, due to the risk of dependence, withdrawal syndromes, their use as a ‘date-rape drug,’ for drug-facilitated robbery and chemical submission,2 their risk-benefit ratio is rather positive. Nevertheless, a common side effect of this class of drugs is dose-related anterograde amnesia, i.e. forgetfulness for events that occurs following drug intake and which persists for several hours. This effect was initially reported in the 1980s after intravenous administration of various BZDs as pre-surgery medications and further extended to their oral intake.3 The intensity of the amnesic effect depends on the nature of the molecule (potency, elimination half-life, onset of action), dose, route of administration, acute or chronic administration, and the subject’s profile.4 It appears to be a robust phenomenon, generalizing across species and experimental conditions. The greatest amnesic effect is observed after administration of a single dose of a BZD with short elimination half-life and rapid onset of action to benzodiazepine-naive subjects. It was assumed that the mechanism of memory impairment was a failure of memory consolidation, and this deficit is transitory. Retrograde amnesia, i.e. memory loss for events prior to administration of drugs, has not been observed with BZDs. In fact, BZDs may even facilitate retrieval of information learned prior to drug administration, a phenomenon known as retrograde facilitation, which reduces interference of additional information acquired post-drug ingestion.5 Recently, Pomara et al6 demonstrated a dose-dependent retrograde facilitation of
verbal memory in healthy elderly persons after acute oral lorazepam administration – a property associated with the amnesic and sedative effects produced by the drug.
