National High Blood Pressure Education Program.

Clinical Trials: A Practical Approach

Neurobiological research with animals strongly suggests that the brain systems which mediate emotion overlap with those that mediate cognition to such a degree that it is difficult, if not impossible, to maintain any clear distinction between them. Possible reasons for this overlap are discussed; and a model of brain systems that simultaneously subserve emotion and cognition is presented. The model postulates the existence of three fundamental systems of this kind in the mammalian brain: a behavioural approach system, a fight/flight system, and a behavioural inhibition system. The neuropsychology of each of these systems is briefly presented.

Brain systems that mediate both emotion and cognition.

Objectives To investigate the relation between the risk of Alzheimer's disease and exposure to benzodiazepines started at least five years before, considering both the dose-response relation and prodromes (anxiety, depression, insomnia) possibly linked with treatment.

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Benzodiazepine use and risk of Alzheimer’s disease: case-control study

Aims To re-examine various aspects of the benzodiazepines (BZDs), widely prescribed for 50 years, mainly to treat anxiety and insomnia. It is a descriptive review based on the Okey Lecture delivered at the Institute of Psychiatry, King's College London, in November 2010.

Methods  A search of the literature was carried out in the Medline, Embase and Cochrane Collaboration databases, using the codeword ‘benzodiazepine(s)’, alone and in conjunction with various terms such as ‘dependence’, ‘abuse’, etc. Further hand-searches were made based on the reference lists of key papers. As 60 000 references were found, this review is not exhaustive. It concentrates on the adverse effects, dependence and abuse.

Results  Almost from their introduction the BZDs have been controversial, with polarized opinions, advocates pointing out their efficacy, tolerability and patient acceptability, opponents deprecating their adverse effects, dependence and abuse liability. More recently, the advent of alternative and usually safer medications has opened up the debate. The review noted a series of adverse effects that continued to cause concern, such as cognitive and psychomotor impairment. In addition, dependence and abuse remain as serious problems. Despite warnings and guidelines, usage of these drugs remains at a high level. The limitations in their use both as choice of therapy and with respect to conservative dosage and duration of use are highlighted. The distinction between low-dose ‘iatrogenic’ dependence and high-dose abuse/misuse is emphasized.

Conclusions  The practical problems with the benzodiazepines have persisted for 50 years, but have been ignored by many practitioners and almost all official bodies. The risk–benefit ratio of the benzodiazepines remains positive in most patients in the short term (2–4 weeks) but is unestablished beyond that time, due mainly to the difficulty in preventing short-term use from extending indefinitely with the risk of dependence. Other research issues include the possibility of long-term brain changes and evaluating the role of the benzodiazepine antagonist, flumazenil, in aiding withdrawal.

H V Curran

Papers

Tranquillising memories: a review of the effects of benzodiazepines on human memory.