The aim of this review is to establish the relationship between treatment with hypnotics and the risk of postural instability and as a consequence, falls and hip fractures, in the elderly. A review of the literature was performed through a search of the MEDLINE, Ingenta and PASCAL databases from 1975 to 2005. We considered as hypnotics only those drugs approved for treating insomnia, i.e. some benzodiazepines and the more recently launched 'Z'-compounds, i.e. zopiclone, zolpidem and zaleplon. Large-scale surveys consistently report increases in the frequency of falls and hip fractures when hypnotics are used in the elderly (2-fold risk). Benzodiazepines are the major class of hypnotics involved in this context; falls and fractures in patients taking Z-compounds are less frequently reported, and in this respect, zolpidem is considered as at risk in only one study. It is important to note, however, that drug adverse effect relationships are difficult to establish with this type of epidemiological data-mining. On the other hand, data obtained in laboratory settings, where confounding factors can be eliminated, prove that benzodiazepines are the most deleterious hypnotics at least in terms of their effects on body sway. Z-compounds are considered safer, probably because of their pharmacokinetic properties as well as their selective pharmacological activities at benzodiazepine-1 (BZ(1)) receptors. The effects of hypnotics on balance, gait and equilibrium are the consequence of differential negative impacts on vigilance and cognitive functions, and are highly dose- and time-dependent. Z-compounds have short half-lives and have less cognitive and residual effects than older medications. Some practical rules need to be followed when prescribing hypnotics in order to prevent falls and hip fractures as much as possible in elderly insomniacs, whether institutionalised or not. These are: (i) establish a clear diagnosis of the sleep disorder; (ii) take into account chronic conditions leading to balance and gait difficulties (motor and cognitive status); (iii) search for concomitant prescription of psychotropics and sedatives; (iv) use half the recommended adult dosage; and (v) declare any adverse effect to pharmacovigilance centres. Comparative pharmacovigilance studies focused on the impact of hypnotics on postural stability are very much needed.

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Tiapride is not different from haloperidol in the treatment of agitation and aggressiveness in elderly patients and better tolerated, in particular with significantly fewer extrapyramidal symptoms.

Ca}eine is a widely!consumed psychoactive substance whose stimulant e}ects on mood\ attention and performance are largely recognised[ The central nervous system pharmacodynamic pro_le of a single oral dose of a new slow release "SR# ca}eine formulation "599 mg# was assessed in a randomised\ double!blind\ crossover\ placebo!controlled study[ Twelve young\ health\ male\ sleep!deprived "for 25 h# subjects were studied using EEG and various measures of psychomotor and cognitive functions\ including critical~icker fusion "CFF#\ choice reaction task "CRT#\ tracking\ continuous performance task "CPT#\ Stroop test\ body sway and subjective evaluation "Stanford Sleepiness Scale#[ Ca}eine signi_cantly "p ³ 9=94# antagonised the detrimental e}ects of sleep!deprivation on EEG "i[e[ produced a signi_cant decrease in delta and theta relative power and a signi_cant increase in alpha and beta "01Ð39 Hz# relative power# and psychomotor performance "signi_cant increase in speed of reaction on the CRT and Stroop tests\ signi_cant decrease in body sway\ signi_cant increase in accuracy of the CPT and signi_cant reduction in subjective sedation# compared to placebo[ The e}ect peaked 3 h after dosing and was maintained until the end of sleep deprivation "i[e[ 13 h after dosing#[ In conclusion\ the present results demonstrate that a single dose of ca}eine SR possesses alerting e}ects which are able to reverse the deleterious e}ect of 25 h sleep deprivation for at least 13 h[

Six severe epileptic patients developed stuporous encephalopathy with marked cognitive impairment when topiramate (TPM) and sodium valproate (VPA) were coprescribed for five patients, and when monotherapy with TPM was introduced for one patient. In four patients, ammonaemia increased and then returned to normal after TPM or VPA withdrawal. This severe potential side effect must be recognized. Moreover two distinct mechanisms might explain this toxicity: (1). a pharmacokinetic interaction between VPA and TPM, leading to hyperammonaemia, (2). a pharmacodynamic mechanism due to a direct toxicity of TPM in at-risk epileptic patients.

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