Secretion. This in turn affects synaptic function and cognitive performance! The extent to which this applies to other common genetic polymorphisms in neurotrophic factors and or neurotransmitters is not known. However studies such as this show the power of linking clinical performance to cell culture systems, and by so doing raises many questions on the origins of disease heterogeneity. -RAB The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger SR. CELL 2003: 112: 257-269. EPILEPSY: and alcohol dependence ? You might argue that I stepping outside my remit of talking about epilepsy this month but this paper has gladdened my heart in an area where to date, therapeutic nihilism has been the rule. Alcohol is the commonest cause of seizures in young adults in many societies and when I faced with a patient with alcohol-related seizures I vacillate between telling the patient to come back when they have stopped drinking and feeling sorry for them and giving treatment even though it is of proven benefit. Among the existing drugs, do you give one that is metabolised in the liver and whose levels may fluctuate wildly, one that may precipitate hepatic encephalopathy or one that is renally excreted? Here is a possible way forward. The rationale for the paper is that alcohol cravings are thought to be mediated by dopaminergic projections from the tegmentum to the nucleus accumbens and cortex. Alcohol reduces GABA receptor activity in the tegmentum and may enhance this dopaminergic activity. Chronic alcoholics may have increased glutamate activity. Topiramate seems to enhance GABAA activity via a non-benzodiazepine site and reduce dopamine activity so block the effects of alcoholism. In this double-blind study 150 drinkers were randomly allocated to topiramate or placebo and followed up for 12 weeks. Topiramate was titrated to 300mg over 8 weeks. The patients were given "brief behavioural compliance-enhancement treatment" by a nurse to ensure they took the drugs. I not quite sure what this means but it sounds either scary or exciting, depending on your inclinations. The measures used were self-reporting of the number of drinks per day, the number of drinks per drinking day, the number of abstinent days, the number of heavy drinking days, gamma GT, self-reported craving, drinking obsessions and a measure called automaticity of drinking. Dropouts were high a statistical not a psychosocial observation ; . Twenty-seven left the placebo and 20 the treatment arm, mostly because they were lost to follow-up or just chose to leave the study. Adverse events were few. All the measures improved in the placebo arm. Just making drinkers aware of what they are doing and engaging them in research, taking an interest perhaps, helps in the short term. The topiramate group was dramatically better on all the measures, for example 45% abstinent days versus 15%, probability of heavy drinking 35% versus 75% for placebo by the end of the study. This is only a short term study but it is not often that one sees such clear-cut results and the graphs of placebo and topiramate diverge impressively to the end of the study. Of course the idea that 300mg of topiramate is ever blind to the consumer is a little naive but I do not think this negates the results of a potentially important study. It so happens this study exactly coincides with topiramate receiving its monotherapy licence in the UK - any Janssen-Cilag reps reading this review can contact me for the number of an account in an obscure Swiss bank. -MM Oral topiramate for the treatment of alcohol dependence: a randomised controlled trial. Johnson BA, Ait-Daoud N, Bowden CL, DiClimente CC, Roache JD, Lawson K, Javors MA and Ma JZ. LANCET 2003; 361: 1677-85.