For the treatment of anxiety states, the γ-aminobutyric acid (GABA)ergic action of some anticonvulsants, eg, pregabalin and gabapentin, may be more decisive.16

However, these acute receptor-transmitted effects are largely insufficient to explain, eg, long-term stabilization of mood such as that provided by lithium. During the last decade, it has been demonstrated that not only lithium, but also valproate and, in part, carbamazepine, regulate numerous factors enhancing cellular plasticity and resilience, Inhibitors,research,lifescience,medical including inositol biosynthesis (MIP synthase), cyclic adenosine monophosphate (c-AMP) response element binding protein, brain-derived neurotrophic factor (BDNF), the extracellular signal-regulated kinase pathway, the

arachidonic acid pathway, the cytoprotective protein bcl-2 and mitogen-activated protein kinases.17-24 All these intracellular actions may contribute to preventing a kindling process which otherwise leads to a Inhibitors,research,lifescience,medical constant decline of the threshold for relapses. The amygdala kindling model, originally developed to explain progression of epileptic seizures,25 may also be applicable to affective episodes, panic attacks and anxiety states, or alcohol and drug relapses.26 Substance abuse Alcohol Although their MLN2238 mechanism of action is not completely understood, the efficacy of anticonvulsants Inhibitors,research,lifescience,medical in the alcohol withdrawal syndrome is thought to be related to their ability to inhibit, kindling and facilitate GABA inhibitory neurotransmission. A recent Cochrane meta-analysis of 48 studies involving 3610 subjects compared different ACs with placebo for alcohol withdrawal, Therapeutic success Inhibitors,research,lifescience,medical tended to be more common among the anticonvulsant-treated patients (relative risk (RR) 1.32; 95% confidence interval Inhibitors,research,lifescience,medical (CI) 0.92 to 1.91), and ACs tended to show a protective benefit, against seizures (RR 0.57; 95% CI 0.27 to 1.19), but

no effect reached formal statistical significance.27 Nevertheless, there is limited positive evidence for some heptaminol ACs. Carbamazepine28 and oxcarbazepine29 alone or, especially in Germany, in combination with tiapridc,30 are frequently used for alcohol withdrawal because they reduce the risk of convulsions and, especially in the case of carbamazepine, cause an initial sedation when titrated rapidly. For oxcarbazepine, open data also suggest anticraving effects in sober alcoholics.31 There are also some reports on the use of valproate for alcohol withdrawal. Myrick et al32 reported comparable effects of lorazepam and valproate in reducing alcohol withdrawal symptoms in an open trial. In a double-blind randomized study, Tress et al33 compared valproate with clomethiazol, observing no difference in somatic symptoms and the absence of severe delirious states with both medication.