European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
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Eur Neuropsychopharmacol · Nov 2013
Randomized Controlled TrialA randomised, double-blind, placebo-controlled, efficacy study of nalmefene, as-needed use, in patients with alcohol dependence.
This study evaluated the efficacy of as-needed use of the opioid system modulator nalmefene in reducing alcohol consumption in patients with alcohol dependence. Seven hundred and eighteen patients (placebo=360; nalmefene=358), ≥ 18 years of age, with a diagnosis of alcohol dependence, ≥ 6 heavy drinking days and an average alcohol consumption ≥ WHO medium drinking risk level in the 4 weeks preceding screening, were randomised (1:1) to 24 weeks of as-needed placebo or nalmefene 18 mg/day. The co- primary efficacy analyses showed a significantly superior effect of nalmefene compared to placebo in the change from baseline to month 6 in heavy drinking days (group difference: -1.7 days/month [95% CI -3.1; -0.4]; p=0.012) and a better but not significant effect in reducing total alcohol consumption (group difference: -5.0 g/day last month [95% CI -10.6; 0.7]; p=0.088). ⋯ Improvements in Clinical Global Impression and reductions in liver enzymes were greater in the nalmefene group than in the placebo group. Adverse events were more common with nalmefene; the incidence of adverse events leading to dropout was similar in both groups. This study provides evidence for the efficacy of nalmefene, which constitutes a new pharmacological treatment paradigm in terms of treatment goal (reduced drinking) and dosing regimen (as-needed), in alcohol dependent patients unable to reduce alcohol consumption on their own.
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Eur Neuropsychopharmacol · Nov 2013
Comparative Study Controlled Clinical TrialComparable seizure characteristics in magnetic seizure therapy and electroconvulsive therapy for major depression.
Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression (TRD); however, its use for less severe forms of depression is somewhat limited by a lack of control over current spreading to medial temporal lobe memory structures, resulting in various cognitive side effects. In contrast, magnetic seizure therapy (MST), which uses high frequency repetitive transcranial magnetic stimulation (rTMS) for local seizure induction, has been associated with reduced cognitive side effects. To assess whether different characteristics of seizures induced by both methods are responsible for the differences in neuropsychological side-effect profile, we studied seven TRD-patients undergoing both MST and ECT in an open-label, within subject, controlled crossover pilot study. ⋯ Our results showed no differences in motor activity or EMG and EEG characteristics, thus implicating similar electrophysiological processes in seizure induction with MST and ECT. In line with previous studies, we observed shorter postictal recovery and reorientation times following MST. The ictal characteristics of induced seizures were found similar with ECT and MST suggesting that the more focal seizure induction associated with MST may account for the more beneficial neuropsychological side effect profile of MST.
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Eur Neuropsychopharmacol · Oct 2013
Vulnerability versus resilience to prenatal stress in male and female rats; implications from gene expression profiles in the hippocampus and frontal cortex.
Adverse life events during pregnancy may impact upon the developing fetus, predisposing prenatally stressed offspring to the development of psychopathology. In the present study, we examined the effects of prenatal restraint stress (PS) on anxiety- and depression-related behavior in both male and female adult Sprague-Dawley rats. In addition, gene expression profiles within the hippocampus and frontal cortex (FC) were examined in order to gain more insight into the molecular mechanisms that mediate the behavioral effects of PS exposure. ⋯ Further, the data indicated that epigenetic regulation is affected differentially in male and female PS offspring. These sex-specific alterations may, at least in part, explain the behavioral differences observed between both sexes, i.e. relative vulnerability versus resilience to PS in male versus female rats, respectively. These data reveal novel potential targets for antidepressant and mood stabilizing drug treatments including PDE inhibitors and histone deacetylase (HDAC) inhibitors.
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Eur Neuropsychopharmacol · Oct 2013
Footshock-induced responses in ventral subiculum neurons are mediated by locus coeruleus noradrenergic afferents.
The ventral subiculum (vSub) of the hippocampus is critically involved in mediating the forebrain's response to stress, particularly with regard to psychogenic stressors. Stress, in turn, is known to aggravate many psychiatric conditions including schizophrenia, depression, anxiety, and drug abuse. Pathological alterations in hippocampal function have been identified in all these disorders; thus, it is of interest to understand how stress affects this brain region. ⋯ These results suggest that the LC NE system plays an important role in mediating stress responses in the vSub. Footshock evokes both inhibition and excitation in the vSub, by activating noradrenergic inputs from the LC. These responses may contribute to stress adaptation; while an imbalance of this system may lead to pathological stress responses in mental disorders.
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Eur Neuropsychopharmacol · Oct 2013
Three-way interaction effect of 5-HTTLPR, BDNF Val66Met, and childhood adversity on depression: a replication study.
Both the serotonin transporter linked promoter region (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms have been shown to interact with unfavourable environment in relation to depression symptoms and to depression diagnosis. Several attempts have been made to study a three-way interaction effect of these factors on depression, however with contradictory results. We aimed to test the hypothesis of a three-way interaction effect and to attempt at replication in an independent population-based sample. ⋯ This three-way effect was more pronounced among girls. The current study, with a virtually similar set-up compared to previous studies, can partially confirm previous findings and their generalizability. The study also shows the importance of genetic plasticity in individuals with different environmental exposure, for different phenotypic expression.