The international journal of neuropsychopharmacology
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Int. J. Neuropsychopharmacol. · Jun 2012
Comparative StudyAcute administration of typical and atypical antipsychotics reduces EEG γ power, but only the preclinical compound LY379268 reduces the ketamine-induced rise in γ power.
A single non-anaesthetic dose of ketamine, a non-competitive NMDA receptor (NMDAR) antagonist with hallucinogenic properties, induces cognitive impairment and psychosis, and aggravates schizophrenia symptoms in patients. In conscious rats an equivalent dose of ketamine induces key features of animal models of acute psychosis, including hyperlocomotor activity, deficits in prepulse inhibition and gating of auditory evoked potentials, and concomitantly increases the power of ongoing spontaneously occurring gamma (30-80 Hz) oscillations in the neocortex. This study investigated whether NMDAR antagonist-induced aberrant gamma oscillations could be modulated by acute treatment with typical and atypical antipsychotic drugs. ⋯ All three drugs significantly reduced the power of baseline EEG gamma oscillations by 30-50%, an effect most prominent after LY379268, and all inhibited ketamine-induced hyperlocomotor activity. However, only pretreatment with LY379268 attenuated trough-to-peak ketamine-induced gamma hyperactivity. These results demonstrate that typical and atypical antipsychotic drugs acutely reduce cortical gamma oscillations, an effect that may be related to their clinical efficacy.
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Int. J. Neuropsychopharmacol. · Apr 2012
Review Meta AnalysisEfficacy of agomelatine in major depressive disorder: meta-analysis and appraisal.
Agomelatine is the first approved antidepressant that mediates its activity through the melatoninergic pathway rather than the monoaminergic system. This meta-analysis aims to summarize an up-to-date report on the efficacy of agomelatine in major depressive disorder. Archives of published results in PubMed, CINAHL, Cochrane Library, EMBASE and PsycINFO databases were searched for randomized double-blind trials comparing agomelatine against placebo or antidepressant in major depressive disorder. ⋯ There were nine trials involving 3943 severe cases of depression on agomelatine (n=2390) and either placebo (n=689) or antidepressants (n=864). Agomelatine (n=1274) stood superior to placebo (n=689) by a small margin (SMD -0.26, p=3.48×10-11) and the superiority of agomelatine (n=834, dose ≥ 25 mg/d) over antidepressants (paroxetine, fluoxetine, sertraline, venlafaxine; n=864) was even smaller (SMD -0.11, p=0.02). Although there is evidence of the superiority of agomelatine over placebo and selected antidepressants, it is questionable whether the magnitude of effect size is clinically significant and sample characteristics are relevant to the general patient population with major depressive disorder.
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Int. J. Neuropsychopharmacol. · Apr 2012
Serotonin-2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect of acute imipramine and fluoxetine administration.
A growing body of evidence indicates that facilitation of serotonin-2C receptor (5-HT2CR)-mediated neurotransmission in the basolateral nucleus of the amygdala (BLA) is involved in anxiety generation. We investigated here whether BLA 5-HT2CRs exert a differential role in the regulation of defensive behaviours related to generalized anxiety (inhibitory avoidance) and panic (escape) disorders. We also evaluated whether activation of BLA 5-HT2CRs accounts for the anxiogenic effect caused by acute systemic administration of the antidepressants imipramine and fluoxetine. ⋯ Intra-BLA injection of a sub-effective dose of SB-242084 fully blocked the anxiogenic effect caused either by the local microinjection of 5-HT or the systemic administration of imipramine and fluoxetine. Our findings indicate that 5-HT2CRs in BLA are selectively involved in the regulation of defensive behaviours associated with generalized anxiety, but not panic. The results also provide the first direct evidence that activation of BLA 5-HT2CRs accounts for the short-term aversive effect of antidepressants.
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Int. J. Neuropsychopharmacol. · Feb 2012
Randomized Controlled TrialA randomized trial of paliperidone palmitate and risperidone long-acting injectable in schizophrenia.
Paliperidone palmitate (PP) is a recently (USA) approved injectable new-generation antipsychotic. This 53-wk, Phase-III double-blind study was designed to assess the non-inferiority of PP to risperidone long-acting injectable (RIS-LAI) in schizophrenia treatment. Acutely symptomatic patients (n=749), with a Positive and Negative Syndrome Scale (PANSS) total score between 60 and 120 were randomly allocated to gluteal injections of either (a) PP: 50 mg eq. on days 1 and 8, and flexible dosing [25-100 mg eq. (i.e. 39-156 mg USA dosing)] once-monthly; or (b) RIS-LAI: bi-weekly injections of 25 mg on days 8 and 22, and flexible dosing (25-50 mg) starting from day 36, with allowed oral supplementation. ⋯ Insomnia was the most common treatment-emergent adverse event, with a similar incidence in both groups (15%). PP did not demonstrate comparable efficacy to RIS-LAI, which may be attributable to the initiation dosing strategy employed. Tolerability of both treatments was comparable to previous studies, with no new safety signals detected.
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Int. J. Neuropsychopharmacol. · Nov 2011
Randomized Controlled TrialEvidence for involvement of the insula in the psychotropic effects of THC in humans: a double-blind, randomized pharmacological MRI study.
The main reason for recreational use of cannabis is the 'high', the primary psychotropic effect of Δ9-tetrahydrocannabinol (THC). This psychoactive compound of cannabis induces a range of subjective, physical and mental reactions. The effect on heart rate is pronounced and complicates bloodflow-based neuroimaging of psychotropic effects of THC. ⋯ In conclusion, an acute THC challenge altered baseline brain perfusion and activity, especially in frontal brain areas involved in cognitive and emotional processes, and the insula, associated with interoceptive awareness. These changes may represent the THC-induced neurophysiological correlates of feeling high. The alterations in baseline brain perfusion and activity also have relevance for studies on task-related effects of THC on brain function.