Psychopharmacology
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Review Meta Analysis
Ketamine administration in depressive disorders: a systematic review and meta-analysis.
Ketamine's efficacy in depressive disorders has been established in several controlled trials. The aim of the present study was to determine whether or not ketamine administration significantly improves depressive symptomatology in depression and more specifically in major depressive disorder (MDD), bipolar depression, resistant depression (non-ECT studies), and as an anesthetic agent in electroconvulsive therapy (ECT) for resistant depression (ECT studies). Secondary outcomes were the duration of ketamine's effect, the efficacy on suicidal ideations, the existence of a dose effect, and the safety/tolerance of the treatment. ⋯ The present meta-analysis confirms ketamine's efficacy in depressive disorders in non-ECT studies, as well as in ECT studies. The results of this first meta-analysis are encouraging, and further studies are warranted to detail efficacy in bipolar disorders and other specific depressed populations. Middle- and long-term efficacy and safety have yet to be explored. Extrapolation should be cautious: Patients included had no history of psychotic episodes and no history of alcohol or substance use disorders, which is not representative of all the depressed patients that may benefit from this therapy.
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Gamma-aminobutyric acid type A receptors (GABAARs) are the principal mediators of inhibitory transmission in the mammalian central nervous system. GABAARs can be localized at post-synaptic inhibitory specializations or at extrasynaptic sites. While synaptic GABAARs are activated transiently following the release of GABA from presynaptic vesicles, extrasynaptic GABAARs are typically activated continuously by ambient GABA concentrations and thus mediate tonic inhibition. The tonic inhibitory currents mediated by extrasynaptic GABAARs control neuronal excitability and the strength of synaptic transmission. However, the mechanisms by which neurons control the functional properties of extrasynaptic GABAARs had not yet been explored. ⋯ Trafficking and stability of functional channels to the membrane surface are critical for inhibitory efficacy. Phosphorylation of residues within GABAAR subunits plays an essential role in the assembly, trafficking, and cell surface stability of GABAARs. Neurosteroids are produced in the brain and are highly efficacious allosteric modulators of GABAAR-mediated current. This allosteric modulation by neurosteroids is influenced by the phosphorylated state of the GABAAR which is subunit dependent, adding temporal and regional variability to the neurosteroid response. Possible links between neurosteroid actions, phosphorylation, and GABAAR trafficking remain to be explored, but potential novel therapeutic targets may exist for numerous neurological and psychological disorders which are linked to fluctuations in neurosteroid levels and GABAA subunit expression.
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Dysregulated reward processing is a hallmark feature of drug addiction; however, scant research has evaluated restructuring reward processing in the context of addiction treatment. ⋯ Results suggest that during treatment with MORE, cardiac-autonomic responsiveness to non-drug reward increases, while reactivity to opioid reward decreases. Studies are needed to discern whether changes in RR were a result or a determinant of reductions in opioid misuse and craving. RR may play a role in addiction treatment.
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Comparative Study
Mechanism of action of the bimodal antidepressant vilazodone: evidence for serotonin1A-receptor-mediated auto-augmentation of extracellular serotonin output.
The recently approved antidepressant vilazodone, a serotonin (5-HT)1A receptor partial agonist/selective 5-HT reuptake inhibitor offers new possibilities to study the underlying mechanisms of depression pharmacotherapy and of 5-HT augmenting antidepressants. ⋯ In spite of high intrinsic 5-HT1A activity in reserpinized rats, the net effect of vilazodone at release-regulating 5-HT1A autoreceptors must be inhibitory, leading to markedly increased 5-HT output. Another possibility is that vilazodone rapidly desensitizes autoinhibitory 5-HT1A receptors by an unknown mechanism.
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Chronic amphetamine treatment reduces cocaine self-administration in pre-clinical and clinical settings, and amphetamine has been proposed as a candidate medication for treatment of cocaine abuse. ⋯ These data suggest that chronic amphetamine treatment blunts expression of abuse-related cocaine effects on ICSS in rats.