martes, 16 de enero de 2018

Ketamina en depresión mayor / Ketamina for major depression

Enero 16, 2018. No. 2965

Con este tercer envío consecutivo sobre ketamina en depresión mayor esperamos que hayamos motivado su interés y curiosidad científica sobre este apasionante tema. Hay mucha información disponible y actualizada que con seguridad terminará en la aprobación de este anestésico general como una novel droga antidepresiva de rápido inicio. 

With this third consecutive e-mail on ketamine in major depression, we hope that we have motivated your interest and scientific curiosity on this exciting topic. There is a lot of information available and updated that will surely end in the approval of this general anesthetic as a novel fast-acting antidepressant drug.

Avec cette troisième expédition consécutive sur la kétamine dans la dépression majeure, nous espérons que nous avons motivé votre intérêt et votre curiosité scientifique sur ce sujet passionnant. Il y a beaucoup d'informations disponibles et mises à jour qui finiront sûrement par l'approbation de cette anesthésie générale en tant que nouveau médicament antidépresseur à action rapide.
Disección molecular y celular de subtipos de receptores NMDA como dianas antidepresivas.
Molecular and cellular dissection of NMDA receptor subtypes as antidepressant targets.
Neurosci Biobehav Rev. 2018 Jan;84:352-358. doi: 10.1016/j.neubiorev.2017.08.012. Epub 2017 Aug 23.
Abstract
A growing body of evidence supports the idea that drugs targeting the glutamate system may represent a valuable therapeutic alternative in major depressive disorders (MDD). The rapid and prolonged mood elevating effect of the NMDA receptor (NMDAR) antagonist ketamine has been studied intensely. However, its clinical use is hampered by deleterious side-effects, such as psychosis. Therefore, a better understanding of the mechanisms of the psychotropic effects after NMDAR blockade is necessary to develop glutamatergic antidepressants with improved therapeutic profile. Here we review recent experimental data that addressed molecular/cellular determinants of the antidepressant effect mediated by inactivating NMDAR subtypes. We refer to results obtained both in pharmacological and genetic animal models, ranging from global to conditional NMDAR manipulation. Our main focus is on the contribution of different NMDAR subtypes to the psychoactive effects induced by NMDAR ablation/blockade. We review data analyzing the effect of NMDAR subtype deletions limited to specific neuronal populations/brain areas in the regulation of mood. Altogether, these studies suggest effective and putative specific NMDAR drug targets for MDD treatment.
KEYWORDS: Depression; GluN2 subunits; Glutamate; Ketamine; Molecular biology; NMDA receptors
Uso de terapia repetida con ketamina intravenosa en la depresión bipolar resistente al tratamiento con comportamiento suicida: informe de un caso de España.
Use of repeated intravenous ketamine therapy in treatment-resistant bipolar depression with suicidal behaviour: a case report from Spain.
Ther Adv Psychopharmacol. 2017 Apr;7(4):137-140. doi: 10.1177/2045125316675578. Epub 2017 Jan 1.
Abstract
The rapidly-acting antidepressant properties of ketamine are a trend topic in psychiatry. Despite its robust effects, these are ephemeral and can lead to certain adverse events. For this reason, there is still a general concern around the off-label use of ketamine in clinical practice settings. Nonetheless, for refractory depression, it should be an indication to consider. We report the case of a female patient admitted for several months due to a treatment-resistant depressive bipolar episode with chronic suicidal behaviour. After repeated intravenous ketamine infusions without remarkable side effects, the patient experienced a complete clinical recovery during the 4 weeks following hospital discharge. Unfortunately, depressive symptoms reappeared in the 5th week, and the patient was finally readmitted to hospital as a result of a suicide attempt.
KEYWORDS: antidepressive agents; bipolar disorder; depression; ketamine; suicide
La administración aguda de ketamina corrige los marcadores óseos inflamatorios anormales en el trastorno depresivo mayor.
Acute ketamine administration corrects abnormal inflammatory bone markers in major depressive disorder.
Mol Psychiatry. 2017 May 30. doi: 10.1038/mp.2017.109. [Epub ahead of print]
Abstract
Patients with major depressive disorder (MDD) have clinically relevant, significant decreases in bone mineral density (BMD). We sought to determine if predictive markers of bone inflammation-the osteoprotegerin (OPG)-RANK-RANKL system or osteopontin (OPN)-play a role in the bone abnormalities associated with MDD and, if so, whether ketamine treatment corrected the abnormalities. The OPG-RANK-RANKL system plays the principal role in determining the balance between bone resorption and bone formation. RANKL is the osteoclast differentiating factor and diminishes BMD. OPG is a decoy receptor for RANKL, thereby increasing BMD. OPN is the bone glue that acts as a scaffold between bone tissues matrix composition to bind them together and is an important component of bone strength and fracture resistance. ...
We conclude that the OPG-RANK-RANKL system and the OPN system play important roles in the serious bone abnormalities associated with MDD. These data suggest that, in addition to its antidepressant effects, ketamine also has a salutary effect on a major medical complication of depressive illness. 
Nuevas estrategias de tratamiento de la depresión: basadas en mecanismos relacionados con la neuroplasticidad.
New Treatment Strategies of Depression: Based on Mechanisms Related to Neuroplasticity.
Huang YJ1, Lane HY1,2,3, Lin CH2,4,5.
Neural Plast. 2017;2017:4605971. doi: 10.1155/2017/4605971. Epub 2017 Apr 11.
Abstract
Major depressive disorder is a severe and complex mental disorder. Impaired neurotransmission and disrupted signalling pathways may influence neuroplasticity, which is involved in the brain dysfunction in depression. Traditional neurobiological theories of depression, such as monoamine hypothesis, cannot fully explain the whole picture of depressive disorders. In this review, we discussed new treatment directions of depression, including modulation of glutamatergic system and noninvasive brain stimulation. Dysfunction of glutamatergic neurotransmission plays an important role in the pathophysiology of depression. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has rapid and lasting antidepressive effects in previous studies. In addition to ketamine, other glutamatergic modulators, such as sarcosine, also show potential antidepressant effect in animal models or clinical trials. Noninvasive brain stimulation is another new treatment strategy beyond pharmacotherapy. Growing evidence has demonstrated that superficial brain stimulations, such as transcranial magnetic stimulation, transcranial direct current stimulation, cranial electrotherapy stimulation, and magnetic seizure therapy, can improve depressive symptoms. The antidepressive effect of these brain stimulations may be through modulating neuroplasticity. In conclusion, drugs that modulate neurotransmission via NMDA receptor and noninvasive brain stimulation may provide new directions of treatment for depression. Furthermore, exploring the underlying mechanisms will help in developing novel therapies for depression in the future.
¿ENCENDIDO o APAGADO ?: Modulando el Receptor de N-Metil-D-Aspartato en la Depresión Mayor.
ON or OFF?: Modulating the N-Methyl-D-Aspartate Receptor in Major Depression.
Front Mol Neurosci. 2017 Jan 13;9:169. doi: 10.3389/fnmol.2016.00169. eCollection 2016.
Abstract
Since the discovery that a single dose of ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, had rapid and long-lasting antidepressant effects, there has been increased interest in using NMDAR modulators in the pharmacotherapy of depression. Ketamine's efficacy seems to imply that depression is a disorder of NMDAR hyperfunctionality. However, studies showing that not all NMDAR antagonists are able to act as antidepressants challenge this notion. Furthermore, NMDAR co-agonists have also been gaining attention as possible treatments. Co-agonists such as D-serine and sarcosine have shown efficacy in both pre-clinical models and human trials. This raises the question of how both NMDAR antagonists and agonists are able to have converging behavioral effects. Here we critically review the evidence and proposed therapeutic mechanisms for both NMDAR antagonists and agonists, and collate several theories on how both activation and inhibition of NMDARs appear to have antidepressant effects.
KEYWORDS: NMDAR antagonist; depression; glycine site; mTOR; subuni

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