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Resistant major depression

Wei Guo, Rodrigo Machado-Vieira, Sanjay Mathew, James W Murrough, Dennis S Charney, Matthew Gruenbaum, Maria A Oquendo, Bashkim Kadriu, Nirmala Akula, Ioline Henter, Peixiong Yuan, Kathleen Merikangas, Wayne Drevets, Maura Furey, J John Mann, Francis J McMahon, Carlos A Zarate, Yin Yao Shugart
Growing evidence suggests that the glutamatergic modulator ketamine has rapid antidepressant effects in treatment-resistant depressed subjects. The anticholinergic agent scopolamine has also shown promise as a rapid-acting antidepressant. This study applied genome-wide markers to investigate the role of genetic variants in predicting acute antidepressant response to both agents. The ketamine-treated sample included 157 unrelated European subjects with major depressive disorder (MDD) or bipolar disorder (BD)...
December 14, 2018: Translational Psychiatry
Allison C Nugent, Kathleen E Wills, Jessica R Gilbert, Carlos A Zarate
Preclinical and clinical evidence has demonstrated that ketamine has rapid antidepressant effects. Studies using pre-treatment with an AMPA inhibitor suggest that enhancing AMPA throughput is crucial to ketamine's effects, including increases in both basal and evoked gamma power. This study sought to replicate previous findings of increased gamma response to a somatosensory stimulus at 230 min and Day 1 in ketamine responders versus non-responders in 31 depressed subjects and 25 healthy controls. A significant difference in peak gamma power was seen in the depressed ketamine responders versus non-responders...
September 12, 2018: Psychiatry research. Neuroimaging
Tatsuya Arai, Daichi Fukami, Tamotsu Hoshino, Hidemasa Kondo, Sakae Tsuda
Various microbes, including fungi and bacteria, that live in cold environments produce ice-binding proteins (IBPs) that protect them from freezing. Ascomycota and Basidiomycota are two major phyla of fungi, and Antarctomyces psychrotrophicus is currently designated as the sole ascomycete that produces IBP (AnpIBP). However, its complete amino acid sequence, ice-binding property, and evolutionary history have not yet been clarified. Here, we determined the peptide sequences of three new AnpIBP isoforms by total cDNA analysis and compared them with those of other microbial IBPs...
December 10, 2018: FEBS Journal
John P Andrews, Zongwei Yue, Jun Hwan Ryu, Garrett Neske, David A McCormick, Hal Blumenfeld
Focal limbic seizures often impair consciousness/awareness with major negative impact on quality of life. Recent work has shown that limbic seizures depress brainstem arousal systems, including reduced action potential firing in a key node: cholinergic neurons of the pedunculopontine tegmental nucleus (PPT). In vivo whole-cell recordings have not previously been achieved in PPT, but are used here with the goal of elucidating the mechanisms of reduced PPT cholinergic neuronal activity. An established model of focal limbic seizures was used in rats following brief hippocampal stimulation under light anesthesia...
December 10, 2018: Experimental Neurology
Bende Zou, William S Cao, Zhiwei Guan, Kui Xiao, Conrado Pascual, Julian Xie, Jingxi Zhang, James Xie, Frank Kayser, Craig W Lindsley, C David Weaver, Jidong Fang, Xinmin Simon Xie
Study Objectives: A major challenge in treating insomnia is to find effective medicines with fewer side effects. Activation of G-protein-gated inward rectifying K+ channels (GIRKs) by GABAB agonists baclofen or γ-hydroxybutyric acid (GHB) promotes non-rapid eye movement (NREM) sleep and consolidates sleep. However, baclofen has poor brain penetration, GHB possesses abuse liability, and in rodents both drugs cause spike-wave discharges (SWDs), an absence seizure activity. We tested the hypothesis that direct GIRK activation promotes sleep without inducing SWD using ML297, a potent and selective GIRK activator...
December 11, 2018: Sleep
Ileana Marinescu, Octavian Vasiliu, Daniel Vasile
An intensively researched and yet poorly understood phenomenon, both at clinical and neurobiological level, is the determinism of treatment-resistant depression. Even more controversial are the stages of approaching therapeutically this pathology because there are no evidence-based recommendations stating that a pharmacological agent is superior to another, on medium and long-term. Due to the lack of "golden standard" approaches, physician's experience, therapeutic alliance and a close monitoring stand as the most useful good practices in the treatment of resistant depression...
2018: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
Helge Hasselmann, Stefanie Gamradt, Aline Taenzer, Jan Nowacki, Rami Zain, Kostas Patas, Caren Ramien, Friedemann Paul, Katja Wingenfeld, Dominique Piber, Stefan M Gold, Christian Otte
Several lines of evidence have strongly implicated inflammatory processes in the pathobiology of major depressive disorder (MDD). However, the cellular origin of inflammatory signals and their specificity remain unclear. We examined the phenotype and glucocorticoid signaling in key cell populations of the innate immune system (monocytes) vs. adaptive immunity (T cells) in a sample of 35 well-characterized, antidepressant-free patients with MDD and 35 healthy controls individually matched for age, sex, smoking status and body mass index...
2018: Frontiers in Immunology
Véronique Desbeaumes Jodoin, Jean-Philippe Miron, Paul Lespérance
OBJECTIVE: Major depressive disorder (MDD) is a prevalent condition in older adults. Although antidepressant drugs are commonly prescribed, efficacy is variable, and older patients are more prone to side effects. Repetitive transcranial magnetic stimulation (rTMS) is an alternative therapy used increasingly in the treatment of MDD. Even though recent studies have shown efficacy of rTMS in elderly depressed patients, the safety and efficacy of accelerated rTMS has not been studied in this population...
November 2, 2018: American Journal of Geriatric Psychiatry
Séverine Martin, Romain Colle, Khalil El Asmar, Adrien Rigal, Albane Vievard, Bruno Feve, Laurent Becquemont, Céline Verstuyft, Emmanuelle Corruble
BACKGROUND: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with response to antidepressant drugs in depressed patients and with metabolic side effects after antipsychotic treatment. This study aims to assess the association between this polymorphism and insulin resistance after antidepressant treatment in depressed patients. METHODS: One hundred forty-eight Caucasian patients with a current unipolar major depressive episode (DSM IV-TR) were genotyped for the BDNF Val66Met polymorphism and assessed at baseline and after 3 and 6 months of antidepressant treatment for the 'Homoeostasis model assessment of insulin resistance' (HOMA-IR) index, a valid measure of insulin resistance based on fasting plasma insulinaemia and glycaemia...
December 11, 2018: Psychological Medicine
R H McAllister-Williams, D M B Christmas, A J Cleare, A Currie, J Gledhill, L Insole, A L Malizia, M McGeever, R Morriss, L J Robinson, M Scott, P R A Stokes, P S Talbot, A H Young
SummaryMany novel therapeutic options for depression exist that are either not mentioned in clinical guidelines or recommended only for use in highly specialist services. The challenge faced by clinicians is when it might be appropriate to consider such 'non-standard' interventions. This analysis proposes a framework to aid this decision.Declaration of interestIn the past 3 years R.H.M.W. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending advisory boards) from various pharmaceutical companies including Astra Zeneca, Cyberonics, Eli Lilly, Janssen, LivaNova, Lundbeck, MyTomorrows, Otsuka, Pfizer, Roche, Servier, SPIMACO and Sunovion...
May 2018: British Journal of Psychiatry: the Journal of Mental Science
Srinivas Balachander, Prabhath Gujjadi Kodancha, Shyam Sundar Arumugham, Jaisoorya T Sekharan, Janardhanan C Narayanaswamy, Y C Janardhan Reddy
BACKGROUND: Despite its favorable pharmacological profile and efficacy in major depression and anxiety disorders, evidence for the use of venlafaxine in obsessive-compulsive disorder (OCD) is limited. We sought to examine the real-world effectiveness of venlafaxine from a large database of an OCD clinic in India. METHODS: A total of 1704 consecutive patients who registered at the OCD clinic between June 2014 and December 2016 were evaluated with structured interviews and scales...
December 3, 2018: Journal of Clinical Psychopharmacology
Víctor Navarro, Ilham Boulahfa, Amadeu Obach, Dídac Jerez, Maribel Diaz-Ricart, Cristóbal Gastó, Joana Guarch
PURPOSE/BACKGROUND: Newer-generation antidepressants used in monotherapy or in combination with other newer-generation antidepressants or other psychotropic drugs are usually preferred as first- or second-step treatment options in resistant depression. According to our clinical experience, tricyclic antidepressants still are one of our preferred first choices in treatment-resistant moderate to severe unipolar major depressive episodes. METHODS: This 10-week open-design randomized study assessed the effectiveness of switching to imipramine (adjusted to plasma levels) compared with add-on mirtazapine (30 mg/d) for treatment of moderate to severe unipolar major depressive episodes after a 10-week unsuccessful venlafaxine regimen (225-300 mg/d)...
December 3, 2018: Journal of Clinical Psychopharmacology
Kai Zhang, Kenji Hashimoto
Depression is one of the most disabling diseases worldwide. Approximately one-third of depressed patients are treatment-resistant to the currently available antidepressants and there is a significant therapeutic time lag of weeks to months. There is a clear unmet need for rapid-acting and more efficacious treatments. (R,S)-ketamine, an old anesthetic drug, appears now to be going through a renaissance. Areas covered: This paper reviews recent literature describing the antidepressant effects of ketamine and its enantiomer (S)-ketamine in patients with major depressive disorder (MDD) and bipolar disorder (BD)...
December 4, 2018: Expert Review of Neurotherapeutics
Francesco Angelucci, Bart A Ellenbroek, Aram El Khoury, Aleksander A Mathé
OBJECTIVE: Genetic and environmental factors interact in the development of major depressive disorder (MDD). While neurobiological correlates have only partially been elucidated, altered levels of calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) in animal models and in the cerebrospinal fluid of depressed patients were reported, suggesting that CGRP may be involved in the pathophysiology and/or be a trait marker of MDD. However, changes in CGRP brain levels resulting from interactions between genetic and environmental risk factors and the response to antidepressant treatment have not been explored...
December 4, 2018: Acta Neuropsychiatrica
Jerome C Foo, Fabian Streit, Josef Frank, Stephanie H Witt, Jens Treutlein, Bernhard T Baune, Susanne Moebus, Karl-Heinz Jöckel, Andreas J Forstner, Markus M Nöthen, Marcella Rietschel, Alexander Sartorius, Laura Kranaster
Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistant depression; disorder severity and unfavorable treatment outcomes are shown to be influenced by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment and response/nonresponse are associated with an increased genetic burden for major depression (MD) using polygenic risk score (PRS), which summarize the contribution of disease-related common risk variants. Fifty-one psychiatric inpatients suffering from a major depressive episode underwent ECT...
December 2, 2018: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Takeshi Suzuki, Kazuo Mihara, Goyo Nagai, Shoko Kagawa, Akifumi Nakamura, Kenji Nemoto, Tsuyoshi Kondo
BACKGROUND: In a previous study the authors had shown that in treatment-resistant depressive disorder an early therapeutic response to lamotrigine augmentation therapy is dependent on its plasma concentrations. Lamotrigine is mainly metabolized by UGT1A4 and UGT2B7 and polymorphisms of said UGTs that affect enzyme activities have been reported. The present study investigated the effect of these polymorphisms on the steady-state plasma concentrations (Css) of lamotrigine in patients with treatment-resistant depressive disorder receiving lamotrigine as augmentation therapy...
November 22, 2018: Therapeutic Drug Monitoring
M R Guimarães, A R Soares, A M Cunha, M Esteves, S Borges, R Magalhães, P S Moreira, A J Rodrigues, N Sousa, A Almeida, H Leite-Almeida
Chronic pain is frequently accompanied by the manifestation of emotional disturbances and cognitive deficits. While a causality relation between pain and emotional/cognitive disturbances is generally assumed, several observations suggest a temporal dissociation and independent mechanisms. We therefore studied Sprague-Dawley rats that presented a natural resistance to pain manifestation in a neuropathy model (spared nerve injury; SNI) and compared their performance in a battery of behavioral paradigms - anxiety, depression and fear memory - with animals that presented a pain phenotype...
November 28, 2018: Genes, Brain, and Behavior
Bettadapura N Srikumar, Pattipati S Naidu, Narasimharaju Kalidindi, Mahesh Paschapur, Bharath Adepu, Siva Subramani, Jignesh Nagar, Ratika Srivastava, Muppana V Sreedhara, Durga Shiva Prasad, Manish Lal Das, Justin V Louis, Vijaya K Kuchibhotla, Shailesh Dudhgaonkar, Rick L Pieschl, Yu-Wen Li, Linda J Bristow, Manjunath Ramarao, Reeba K Vikramadithyan
BACKGROUND: A significant proportion of patients suffering from major depression fail to remit following treatment and develop treatment-resistant depression. Developing novel treatments requires animal models with good predictive validity. MRL/lpr mice, an established model of systemic lupus erythematosus, show depression-like behavior. AIMS: We evaluated responses to classical antidepressants, and associated immunological and biochemical changes in MRL/lpr mice...
November 28, 2018: Journal of Psychopharmacology
Noah S Philip, Andrew F Leuchter, Ian A Cook, Joe Massaro, John W Goethe, Linda L Carpenter
BACKGROUND: Synchronized transcranial magnetic stimulation (sTMS) is a new modality to reduce symptoms of major depressive disorder (MDD). sTMS uses rotating neodymium magnets to deliver low-field stimulation matched to the individual alpha frequency (IAF). A previous multisite study showed that sTMS significantly reduced MDD symptoms in the per-protocol sample. To this end, we evaluated clinical features associated with optimal sTMS outcomes. METHODS: Using the per-protocol sample (n = 120) from the parent sham-controlled trial, we performed univariate and stepwise linear regression to identify predictors of response after 6 weeks of sTMS...
November 27, 2018: Depression and Anxiety
Nuri B Farber
Fifteen to thirty percent of patients with major depressive disorder do not respond to antidepressants that target the monoaminergic systems. NMDA antagonists are currently being actively investigated as a treatment for these patients. Ketamine is the most widely studied of the compounds. A brief infusion of a low dose of this agent produces rapid improvement in depressive symptoms that lasts for several days. The improvement occurs after the agent has produced its well characterized psychotomimetic and cognitive side effects...
November 27, 2018: Handbook of Experimental Pharmacology
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