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Resistant major depression

Adam J Walker, J Blair Price, Kristin Borreggine, Shari L Sutor, Andrea Gogos, Jane A McGillivray, Mark A Frye, Susannah J Tye
Lithium has been shown to have some therapeutic efficacy as an adjunctive treatment for intractable forms of major depression. Activation of mammalian target of rapamycin (mTOR) and inhibition of glycogen synthase kinase-3β (GSK3β) have been implicated in its putative mechanisms of action. These proteins are integral components of the insulin signaling pathway, which may serve as a critical co-regulator of drug action. Utilizing an animal model of tricyclic antidepressant resistance, we investigated the relationship between insulin signaling and antidepressant response to lithium augmentation...
March 15, 2019: Translational Psychiatry
Shigeyuki Chaki, Kenichi Fukumoto
Numerous studies have demonstrated the antidepressant effects of group II metabotropic glutamate (mGlu2/3) receptor antagonists in various rodent models. Importantly, it has been shown that the antidepressant effects of mGlu2/3 receptor antagonists in rodent models are similar to those of ketamine, which exerts rapid and long-lasting antidepressant effects in patients with major depressive disorders, including patients with treatment-resistant depression. In addition, the synaptic mechanisms underlying the effects of mGlu2/3 receptor antagonists are reported to be similar to those underlying the effects of ketamine...
March 13, 2019: International Journal of Molecular Sciences
Volker A Coenen, Bettina H Bewernick, Sarah Kayser, Hannah Kilian, Jan Boström, Susanne Greschus, René Hurlemann, Margaretha Eva Klein, Susanne Spanier, Bastian Sajonz, Horst Urbach, Thomas E Schlaepfer
Short- and long-term antidepressant effects of deep brain stimulation (DBS) in treatment-resistant depression (TRD) have been demonstrated for several brain targets in open-label studies. For two stimulation targets, pivotal randomized trials have been conducted; both failed a futility analysis. We assessed efficacy and safety of DBS of the supero-lateral branch of the medial forebrain bundle (slMFB) in a small Phase I clinical study with a randomized-controlled onset of stimulation in order to obtain data for the planning of a large RCT...
March 13, 2019: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Sitwat Malik, Azfar Malik, Kimberly Mercille
Background and ObjectiveResearch suggests that repetitive Transcranial Magnetic Stimulation (rTMS) is effective, safe, and proven treatment option for patients with treatment resistant major depressive disorder (MDD). Success rate is high, around 65-70% nationwide. Around 30% patients are still not responding to the treatment. Objective of this study is to evaluate the cause of treatment failure or non-responsiveness of TMS treatment despite high efficacy of the therapy. This is the first study to evaluate the cause of treatment failure of TMS therapy...
February 2019: CNS Spectrums
Mengyang Feng, Nicole A Crowley, Akshilkumar Patel, Yao Guo, Sierra E Bugni, Bernhard Luscher
Neuroinflammation is associated with increased vulnerability to diverse psychiatric conditions, including treatment-resistant major depressive disorder (MDD). Here we assessed whether high fat diet (HFD) induced neuroinflammation may be suitable to model a treatment-resistant depressive-like brain state in mice. Male and female mice were fed a HFD for 18 weeks, followed by quantitation of glucose tolerance, inflammatory markers of brain tissue (TNFα, IL-6, IL-1β, Iba-1), neural excitability in the prelimbic cortex (PLC), as well as assessment of emotional reactivity and hedonic behavior in a battery of behavioral tests...
March 8, 2019: Neuroscience
Alisson Paulino Trevizol, Kyle W Goldberger, Benoit H Mulsant, Tarek K Rajji, Jonathan Downar, Zafiris J Daskalakis, Daniel M Blumberger
BACKGROUND: The management of late-life depression is challenged by high rates of treatment-resistance and adverse effects, along with medical comorbidities and polypharmacy. Together with the limited data on managing treatment-resistant depression in older adults, there is a need for investigating the efficacy of non-pharmacological treatment strategies. Repetitive transcranial magnetic stimulation (rTMS) is one modality that may better serve this patient population. METHODS: The present study examines data from two previous clinical trials (NCT00305045 and NCT01515215) to explore the efficacy of bilateral and unilateral high-frequency left-sided (HFL) rTMS in older adults suffering from treatment-resistant depression...
March 10, 2019: International Journal of Geriatric Psychiatry
Thu Ha Pham, Alain M Gardier
Ketamine, a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptor, displays a fast antidepressant activity in treatment-resistant depression and in rodent models of anxiety/depression. A large body of evidence concerning the cellular and molecular mechanisms underlying its fast antidepressant-like activity comes from animal studies. Although structural remodeling of frontocortical/hippocampal neurons has been proposed as critical, the role of excitatory/inhibitory neurotransmitters in this behavioral effect is unclear...
March 6, 2019: Pharmacology & Therapeutics
A Murru, G Guiso, M Barbuti, G Anmella, N Verdolini, L Samalin, J M Azorin, J Jules Angst, C L Bowden, S Mosolov, A H Young, D Popovic, M Valdes, G Perugi, E Vieta, I Pacchiarotti
According to the DSM-5, "reduction in the need for sleep" is the only sleep-related criteria for mixed features in depressive episodes. We aimed at studying the prevalence, clinical correlates and the role of hypersomnia in a sample of acutely depressed patients. Secondarily, we factors significantly increasing the odds of hypersomnia were studied. We conducted a post-hoc analysis of the BRIDGE-II-Mix study. Variables were compared between patients with hypersomnia (SLEEP+) and with insomnia (SLEEP-) with standard bivariate tests...
March 4, 2019: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
K K Shahedah, S H How, A R Jamalludin, M T Mohd Faiz, Y C Kuan, C K Ong
BACKGROUND: Depression is a recognized complication of lung cancer underreported in developing countries such as Malaysia. Treating and identifying depression in cancer patients increases survival and quality of life. Our objectives are to study prevalence of depressive symptoms in newly diagnosed lung carcinoma, and examine the relationship of depressive symptoms with other influencing risk factors. METHODS: A 2-year, cross sectional study February 2015-February 2017, was conducted at Hospital Tengku Ampuan Afzan, and Penang General Hospital...
December 20, 2018: Tuberculosis and Respiratory Diseases
Natalia de M Lyra E Silva, Minh P Lam, Claudio N Soares, Douglas P Munoz, Roumen Milev, Fernanda G De Felice
Neuropsychiatric disorders and type 2 diabetes (T2D) are major public health concerns proposed to be intimately connected. T2D is associated with increased risk of dementia, neuropsychiatric and mood disorders. Evidences of the involvement of insulin signaling on brain mechanisms related to depression indicate that insulin resistance, a hallmark of type 2 diabetes, could develop in the brains of depressive patients. In this article, we briefly review possible molecular mechanisms associating defective brain insulin signaling with reward system, neurogenesis, synaptic plasticity and hypothalamic-pituitary-adrenal (HPA) stress axis in depression...
2019: Frontiers in Psychiatry
Marin Veldic, Ahmed T Ahmed, Caren J Blacker, Jennifer R Geske, Joanna M Biernacka, Kristin L Borreggine, Katherine M Moore, Miguel L Prieto, Jennifer L Vande Voort, Paul E Croarkin, Astrid A Hoberg, Simon Kung, Renato D Alarcon, Nicola Keeth, Balwinder Singh, William V Bobo, Mark A Frye
Background: Pharmacogenomic testing, specifically for pharmacokinetic (PK) and pharmacodynamic (PD) genetic variation, may contribute to a better understanding of baseline genetic differences in patients seeking treatment for depression, which may further impact clinical antidepressant treatment recommendations. This study evaluated PK and PD genetic variation and the clinical use of such testing in treatment seeking patients with bipolar disorder (BP) and major depressive disorder (MDD) and history of multiple drug failures/treatment resistance...
2019: Frontiers in Pharmacology
Jessica L Reed, Allison C Nugent, Maura L Furey, Joanna E Szczepanik, Jennifer W Evans, Carlos A Zarate
BACKGROUND: In the search for novel treatments for depression, ketamine has emerged as a unique agent with rapid antidepressant effects. Experimental tasks involving emotional processing can be used during functional magnetic resonance imaging scanning to investigate ketamine's effects on brain function in major depressive disorder (MDD). This study examined ketamine's effects on functional magnetic resonance imaging activity during an emotional processing task. METHODS: A total of 33 individuals with treatment-resistant MDD and 24 healthy control participants (HCs) took part in this double-blind, placebo-controlled crossover study...
January 25, 2019: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Vivian Naidoo, Sipho Mdanda, Sphamandla Ntshangase, Tricia Naicker, Hendrik G Kruger, Thavendran Govender, Panjasaram Naidoo, Sooraj Baijnath
Ketamine is approved by the FDA to be used as an anesthetic however, recent reports have exhibited its success in the treatment of major depressive disorder (MDD). Studies have suggested that a sub-anesthetic dose produces rapid antidepressant activity providing significant symptomatic relief particularly in patients with a history of treatment resistant depression (TRD). Many reports have been published on the intranasal (IN) efficacy of ketamine in the treatment of depression, however studies that have investigated the effects of the route of administration on drug delivery to the brain appear to be absent in literature...
February 20, 2019: Journal of Psychiatric Research
S C Kaliora, I M Zervas, G N Papadimitriou
Electroconvulsive therapy (ECT) is the oldest among the early biological treatments introduced in psychiatry, and the only one still in use. In this paper we attempt a brief presentation of ECT usage over the last 80 years, since it was originally introduced. It is a safe, well-tolerated, and highly effective treatment option for major psychiatric disorders, such as mood disorders and schizophrenia, especially when there is an acute exacerbation of psychotic symptoms or if catatonic symptoms are prominent. ECT has also been used successfully for the treatment of Parkinson's disease, delirium, neuroleptic malignant syndrome, autism and agitation and depression in demented patients...
October 2018: Psychiatrikē, Psychiatriki
Jeffrey R Strawn, Jeffrey A Mills, Paul E Croarkin
OBJECTIVE: To guide clinicians in selecting the "next line" selective serotonin reuptake inhibitor (SSRI) for adolescents with treatment-resistant major depressive disorder, we sought to compare response rates among SSRIs in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study and to jointly model tolerability and efficacy for the specific SSRI comparisons. METHODS: Efficacy and tolerability data for paroxetine, citalopram, and fluoxetine were extracted from the TORDIA study...
February 27, 2019: Journal of Child and Adolescent Psychopharmacology
Olaitan J Jeremiah, Gráinne Cousins, Finbarr P Leacy, Brian P Kirby, Benedict K Ryan
BACKGROUND: Depression is the leading cause of disability worldwide and is known to be associated with insulin resistance (IR). Insulin resistance worsens the symptoms of depression and reduces the effectiveness of antidepressant medications in some depressed patients. Many studies have assessed the effect of adjunctive exercise, vitamin D supplementation, zinc supplementation, magnesium, probiotics, unsaturated fatty acids, and hygienic-dietary recommendations (sleep hygiene, healthy diet, physical activity, and sunlight exposure, combined or singly used), individually, on antidepressant treatment response...
February 25, 2019: Systematic Reviews
Konstantin A Demin, Maxim Sysoev, Maria V Chernysh, Anna K Savva, Mamiko Koshiba, Edina A Wappler-Guzzetta, Cai Song, Murilo S De Abreu, Brian Leonard, Matthew O Parker, Brian H Harvey, Li Tian, Eero Vasar, Tatyana Strekalova, Tamara G Amstislavskaya, Andrey D Volgin, Erik T Alpyshov, Dongmei Wang, Allan V Kalueff
Depression is a highly debilitating psychiatric disorder that affects the global population and causes severe disabilities and suicide. Depression pathogenesis remains poorly understood, and the disorder is often treatment-resistant and recurrent, necessitating the development of novel therapies, models and concepts in this field. Areas covered: Animal models are indispensable for translational biological psychiatry, and markedly advance the study of depression. Novel approaches continuously emerge that may help untangle the disorder heterogeneity and unclear categories of disease classification systems...
February 22, 2019: Expert Opinion on Drug Discovery
G G H van der Linden, M W H Lochmann van Bennekom, J Spijker
Studies have indicated an association between treatment refractoriness in unipolar depression and unrecognised bipolar spectrum disorder (bsd). If confirmed, this may have implications for diagnosis and treatment.<br/> AIM: To provide an overview on the prevalence and recognition of bsd in treatment resistant depression (trd).<br/> METHOD: A search was made in PubMed concerning the prevalence of bsd in trd and clinical features that may be suggestive of bipolar depression.<br/> RESULTS: Three articles were found that examined the prevalence of bsd in trd; they reported that 26-47% of patients with trd had an underlying bsd...
2019: Tijdschrift Voor Psychiatrie
Karen Caeyenberghs, Romain Duprat, Alexander Leemans, Hadi Hosseini, Peter H Wilson, Debby Klooster, Chris Baeken
Accelerated intermittent theta burst stimulation (aiTBS) is a noninvasive neurostimulation technique that shows promise for improving clinical outcome in patients suffering from treatment-resistant depression (TRD). Although it has been suggested that aiTBS may evoke beneficial neuroplasticity effects in neuronal circuits, the effects of aiTBS on brain networks have not been investigated until now. Fifty TRD patients were enrolled in a randomized double-blind sham-controlled crossover trial involving aiTBS, applied to the left dorsolateral prefrontal cortex...
2019: Network Neuroscience
Kevin Chopra, Jasmin L Katz, Lena C Quilty, Stephen Matthews, Arun Ravindran, Robert D Levitan
BACKGROUND: Chronic Major Depressive Disorder (CMDD) is a common, disabling illness that is often complicated by high reactivity to social stress. To further elucidate the nature of this reactivity, the current study evaluated whether the personality dimensions of neuroticism and extraversion influenced cortisol responses to a social challenge in CMDD patients vs. controls. METHODS: Fifty participants with CMDD and 58 healthy controls completed the Trier Social Stress Test (TSST) using a standard protocol...
February 8, 2019: Psychoneuroendocrinology
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