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Drug resistant depression

Aline Iannone, Antonio Pedro de Mello Cruz, Joaquim Pereira Brasil-Neto, Raphael Boechat-Barros
Transcranial magnetic stimulation (TMS) has recently been investigated as a possible adjuvant treatment for many neuropsychiatric disorders, and has already been approved for the treatment of drug-resistant depression in the United States and in Brazil, among other countries. Although its use in other neuropsychiatric disorders is still largely experimental, many physicians have been using it as an off-label add-on therapy for various disorders. More recently, another technique, transcranial direct current stimulation (tDCS), has also become available as a much cheaper and portable alternative to TMS, although its mechanisms of action are different from those of TMS...
October 2016: Arquivos de Neuro-psiquiatria
Mariusz Papp, Piotr Gruca, Magdalena Lason-Tyburkiewicz, Paul Willner
Ketamine is the prototype of a new generation of antidepressant drugs, which is reported in clinical studies to be effective in treatment-resistant patients, with an effect that appears within hours and lasts for a few days. Chronic mild stress (CMS) is a well-established and widely used animal model of depression, in which anhedonia, anxiogenesis and cognitive dysfunction can be observed reliably. Studies using acute or brief ketamine treatment following withdrawal from CMS have replicated the clinical finding of a rapid onset of antidepressant action...
October 18, 2016: Behavioural Pharmacology
Giulio Perugi, Pierpaolo Medd, Pierpaolo Medd, Cristina Toni, Michela Giorgi Mariani, Chiara Socci, Mauro Mauri
OBJECTIVE: We evaluated the effectiveness of Electroconvulsive Therapy (ECT) in the treatment of Bipolar Disorder (BD) in a large sample of bipolar patients with drug resistant depression, mania, mixed state and catatonic features. METHOD: 522 consecutive patients with DSM-IV-TR BD were evaluated prior to and after the ECT course. Responders and nonresponders were compared in subsamples of depressed and mixed patients. Descriptive analyses were reported for patients with mania and with catatonic features...
October 17, 2016: Current Neuropharmacology
Kohji Shirai
BACKGROUND: The cardio-ankle vascular index (CAVI) is a new arterial stiffness index of the arterial tree from the origin of the aorta to the ankle, and was essentially derived from the stiffness parameterβtheory proposed by Hayashi. The conspicuous feature of CAVI is independency from blood pressure at the time of measurement. AIM: The purpose is to clarify the meaning of CAVI as a surrogate marker of arteriosclerosis, and also the role of CAVI in the blood pressure control system...
September 2016: Journal of Hypertension
N Kappelmann, G Lewis, R Dantzer, P B Jones, G M Khandaker
Inflammatory cytokines are commonly elevated in acute depression and are associated with resistance to monoaminergic treatment. To examine the potential role of cytokines in the pathogenesis and treatment of depression, we carried out a systematic review and meta-analysis of antidepressant activity of anti-cytokine treatment using clinical trials of chronic inflammatory conditions where depressive symptoms were measured as a secondary outcome. Systematic search of the PubMed, EMBASE, PsycINFO and Cochrane databases, search of reference lists and conference abstracts, followed by study selection process yielded 20 clinical trials...
October 18, 2016: Molecular Psychiatry
Madeleine M Uys, Mohammed Shahid, Jukka Sallinen, Brian H Harvey
Depression involves deficits in monoaminergic neurotransmission. Differential roles for α2A, B and C subtypes of the α2-adrenoceptor (AR) are evident, with selective α2C-AR antagonists purported to have antidepressant and procognitive properties. However, this has not been demonstrated in a genetic animal model of depression. The role of the α2C-AR in modulating two key depression-related behaviours in the Flinders Sensitive Line (FSL) rat was studied using a dose-response analysis following subcutaneous administration with the selective α2C-AR antagonist ORM-10921 (0...
September 30, 2016: Behavioural Pharmacology
Danielle Macedo, Adriano José Maia Chaves Filho, Caren Nádia Soares de Sousa, João Quevedo, Tatiana Barichello, Hélio Vitoriano Nobre Júnior, David Freitas de Lucena
OBJECTIVES: The first drug repurposed for the treatment of depression was the tuberculostatic iproniazid. At present, drugs belonging to new classes of antidepressants still have antimicrobial effects. Dysbiosis of gut microbiota was implicated in the development or exacerbation of mental disorders, such as major depressive disorder (MDD). Based on the current interest in the gut-brain axis, the focus of this narrative review is to compile the available studies regarding the influences of gut microbiota in behavior and depression and to show the antimicrobial effect of antidepressant drugs...
September 28, 2016: Journal of Affective Disorders
R Krysiak, A Drosdzol-Cop, V Skrzypulec-Plinta, B Okopień
Aim:Metformin is a drug of choice for the management of type 2 diabetes mellitus. Very little is known about its effect on human sexual function. Methods: The study included 3 age- and weight-matched groups of premenopausal women: individuals with type 2 diabetes, women with prediabetes and healthy controls. All women with diabetes and 50% of those with prediabetes were then treated with metformin and complied with lifestyle modification. The remaining individuals, not receiving pharmacotherapy, only complied with dietary recommendations...
October 6, 2016: Experimental and Clinical Endocrinology & Diabetes
Jacob P R Jacobsen, Andrew D Krystal, K Ranga R Krishnan, Marc G Caron
Serotonin transporter (SERT) inhibitors treat depression by elevating brain extracellular 5-hydroxytryptamine (5-HTExt). However, only one-third of patients respond adequately. Treatment-resistant depression (TRD) is a major unmet need. Interestingly, elevating 5-HTExt beyond what is achieved by a SERT inhibitor appears to treat TRD. Adjunctive administration of 5-hydroxytryptophan (5-HTP) safely elevates 5-HTExt beyond the SERT inhibitor effect in humans; however, 5-HTP cannot be a clinically viable drug because of its poor pharmacokinetics...
September 28, 2016: Trends in Pharmacological Sciences
Anindya Bhattacharya, Wayne C Drevets
Mood disorders are associated with persistently high rates of morbidity and mortality, despite the widespread availability of antidepressant treatments. One limitation to extant therapeutic options has been that nearly all approved antidepressant pharmacotherapies exert a similar primary action of blocking monoamine transporters, and few options exist for transitioning treatment resistant patients to alternatives with distinct mechanisms. An emerging area of science that promises novel pathways to antidepressant and mood-stabilizing therapies has followed from evidence that immunological factors play major roles in the pathophysiology of at least some mood disorder subtypes...
September 28, 2016: Current Topics in Behavioral Neurosciences
Bodo C Melnik
Isotretinoin (13-cis retinoic acid) is the most effective sebum-suppressive drug for the treatment of severe acne. Its effect depends on sebocyte apoptosis, which results from isotretinoin-induced expression of the apoptotic protein tumour necrosis factor-related apoptosis-inducing ligand, insulin-like growth factor-binding protein-3 and neutrophil gelatinase-associated lipocalin. This review proposes that the pharmacological mode of action of isotretinoin in the treatment of severe acne, acute promyelocytic leukaemia, and neuroblastoma results from apoptosis...
September 27, 2016: Acta Dermato-venereologica
P A Geoffroy, J-A Micoulaud Franchi, R Lopez, I Poirot, A Brion, S Royant-Parola, B Etain
OBJECTIVES: Sleep complaints are very common in bipolar disorders (BD) both during acute phases (manic and depressive episodes) and remission (about 80 % of patients with remitted BD have poor sleep quality). Sleep complaints during remission are of particular importance since they are associated with more mood relapses and worse outcomes. In this context, this review discusses the characterization and treatment of sleep complaints in BD. METHODS: We examined the international scientific literature in June 2016 and performed a literature search with PubMed electronic database using the following headings: "bipolar disorder" and ("sleep" or "insomnia" or "hypersomnia" or "circadian" or "apnoea" or "apnea" or "restless legs")...
September 23, 2016: L'Encéphale
Roberto Truzoli, Cecilia Rovetta, Caterina Viganò, Paola Marianna Marinaccio, Gabriella Ba, Phil Reed
BACKGROUND: Drug-resistance for depression and anxiety is a major limitation in the treatment of these common disorders, and adjunct support interventions may be beneficial in the treatment of these patients. AIMS: The purpose of this study was to evaluate the effects of a short-term (8 session) Relaxation Response Skills Training (RRST) programme for a population of psychiatric outpatients with anxiety and mood disorders who were unresponsive to drug treatment, and to test the feasibility of this intervention as complementary treatment for a psychiatric setting...
September 27, 2016: Behavioural and Cognitive Psychotherapy
Sara Razmjou, Darcy Litteljohn, Chris Rudyk, Shuaib Syed, Melanie Clarke, Rowan Pentz, Zach Dwyer, Shawn Hayley
Approximately one-third of patients with major depressive disorders (MDDs) are resistant to current treatment methods, and the majority of cases relapse at some point during therapy. This has resulted in novel treatments being adopted, including subanesthetic doses of ketamine, which affects aberrant neuroplastic circuits, glutamatergic signaling, and the production of brain-derived neurotrophic factor. Ketamine rapidly relieves depressive symptoms in treatment-resistant major depressive disorder patients with effects that last for up to 2 weeks even after a single administration...
2016: Neuropsychiatric Disease and Treatment
D M Rotroff, D G Corum, A Motsinger-Reif, O Fiehn, N Bottrel, W C Drevets, J Singh, G Salvadore, R Kaddurah-Daouk
Ketamine, at sub-anesthetic doses, is reported to rapidly decrease depression symptoms in patients with treatment-resistant major depressive disorder (MDD). Many patients do not respond to currently available antidepressants, (for example, serotonin reuptake inhibitors), making ketamine and its enantiomer, esketamine, potentially attractive options for treatment-resistant MDD. Although mechanisms by which ketamine/esketamine may produce antidepressant effects have been hypothesized on the basis of preclinical data, the neurobiological correlates of the rapid therapeutic response observed in patients receiving treatment have not been established...
2016: Translational Psychiatry
Kenji Hashimoto
The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is one of the most attractive antidepressants since this drug causes rapid-onset and sustained antidepressant effects in treatment resistant patients with depression. There are unanswered questions about how ketamine induces its rapid and sustained antidepressant actions. This key article suggests that (2R,6R)-HNK (hydroxynorketamine), a major metabolite of (R)-ketamine, shows antidepressant effects in rodent models of depression, indicating that the metabolism of (R)-ketamine to (2R,6R)-HNK is pivotal in its antidepressant action...
November 2016: Expert Opinion on Therapeutic Targets
Kohji Shirai
BACKGROUND: The cardio-ankle vascular index (CAVI) is a new arterial stiffness index of the arterial tree from the origin of the aorta to the ankle, and was essentially derived from the stiffness parameterβtheory proposed by Hayashi. The conspicuous feature of CAVI is independency from blood pressure at the time of measurement. AIM: The purpose is to clarify the meaning of CAVI as a surrogate marker of arteriosclerosis, and also the role of CAVI in the blood pressure control system...
September 2016: Journal of Hypertension
Q S Li, C Tian, G R Seabrook, W C Drevets, V A Narayan
Genetic predisposition may contribute to the differences in drug-specific, class-specific or antidepressant-wide treatment resistance. Clinical studies with the genetic data are often limited in sample sizes. Drug response obtained from self-reports may offer an alternative approach to conduct a study with much larger sample size. Using the phenotype data collected from 23andMe 'Antidepressant Efficacy and Side Effects' survey and genotype data from 23andMe's research participants, we conducted genome-wide association study (GWAS) on subjects of European ancestry using four groups of phenotypes (a) non-treatment-resistant depression (n=7795) vs treatment-resistant depression (TRD, n=1311), (b) selective serotonin reuptake inhibitors (SSRI) responders (n=6348) vs non-responders (n=3340), (c) citalopram/escitalopram responders (n=2963) vs non-responders (n=2005), and (d) norepinephrine-dopamine reuptake inhibitor (NDRI, bupropion) responders (n=2675) vs non-responders (n=1861)...
2016: Translational Psychiatry
Camilo Alfonso Espinosa Jovel, Sergio Ramírez Salazar, Carlos Rincón Rodríguez, Fidel Ernesto Sobrino Mejía
OBJECTIVE: Currently few studies describe the variables that impact quality of life (QoL) in patients with epilepsy in low-income populations. The study aimed to establish relationships between QoL scores obtained through the QOLIE-10 inventory and clinical variables in patients older than 18 years diagnosed with epilepsy. METHODS: We conducted an observational, descriptive, and cross-sectional study. We conducted consecutive recruitment of the data for all patients with an epilepsy diagnosis who were treated in the neurology department of Kennedy Western Hospital located in Bogota, Colombia...
September 1, 2016: Epilepsy Research
Patrick Micheels, Stéphanie Besse, Didier Sarrazin
BACKGROUND: Hyaluronic acid (HA) fillers are commonly used for enhancement of lips, and for softening fine lines and correcting skin depressions. OBJECTIVE: This study sought to investigate whether the Vycross<sup>™</sup> technology used for Volbella<sup>™</sup> gel resulted in a cohesive gel, as documented in our previous studies with three other HA fillers (Restylane<sup>®</sup> NASHA<sup>™</sup> [Q-MED, Uppsala, Sweden], Esthélis<sup>®</sup> Basic CPM™ [Anteis SA, Geneva, Switzerland], and Juvéderm<sup>®</sup> Ultra 3 using Hylacross technology [Allergan, Irvine, CA, USA])...
September 1, 2016: Journal of Drugs in Dermatology: JDD
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