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Verònica Gálvez, Adrienne Li, Christina Huggins, Paul Glue, Donel Martin, Andrew A Somogyi, Angelo Alonzo, Anthony Rodgers, Philip B Mitchell, Colleen K Loo
BACKGROUND: Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments. METHODS: This randomised, double-blind, placebo-controlled pilot study compared a 4-week course of eight treatments of 100 mg ketamine or 4.5 mg midazolam...
March 1, 2018: Journal of Psychopharmacology
Ginetta Collo, Laura Cavalleri, Federica Bono, Cristina Mora, Stefania Fedele, Roberto William Invernizzi, Massimo Gennarelli, Giovanna Piovani, Tilo Kunath, Mark J Millan, Emilio Merlo Pich, PierFranco Spano
The antiparkinsonian ropinirole and pramipexole are D3 receptor- (D3R-) preferring dopaminergic (DA) agonists used as adjunctive therapeutics for the treatment resistant depression (TRD). While the exact antidepressant mechanism of action remains uncertain, a role for D3R in the restoration of impaired neuroplasticity occurring in TRD has been proposed. Since D3R agonists are highly expressed on DA neurons in humans, we studied the effect of ropinirole and pramipexole on structural plasticity using a translational model of human-inducible pluripotent stem cells (hiPSCs)...
2018: Neural Plasticity
Bettina H Bewernick, Hannah M Kilian, Klaudius Schmidt, Ruth E Reinfeldt, Sarah Kayser, Volker A Coenen, Sebastian Markett, Thomas E Schlaepfer
BACKGROUND: Reports of changes in patients' social behavior during deep brain stimulation (DBS) raised the question whether DBS induces changes in personality. This study explored if (1) DBS is associated with changes in personality in patients suffering from treatment-resistant depression (TRD), (2) how personality dimensions and depression are associated, and (3) if TRD patients' self-ratings of personality are valid. METHODS: TRD patients were assessed before DBS (n = 30), 6 months (t2, n = 21), 2 (t3, n = 17) and 5 years (t4, n = 11) after the initiation of DBS of the supero-lateral branch of the medial forebrain bundle (slMFB-DBS)...
March 1, 2018: Psychological Medicine
Nathalie Alvarez-Ricartes, Patricia Oliveros-Matus, Cristhian Mendoza, Nelson Perez-Urrutia, Florencia Echeverria, Alexandre Iarkov, George E Barreto, Valentina Echeverria
Failure in fear extinction is one of the more troublesome characteristics of posttraumatic stress disorder (PTSD). Cotinine facilitates fear memory extinction and reduces depressive-like behavior when administered 24 h after fear conditioning in mice. In this study, it was investigated the behavioral and molecular effects of cotinine, and other antidepressant preparations infused intranasally. Intranasal (IN) cotinine, IN krill oil, IN cotinine plus krill oil, and oral sertraline were evaluated on depressive-like behavior and fear retention and extinction after fear conditioning in C57BL/6 mice...
February 27, 2018: Molecular Neurobiology
Mark Olfson, Tony B Amos, Carmela Benson, Jacquelyn McRae, Steven C Marcus
BACKGROUND: Although the clinical and health economic characteristics of commercially insured adults with treatment-resistant depression (TRD) have been well characterized, little is known about TRD in the Medicaid population. OBJECTIVE: To describe clinical and health economic characteristics of adult Medicaid beneficiaries with TRD. METHODS: Retrospective longitudinal cohort analyses were performed with Truven Health MarketScan Medicaid Database (2008-2014), focusing on adults with major depressive disorder (MDD) following an index antidepressant prescription...
March 2018: Journal of Managed Care & Specialty Pharmacy
M P Dandekar, A J Fenoy, A F Carvalho, J C Soares, J Quevedo
Although deep brain stimulation (DBS) is an established treatment choice for Parkinson's disease (PD), essential tremor and movement disorders, its effectiveness for the management of treatment-resistant depression (TRD) remains unclear. Herein, we conducted an integrative review on major neuroanatomical targets of DBS pursued for the treatment of intractable TRD. The aim of this review article is to provide a critical discussion of possible underlying mechanisms for DBS-generated antidepressant effects identified in preclinical studies and clinical trials, and to determine which brain target(s) elicited the most promising outcomes considering acute and maintenance treatment of TRD...
February 27, 2018: Molecular Psychiatry
Tony B Amos, Neeta Tandon, Patrick Lefebvre, Dominic Pilon, Rhiannon L Kamstra, Irina Pivneva, Paul E Greenberg
BACKGROUND: Treatment-resistant depression (TRD) poses a substantial burden to health care payers including employers, costing an estimated $29 billion-$48 billion yearly in the United States. Furthermore, variation of burden across increasing levels of resistance and the potential impact of TRD on employment status remain largely unexplored. OBJECTIVE: To evaluate health care resource utilization (HRU) and costs, work loss, indirect costs, and employment status change in TRD...
February 20, 2018: Journal of Clinical Psychiatry
Jiajia Zhu, Huanhuan Cai, Yonggui Yuan, Yingying Yue, Deguo Jiang, Ce Chen, Wei Zhang, Chuanjun Zhuo, Yongqiang Yu
Several behavioral and neuroimaging markers could be used to predict eventual antidepressant medication (ADM) outcomes in patients with major depressive disorder (MDD). However, these predictors are either subjective or complex, which has limited their clinical use. Thus, we aimed to identify an objective and easy-to-get marker to predict early therapeutic efficacy. Forty-seven drug-naïve patients with MDD and 47 age-, gender- and education-matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) scans...
February 23, 2018: Brain Imaging and Behavior
Shuxin Luan, Hongquan Wan, Lei Zhang, Hua Zhao
Background: Treatment-resistant depression (TRD) is common and potentially life-threatening in adults, and the benefits and risks of adjunctive aripiprazole in these patients remain controversial. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy, acceptability, safety, and quality of life of adjunctive aripiprazole in patients with TRD. Methods: RCTs published in PubMed, Web of Science, and Embase were systematically reviewed to evaluate the efficacy and safety profiles of TRD patients who were treated with adjunctive aripiprazole...
2018: Neuropsychiatric Disease and Treatment
Taimoor I Sheikh, Ricardo Harripaul, Muhammad Ayub, John B Vincent
Mutations in the Methyl-CpG-binding protein-2 gene (MECP2) are commonly associated with Rett syndrome. However, it has long been appreciated that there exists a spectrum of neuropsychiatric phenotypes associated with MECP2 variants. The most frequent Rett missense mutations are located in either the methyl-CpG-binding domain (MBD) or transcription repression domain (TRD). Clinical roles for mutations in other domains such as the intervening domain (ID) or AT-Hook domains have yet to be determined. Here, we report functional analysis of MECP2 missense mutations, located in AT-Hook1 within the ID, in a large Pakistani family with childhood onset cognitive decline and schizophrenia, de novo in a girl with atypical Rett syndrome, and de novo in a woman with schizophrenia...
February 12, 2018: Human Mutation
Ilda D'Annessa, Anna Gandaglia, Elena Brivio, Gilda Stefanelli, Angelisa Frasca, Nicoletta Landsberger, Daniele Di Marino
Mutations in the X-linked MECP2 gene represent the main origin of Rett syndrome, causing a profound intellectual disability in females. MeCP2 is an epigenetic transcriptional regulator containing two main functional domains: a methyl-CpG binding domain (MBD) and a transcription repression domain (TRD). Over 600 pathogenic mutations were reported to affect the whole protein; almost half of missense mutations affect the MBD. Understanding the impact of these mutations on the MBD structure and interaction with DNA will foster the comprehension of their pathogenicity and possibly genotype/phenotype correlation studies...
February 8, 2018: Biochimica et Biophysica Acta
François Trottier-Duclos, Véronique Desbeaumes Jodoin, Marie-Pierre Fournier-Gosselin, François Richer, Nathalie Desjardins, Sylvie Tieu, Paul Lespérance
OBJECTIVES: Treatment-resistant depression (TRD) carries a major burden on those affected by this disease and significantly impacts their quality of life (QOL). Vagus nerve stimulation (VNS) has showed promising results on symptoms, but its impact on QOL remains underresearched. This study aims to evaluate the long-term effects of VNS on both QOL and clinical symptoms for TRD patients, through a naturalistic 6-year follow-up. METHOD: Outpatients with confirmed TRD were enrolled to receive VNS...
February 7, 2018: Journal of ECT
Rania Ghorbel, Raouia Ghorbel, Aida Rouissi, Nourhene Fendri-Kriaa, Ghada Ben Saleh, Neila Belguith, Leila Ammar-Keskes, Neziha Gouider-Khouja, Faiza Fakhfakh
Rett syndrome is an X-linked neurodevelopmental disorder that develops a profound intellectual and motor disability and affects 1 from 10 000 to 15 000 live female births. This disease is characterized by a period of apparently normal development until 6-18 months of age when motor and communication abilities regress which is caused by mutations occurred in the X-linked MECP2 gene, encoding the methyl-CpG binding protein 2. This research study reports a molecular analysis via an exhaustive gene sequencing which reveals an unusual novel double mutation (c...
February 5, 2018: Biochemical and Biophysical Research Communications
Albert S Li, Antonio Capone, Michael T Trese, Jonathan E Sears, Andres Kychenthal, Irina De la Huerta, Philip J Ferrone
PURPOSE: To evaluate the long-term outcomes of treatment of total exudative retinal detachments (ERDs) secondary to Coats disease (stage 3B) and the role of vitrectomy. DESIGN: Retrospective, observational case series. PARTICIPANTS: A total of 16 eyes in 16 patients undergoing treatment for total ERDs secondary to Coats disease with at least 5 years of follow-up. METHODS: We reviewed the records of patients with stage 3B Coats disease...
January 17, 2018: Ophthalmology
Taylor Lyons, Robin L Carhart-Harris
RATIONALE: Previous research suggests that classical psychedelic compounds can induce lasting changes in personality traits, attitudes and beliefs in both healthy subjects and patient populations. AIM: Here we sought to investigate the effects of psilocybin on nature relatedness and libertarian-authoritarian political perspective in patients with treatment-resistant depression (TRD). METHODS: This open-label pilot study with a mixed-model design studied the effects of psilocybin on measures of nature relatedness and libertarian-authoritarian political perspective in patients with moderate to severe TRD ( n=7) versus age-matched non-treated healthy control subjects ( n=7)...
January 1, 2018: Journal of Psychopharmacology
An Qin, Jian Liang, Xiao Han, Nicolette O'Connell, Di Yan
PURPOSE: To investigate the clinical-relevant discrepancy between doses warped by pure-image based deformable image registration (IM-DIR) and by biomechanical-model based DIR (BM-DIR) on intensity homogeneous organs. METHODS AND MATERIALS: Ten patients (5Head&Neck, 5Prostate) were included. A research DIR tool (ADMRIE_v1.12) was utilized for IM-DIR. After IM-DIR, BM-DIR was carried out for organs (parotids, bladder, and rectum) which often encompass sharp dose gradient...
January 3, 2018: Medical Physics
R Court, L Wiesner, A Stewart, N de Vries, J Harding, G Maartens, T Gumbo, H McIlleron
SETTING: Terizidone/cycloserine (TRD/CS) is included in standard treatment regimens for multidrug-resistant tuberculosis (MDR-TB) in many countries. The steady state pharmacokinetics (PKs) of CS after TRD administration are not known. OBJECTIVES AND DESIGN: We recruited in-patients treated with 250-750 mg oral TRD daily as part of standard treatment regimens for pulmonary MDR-TB in Cape Town, South Africa. Plasma CS assays were performed in samples taken pre-dose and at 2, 4, 6, 8 and 10 h post-dose...
January 1, 2018: International Journal of Tuberculosis and Lung Disease
Ella J Daly, Jaskaran B Singh, Maggie Fedgchin, Kimberly Cooper, Pilar Lim, Richard C Shelton, Michael E Thase, Andrew Winokur, Luc Van Nueten, Husseini Manji, Wayne C Drevets
Importance: Approximately one-third of patients with major depressive disorder (MDD) do not respond to available antidepressants. Objective: To assess the efficacy, safety, and dose-response of intranasal esketamine hydrochloride in patients with treatment-resistant depression (TRD). Design, Setting, and Participants: This phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study was conducted in multiple outpatient referral centers from January 28, 2014, to September 25, 2015...
February 1, 2018: JAMA Psychiatry
Paul McCrone, Felicitas Rost, Leonardo Koeser, Iakovina Koutoufa, Stephanie Stephanou, Martin Knapp, David Goldberg, David Taylor, Peter Fonagy
BACKGROUND: Patients with treatment-resistant depression (TRD) suffer very significant morbidity and are at a disadvantage concerning optimal clinical management. There are high associated societal costs. AIMS: A detailed analysis of health economic costs in the United Kingdom in a group manifesting a severe form of TRD in the 12 months before their participation in a major randomized controlled treatment trial. METHODS: The sample consisted of 118 participants from the Tavistock Adult Depression Study...
December 23, 2017: Journal of Mental Health
M Soledad Cepeda, Jenna Reps, Daniel Fife, Clair Blacketer, Paul Stang, Patrick Ryan
BACKGROUND: Depression that does not respond to antidepressants is treatment-resistant depression (TRD). TRD definitions include assessments of treatment response, dose and duration, and implementing these definitions in claims databases can be challenging. We built a data-driven TRD definition and evaluated its performance. METHODS: We included adults with depression, ≥1 antidepressant, and no diagnosis of mania, dementia, or psychosis. Subjects were stratified into those with and without proxy for TRD...
December 15, 2017: Depression and Anxiety
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