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Drug resistant depression

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
Alexander V Kulikov, Raul R Gainetdinov, Evgeni Ponimaskin, Allan V Kalueff, Vladimir S Naumenko, Nina K Popova
Selective serotonin reuptake inhibitors (SSRIs) are the most effective and most used antidepressant drugs. Acting by inhibiting serotonin (5-HT) transporter, SSRIs display a typical 3-4-week delay in their therapeutic effects, with nearly 40% of depressed patients remaining treatment-resistant. Recent evidence suggests complex interplay between 5-HT receptors and key proteins of 5-HT metabolism in molecular mechanisms of such delay and resistance to SSRIs. Area covered: This paper concentrates on the interplay between 5-HT receptors in the delay of therapeutic effect of SSRIs, and the interaction between tryptophan hydroxylase 2 and 5-HT transporter in the SSRI resistance...
March 15, 2018: Expert Opinion on Therapeutic Targets
V Lew, E McKay, M Maze
Introduction: For a drug that has been omnipresent for nearly 200 years, nitrous oxide's (N2O) future seems less certain than its illustrious past. Environmental concerns are coming to the fore and may yet outweigh important clinical benefits. Sources of data: After determining the scope of the review, the authors used PubMed with select phrases encompassing the words in the scope. Both preclinical and clinical reports were considered. Areas of agreement: The analgesic and anaesthetic advantages of N2O remain despite a plethora of newer agents...
March 8, 2018: British Medical Bulletin
M Dold, L Bartova, J Mendlewicz, D Souery, A Serretti, S Porcelli, J Zohar, S Montgomery, S Kasper
OBJECTIVE: This multicenter, multinational, cross-sectional study aimed to investigate clinical characteristics and treatment outcomes associated with augmentation/combination treatment strategies in major depressive disorder (MDD). METHOD: Sociodemographic, clinical, and treatment features of 1410 adult MDD patients were compared between MDD patients treated with monotherapy and augmentation/combination medication using descriptive statistics, analyses of covariance (ancova), and Spearman's correlation analyses...
February 28, 2018: Acta Psychiatrica Scandinavica
Elizabeth Galik, Sarah Holmes, Barbara Resnick
INTRODUCTION: The purpose of this study was to test differences in psychotropic medication, function, physical activity, agitation, resistiveness to care, comorbidities, and depression among moderate to severely cognitively impaired nursing home residents who were fallers versus nonfallers. METHODS: This was a secondary data analysis using baseline data from a randomized controlled trial testing the Function and Behavior Focused Care intervention across 12 nursing homes...
January 1, 2018: American Journal of Alzheimer's Disease and Other Dementias
Rani A Sarkis, Scott McGinnis, Sara N Rushia, Suna Park, Emile E Ansari, Kim C Willment
We aimed to investigate the cognitive and psychosocial outcomes of patients older than 50 with drug-resistant temporal lobe epilepsy as compared to a younger cohort. One hundred and thirty-one patients with temporal lobe epilepsy (47% age ≥ 50) who underwent comprehensive neuropsychological testing were retrospectively identified. A comparison of percentage of Z scores < - 1.5 between the older and younger cohort on Trail Making Tests A and B, Boston Naming Test, Rey Auditory Verbal Learning Test (RAVLT) delayed recall, and Rey-Osterrieth complex figure test delayed recall was performed as well as the presence of disability due to epilepsy and depression scores...
February 24, 2018: Journal of Neurology
Andrea Cipriani, Toshi A Furukawa, Georgia Salanti, Anna Chaimani, Lauren Z Atkinson, Yusuke Ogawa, Stefan Leucht, Henricus G Ruhe, Erick H Turner, Julian P T Higgins, Matthias Egger, Nozomi Takeshima, Yu Hayasaka, Hissei Imai, Kiyomi Shinohara, Aran Tajika, John P A Ioannidis, John R Geddes
BACKGROUND: Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder...
February 20, 2018: Lancet
Sean J Belouin, Jack E Henningfield
The purpose of this commentary is to provide an introduction to this special issue of Neuropharmacology with a historical perspective of psychedelic drug research, their use in psychiatric disorders, research-restricting regulatory controls, and their recent emergence as potential breakthrough therapies for several brain-related disorders. It begins with the discovery of lysergic acid diethylamide (LSD) and its promising development as a treatment for several types of mental illnesses during the 1940s. This was followed by its abuse and stigmatization in the 1960s that ultimately led to the placement of LSD and other psychedelic drugs into the most restrictively regulated drug schedule of the United States Controlled Substances Act (Schedule I) in 1970 and its international counterparts...
February 21, 2018: Neuropharmacology
Konstantinos V Floros, Timothy L Lochmann, Bin Hu, Carles Monterrubio, Mark T Hughes, Jason D Wells, Cristina Bernadó Morales, Maninderjit S Ghotra, Carlotta Costa, Andrew J Souers, Sosipatros A Boikos, Joel D Leverson, Ming Tan, Violeta Serra, Jennifer E Koblinski, Joaquin Arribas, Aleix Prat, Laia Paré, Todd W Miller, Mikhail G Dozmorov, Hisashi Harada, Brad E Windle, Maurizio Scaltriti, Anthony C Faber
HER2 ( ERBB2 ) amplification is a driving oncogenic event in breast cancer. Clinical trials have consistently shown the benefit of HER2 inhibitors (HER2i) in treating patients with both local and advanced HER2+ breast cancer. Despite this benefit, their efficacy as single agents is limited, unlike the robust responses to other receptor tyrosine kinase inhibitors like EGFR inhibitors in EGFR -mutant lung cancer. Interestingly, the lack of HER2i efficacy occurs despite sufficient intracellular signaling shutdown following HER2i treatment...
February 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
Takuma Uo, Stephen R Plymate, Cynthia C Sprenger
The androgen receptor variant AR-V7 is gaining attention as a potential predictive marker for as well as one of the resistance mechanisms to the most current anti-androgen receptor (AR) therapies in castration-resistant prostate cancer (CRPC). Accordingly, development of next-generation drugs that directly or indirectly target AR-V7 signaling is urgently needed. Areas covered: We review proposed mechanisms of drug resistance in relation to AR-V7 status, the mechanisms of generation of AR-V7, and its transcriptome, cistrome, and interactome...
February 8, 2018: Expert Opinion on Therapeutic Targets
Virupakshi Jalihal, Rohit Shankar, William Henley, Mary Parrett, Phil Tittensor, Brendan N McLean, Ammad Ahmed, Josemir W Sander
BACKGROUND: Psychiatric and behavioral side effects (PBSEs) are a major cause of antiepileptic drug (AED) withdrawal. Levetiracetam (LEV) is a recognized first-line AED with good seizure outcomes but recognized with PBSEs. Eslicarbazepine (ESL) is considered to function similarly to an active metabolite of the commonly used carbamazepine (CBZ). Carbamazepine is used as psychotropic medication to assist in various psychiatric illnesses such as mood disorders, aggression, and anxiety. AIM: The aim was to evaluate the psychiatric profile of ESL in people who had LEV withdrawn due to PBSEs in routine clinical practice to see if ESL can be used as a possible alternative to LEV...
February 4, 2018: Epilepsy & Behavior: E&B
Siew-Tim Lai, Kheng-Seang Lim, Venus Tang, Wah-Yun Low
BACKGROUND: Positive psychological interventions (PPI) are increasingly employed as a coping strategy with physical and mental conditions, including neurological diseases. Its effectiveness on improving wellbeing in people with epilepsy (PWE) has been shown in a few studies. This study aimed to explore factors related to participants' willingness to engage in psychological interventions from the perspective of patients with epilepsy. METHODS: Participants answered a needs assessment questionnaire eliciting information about their illness perception (Brief Illness Perception Questionnaire (Brief-IPQ)), emotions (Hospital Anxiety and Depression Scale (HADS)), willingness to participate in psychological interventions, preferences in types of PPI and intervention designs, as well as barriers in seeking mental health services...
January 23, 2018: Epilepsy & Behavior: E&B
Mendel Kaelen, Bruna Giribaldi, Jordan Raine, Lisa Evans, Christopher Timmerman, Natalie Rodriguez, Leor Roseman, Amanda Feilding, David Nutt, Robin Carhart-Harris
RATIONALE: Recent studies have supported the safety and efficacy of psychedelic therapy for mood disorders and addiction. Music is considered an important component in the treatment model, but little empirical research has been done to examine the magnitude and nature of its therapeutic role. OBJECTIVES: The present study assessed the influence of music on the acute experience and clinical outcomes of psychedelic therapy. METHODS: Semi-structured interviews inquired about the different ways in which music influenced the experience of 19 patients undergoing psychedelic therapy with psilocybin for treatment-resistant depression...
February 2018: Psychopharmacology
Chinnakkaruppan Adaikkan, Elham Taha, Iliana Barrera, Orit David, Kobi Rosenblum
BACKGROUND: Ketamine is an N-methyl-D-aspartate receptor antagonist, which on administration produces fast-acting antidepressant responses in patients with major depressive disorder. Yet, the mechanism underlying the antidepressant action of ketamine remains unclear. METHODS: To unravel the mechanism of action of ketamine, we treated wild-type C57BL/6 mice with calcium/calmodulin-dependent protein kinase II (CaMKII) specific inhibitor tatCN21 peptide. We also used eukaryotic elongation factor 2 kinase (eEF2K) (also known as CaMKIII) knockout mice...
December 5, 2017: Biological Psychiatry
Volker M Tronnier, Dirk Rasche, Veronika Thorns, Daniel Alvarez-Fischer, Thomas F Münte, Bartosz Zurowski
Obese individuals share behavioral characteristics with drug/alcohol addicts as well as obsessive compulsive disease. Deep brain stimulation (DBS) has been used successfully in these disorders, thus warranting an evaluation in obesity. A woman with treatment-resistant depression as well as severe obesity was selected for DBS of the nucleus accumbens (NAcc) bilaterally with depression being the primary and obesity being the secondary target of treatment. Compared to earlier bariatric surgery, the patient showed accelerated weight loss after DBS...
February 1, 2018: Neurocase
Ahmed T Ahmed, Richard Weinshilboum, Mark A Frye
Antidepressants have reduced the symptom burden for many Major Depressive Disorder (MDD) patients, but drug-related side effects and treatment resistance continue to present major challenges. Pharmacogenomics represents one approach to enhance antidepressant efficacy and avoid adverse reactions, but concerns remain with regard to the overall "value equation," and several barriers must be overcome to achieve the full potential of MDD pharmacogenomics.
February 1, 2018: Clinical Pharmacology and Therapeutics
Ira Byock
BACKGROUND: Psychiatric research in the 1950s and 1960s showed potential for psychedelic medications to markedly alleviate depression and suffering associated with terminal illness. More recent published studies have demonstrated the safety and efficacy of psilocybin, MDMA, and ketamine when administered in a medically supervised and monitored approach. A single or brief series of sessions often results in substantial and sustained improvement among people with treatment-resistant depression and anxiety, including those with serious medical conditions...
January 22, 2018: Journal of Palliative Medicine
Alexandra Neyazi, Wiebke Theilmann, Claudia Brandt, Tomi Rantamäki, Nobuaki Matsui, Mathias Rhein, Johannes Kornhuber, Malek Bajbouj, Wolfgang Sperling, Stefan Bleich, Helge Frieling, Wolfgang Löscher
Although electroconvulsive therapy (ECT) is among the most effective treatment options for pharmacoresistant major depressive disorder (MDD), some patients still remain refractory to standard ECT practise. Thus, there is a need for markers reliably predicting ECT non/response. In our study, we have taken a novel translational approach for discovering potential biomarkers for the prediction of ECT response. Our hypothesis was that the promoter methylation of p11, a multifunctional protein involved in both depressive-like states and antidepressant treatment responses, is differently regulated in ECT responders vs...
January 22, 2018: Translational Psychiatry
Johann Steiner, Brisa S Fernandes, Paul C Guest, Henrik Dobrowolny, Gabriela Meyer-Lotz, Sabine Westphal, Katrin Borucki, Kolja Schiltz, Zoltán Sarnyai, Hans-Gert Bernstein
There is evidence for insulin resistance in drug-naïve first-episode schizophrenia (Sz) patients. We have tested whether impaired insulin homeostasis is also present in first-episode patients with major depression (MD) and if this can be discerned from stress-related and medication effects. Homeostatic model assessment of insulin resistance (HOMA-IR) was determined in a cross-sectional cohort study of acute first-episode drug-naïve patients with MD (n = 18) or Sz (n = 24), and healthy controls (C, n = 43)...
January 19, 2018: European Archives of Psychiatry and Clinical Neuroscience
Tyler J Wilson, Meghan S Blackledge, Patrick A Vigueira
The rapid increase in bacterial resistance to antibiotics is a global healthcare crisis. Non-antibiotic pharmaceuticals that have attained approval by the United States Food and Drug Administration have the potential to be repurposed as bacterial resistance-modifying agents and therefore could become valuable resources in our battle against antibiotic-resistant microbes. Amoxapine is a tetracyclic antidepressant used in the treatment of major depressive disorder. Here we demonstrate the ability of amoxapine to resensitize methicillin-resistant Staphylococcus aureus strain ATCC 43300 to oxacillin in both agar diffusion and broth microdilution assays...
January 2018: Heliyon
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