This unique book presents the treatment "roadmap" implemented by the University of Michigan Comprehensive Depression Center's Treatment Resistant Depression Program, step-by-step guidance that has long eluded clinicians, patients, and their ...
Author: John F. Greden
Publisher: American Psychiatric Pub
This unique book presents the treatment "roadmap" implemented by the University of Michigan Comprehensive Depression Center's Treatment Resistant Depression Program, step-by-step guidance that has long eluded clinicians, patients, and their families. Writing across discipline, modality, lifespan, and patient demographics, the authors have compiled the most current thinking on TRD and distilled it into a highly readable, imminently practical, and brilliantly organized source of hope. The authors believe that early intervention is critical, and they advocate strategies for renewed focus on identifying youths who are at risk or already symptomatic. Similarly, they devote chapters to special populations such as pregnant women, older people, and those with comorbidities. Perhaps most useful to patients and their families, the book has a strong self-care orientation, emphasizing the importance of exercise, nutrition, and healthy sleep guidelines. Patients who are actively engaged in managing their disease often have better outcomes. Treatment Resistant Depression is frequently a lifetime diagnosis. The book acknowledges that fact and offers a systematic course of treatment grounded in evidence-based research that is current and comprehensive. Treatment Resistant Depression: A Roadmap for Effective Care offers a new way of conceptualizing an old enemy, and should prove to be an indispensable weapon in the battle.
This book brings together an international group of clinicians and researchers from a broad swath of inter-related disciplines to offer the most up-to-date information about clinical and preclinical research into ketamine and second ...
Author: Sanjay J. Mathew
This book brings together an international group of clinicians and researchers from a broad swath of inter-related disciplines to offer the most up-to-date information about clinical and preclinical research into ketamine and second-generation “ketamine-like” fast-acting antidepressants. Currently available antidepressant medications act through monoaminergic systems, are ineffective for many individuals suffering from depression, and are associated with a delayed onset of peak efficacy of several months. The unexpected emergence of ketamine, an anesthetic N-methyl-D-aspartate (NMDA) receptor antagonist, as a rapid-acting antidepressant has reinvigorated CNS drug discovery research and catalyzed investigation in patient populations historically ignored in antidepressant drug development programs, particularly treatment-resistant patients and those with suicidality. Recent industry and academic research efforts have coalesced to explore NMDA receptor and glutamatergic molecular targets that lack ketamine’s psychotomimetic side effects and abuse liability but retain its rapid onset of efficacy. However, many fundamental questions remain regarding the neurobiological mechanisms underlying ketamine’s rapid antidepressant effects and the puzzling persistence of benefits observed in some patients following a single dose. This book examines how insights from these studies are forging new conceptual models of the neurobiology of stress-related affective, anxiety, and addictive disorders and the nature of treatment resistance. It also discusses how ketamine’s rapid antidepressant effects provide a scientific platform to facilitate innovation in clinical trial designs pertaining to patient selection, choice of control group, outcome measures, and dose-optimization. This book brings together data and insights from this rapidly expanding and extraordinarily promising field of study. Readers will be able to extract integrated themes and useful insights from the material contained in these diverse chapters and appreciate the paradigm-shifting contributions of ketamine to modern psychiatry and clinical neuroscience research.
1. Major depressive disorder and treatment-resistant depression. 1.1.
Author: George I. Papakostas
Publisher: World Scientific
This unique ground-breaking work, authored by renowned Harvard-based researchers G I Papakostas and M Fava, represents, by far, the most comprehensive compilation to date of medical studies and reports involving the use of anti-depressants for the treatment of major depressive disorder, one of the most prevalent and devastating medical illnesses afflicting mankind today. Given the breadth of the scientific literature focusing on the use of anti-depressants for major depressive disorder, this work represents an invaluable tool for clinicians as well as scientists in search of a reference manual to help guide them through the field. The book is organized into four parts; each part focusing on a separate theme that will facilitate the reader to precisely access particular information of interest, whether be it clinical or scientific in nature. Each part is then sub-divided into several thematic chapters, which are enriched with tables and figures citing results from the most influential studies in the field. Finally, clinical and research pearls are listed throughout the book in bullet-point fashion to help summarize the available knowledge-base in a user-friendly format.
Long-term effects of nucleus accumbens deep brain stimulation in treatment- resistant depression: evidence for sustained efficacy. Neuropsychopharmacology
. 2012;37(9):1975e1985. https://doi.org/ 10.1038/npp.2012.44. 268. Jime ́nez F ...
Author: Gustavo H. Vazquez
Publisher: Academic Press
Ketamine for Treatment-Resistant Depression: Neurobiology and Applications provides a simple, evidence-based overview for neuropsychiatrists and translational researchers on this medication, its mechanisms of actions, eligibility of patients for treatment, and the preparation and implementation of ketamine clinics. Provides efficacy research on ketamine as a treatment for depression Identifies best practices for clinical use, both long-term and acute Discusses the molecular mechanisms and neurobiology of action
Conclusions: This is the first study to investigate excess mortality in individuals with TRD first identified in primary care and our findings emphasize the need for prevention of suicide in individuals with depression when they do not ...
Author: Trine Munk-Olsen
Objective: Depression is associated with excess mortality, but it is not yet known how treatment-resistance influences life expectancy. This study estimates all-cause and cause-specific mortality rate ratios (MRR) and excess Life Years Lost (LYL) in individuals with treatment-resistant depression (TRD) first identified in primary care. Methods: All individuals born and living in Denmark who filled their first prescription for an antidepressant drug at age 18-69 years between 1996 and 2012 were identified in the Danish National Prescription Registry (N=562,648). Individuals with at least two additional different treatment trials within three years were classified as TRD. MRRs were estimated with Cox Proportional Hazards regression adjusted for age at first prescription, calendar year and comorbidity, and LYL by the Life Years Lost method. Results: Of the population, 27,920 (5%) individuals were identified with TRD. The study cohort was observed over 5,863,165 person-years (TRD: 278,002), in which there were 71,374 deaths (TRD: 2,901). Individuals with TRD had a significant excess mortality compared to individuals who respond to treatment. Adjusted MRRs between individuals with and without TRD was highest for suicide and accidents in both men (aMRR: 3.13, 95% CI 2.67; 3.66 and aMRR: 1.30, 95% CI 1.03; 1.65) and women (aMRR: 6.06, 95% CI 5.08; 7.23 and aMRR: 1.67, 95% CI 1.26; 1.65). Correspondingly, for men, diseases of the circulatory system, suicide, alcohol misuse and accidents accounted for the major shares of life-years lost in individuals with TRD, while for women, it was suicide, respiratory diseases and accidents. Conclusions: This is the first study to investigate excess mortality in individuals with TRD first identified in primary care and our findings emphasize the need for prevention of suicide in individuals with depression when they do not respond adequately to treatment.
Objectives: To forecast the burden of treatment-resistant depression (TRD) in the mature markets over the next ten years.Background and aims: TRD is a major public health problem.
Author: Mudasir Khan
Objectives: To forecast the burden of treatment-resistant depression (TRD) in the mature markets over the next ten years.Background and aims: TRD is a major public health problem. It results in the deterioration of the quality of life, increased healthcare costs, and in severe scenarios, suicides. This study aims to estimate the prevalence of TRD in the seven mature market countries over the next ten years.Materials and methods: Our analysis is based on a systematic review of the literature. We define TRD as a failure to respond after two or more antidepressant treatment trials of adequate dose and duration. These estimates and the prevalence of major depression was used to derive the prevalent cases of TRD across the seven mature market countries (France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States).To calculate the number of prevalent cases of TRD in each country, we multiplied the age-and gender-specific prevalence estimated from these studies by the United Nationsu2019 age-and gender-specific population estimates for each forecast year.Results: In 2019, the prevalence of TRD ranged from 0.3% in Japan to 1.8% in France. The prevalent cases of TRD will increase from 7.5 million in 2019 to 7.8 million in 2029.Conclusions: The increase in the number of prevalent TRD cases is driven by the increase in the prevalence of depression in addition to the demographic effects such as changes in the absolute size of the population at risk.
The patients received open-label treatment with L-Methylfolate (initial dose 400-800 mg/day, according to clinical response and tolerability). The primary outcome measured with the Montgomeryu2013Asberg Depression Rating Scale (MADRS).
Objectives:Depression is often associated with folate metabolism dysfunction and subsequent hyperhomocysteinemia. On the other hand, hyperhomocysteinemia can lead to depressive-like symptoms.Background:The aim of the study was to assess the effectiveness, tolerability, and safety of L-Methylfolate as an adjuvant treatment in adults with treatment-resistant depression and homocysteinemia associated with the MTHFR C667T/u04101298u0421 or MTRR A66G genotypes.Materials and Methods:We analyzed the data of 7 patients with treatment-resistant depression (2 family cases), who failed at least 2 adequate course of antidepressant treatment and had concurrent hyperhomocysteinemia. The patients received open-label treatment with L-Methylfolate (initial dose 400-800 mg/day, according to clinical response and tolerability). The primary outcome measured with the Montgomeryu2013Asberg Depression Rating Scale (MADRS). Subjective mood evaluated with the scale at baseline and after four weeks of treatment. Data about adverse effects related to L-Methylfolate and a self-harm risk assessment were also obtained.Results and Conclusions:Over the course of treatment, all patients showed more than 50% reduction of MADRS scores. The most frequently reported adverse effects were dizziness and nausea. No serious adverse effects were observed.In the case of homocysteinemia associated with the MTHFR C667T/u04101298u0421 and MTRR A66G genotypes and treatment-resistant depression, the precursor of vitamin B9, L-Methylfolate, should be used to improve treatment outcome. Further double-blind controlled trials of L-Methylfolate treatment are needed.
This book summarizes the latest evidence from clinical studies concerning the treatment of patients with treatment-resistant psychiatric disorders.
Author: Charles B. Nemeroff
Publisher: OUP USA
A sizable percentage of patients with major psychiatric disorders do not respond to the first or second treatments they receive. This book summarizes the latest evidence from clinical studies concerning the treatment of patients with treatment-resistant psychiatric disorders. Both pharmacological and psychotherapeutic interventions are included, as well as somatic non-pharmacological treatments. The chapter authors represent the leaders in their respective fields.
Introduction. Repetitive transcranial magnetic stimulation (rTMS) is a promising option for patients with treatment-resistant depression (TRD).
Author: Pavel Alfimov
Introduction. Repetitive transcranial magnetic stimulation (rTMS) is a promising option for patients with treatment-resistant depression (TRD). Reported response rates for rTMS in TRD are 45u201460%. A high rate of non-responders implicates a need for new treatment strategies. Those may include alternative rTMS protocols, e.g. theta-burst stimulation (TBS), use of different coils, etc.Purpose. We are reporting a case of a highly-resistant patient with recurrent depression, a 40-year-old male. Previously, he received adequate pharmacological treatment, and bilateral ECT. The treatment had minor-to-moderate and unsustainable effect. Cognitive disfunction was the most subjectively impairing symptom. The patient responded well to TBS.Methods. TBS parameters: 5Hz, 10 pulses/train, 30 trains, pause 8s, 15 sessions. During stimulation, the patient induced a u201cpositive emotional memory laneu201d. 5 additional u201cpro-cognitiveu201d rTMS sessions were performed (77Hz, 20 pulses, 5 trains, pause 8s, areas F3, Fz, F4, C3, Cz, C4, P3, Pz, P4). BDI and BAI scales were used for assessment. The pre-existing pharmacological regime was continued (olanzapine 15mg, clomipramine 300mg, lithium 600mg).Results. Initial assessment: BDI u2013 49, BAI u2013 26. After 4 TBS: BDI u2013 34, BAI u2013 13, subjective self-report u2013 a 50% improvement. After 15 TBS: BDI u2013 25, BAI u2013 6, persistent residual symptoms (anxiety, cognitive disfunction). After additional 5 sessions, a remission was achieved with good functioning and quality of life.Conclusion. An intensive and varying brain-stimulation approach may be successful in super-refractory depressed patients with u201cexhaustedu201d pharmacological options.
The index date for subjects with proxy for TRD was the procedure date, and for subjects without, the date of a randomly selected visit. We used three databases. We fit decision tree predictive models.
Abstract : 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. Proxies for TRD were electroconvulsive therapy, deep brain, or vagus nerve stimulation. The index date for subjects with proxy for TRD was the procedure date, and for subjects without, the date of a randomly selected visit. We used three databases. We fit decision tree predictive models. We included number of distinct antidepressants, with and without adequate doses and duration, number of antipsychotics and psychotherapies, and expert‐based definitions, 3, 6, and 12 months before index date. To assess performance, we calculated area under the curve (AUC) and transportability. Results: We analyzed 33, 336 subjects with no proxy for TRD, and 3, 566 with the proxy. Number of antidepressants and antipsychotics were selected in all periods. The best model was at 12 months with an AUC=0.81. The rule transported well and states that a subject with ≥1 antipsychotic or ≥3 antidepressants in the last year has TRD. Applying this rule, 15.8% of subjects treated for depression had TRD. Conclusion: The definition that best discriminates between subjects with and without TRD considers number of distinct antidepressants (≥3) or antipsychotics (≥1) in the last year.
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. Each treatment was given as 10 separate IN sprays, self-administered 5 min apart.
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. Each treatment was given as 10 separate IN sprays, self-administered 5 min apart. The study was stopped early due to poor tolerability after five treatment-resistant depressed participants were included. Feasibility, safety (acute and cumulative), cognitive and efficacy outcomes were assessed. Plasma ketamine and norketamine concentrations were assayed after the first treatment. Results: Significant acute cardiovascular, psychotomimetic and neurological side effects occurred at doses 100 mg ketamine. No participants were able to self-administer all 10 ketamine sprays due to incoordination; treatment time occasionally had to be extended (45 min) due to acute side effects. No hepatic, cognitive or urinary changes were observed after the treatment course in either group. There was an approximately two-fold variation in ketamine and norketamine plasma concentrations between ketamine participants. At course end, one participant had remitted in each of the ketamine and midazolam groups. Conclusions: IN ketamine, with the drug formulation and delivery device used, was not a useful treatment approach in this study. Absorption was variable between individuals and acute tolerability was poor, requiring prolonged treatment administration time in some individuals. The drug formulation, the delivery device, the insufflation technique and individual patient factors play an important role in tolerability and efficacy when using IN ketamine for TRD.
Given the unacceptably high rates of suffering, disability and premature death experienced by people with treatment-resistant depression and the surprisingly low rates of problems arising from the use of ketamine to treat the disorder, this ...
Author: Dr. Stephen J. Hyde
Publisher: Xlibris Corporation
Category: Health & Fitness
Given the unacceptably high rates of suffering, disability and premature death experienced by people with treatment-resistant depression and the surprisingly low rates of problems arising from the use of ketamine to treat the disorder, this is a therapy that all patients and their doctors should be discussing. This book summarises the research that has been carried out into ketamine for the treatment of depression over the past 15 years and, most importantly, describes different ways of using ketamine that are both practical and cost–effective. Currently most ketamine therapy is given intravenously in specialised clinics at considerable expense, but the author has successfully treated patients with low-dose sublingual ketamine and his patients have been able to safely take this at home. Profits from the sales of this book will assist further research into the use of ketamine for the treatment of depression.