The World Health Organization defines depression as a primary contributor to the global burden of disease and predicts it will become the second leading cause of death by 2020. The need to develop effective therapies has never been so pressing. Current antidepressant drugs have several limitations. This 2010 book looks at the future of mood-disorder research, covering the identification of new therapeutic targets, establishing new preclinical models, new medicinal chemistry opportunities, and fostering greater understanding of genetic influences. These strategies are likely to help build a better picture of the disease process, and lead to new opportunities for patient stratification and treatment. The ultimate goal for this strand of research is to develop more personalized and effective treatments for this chronic and debilitating condition. This is essential reading for all those involved in psychopharmacologic drug development, and mental health clinicians seeking a preview of discoveries soon to influence their practice.

The future of mood-disorder research: covering identification of new therapeutic targets, preclinical models, and medicinal chemistry opportunities.

The Advances in Pharmacology series presents a variety of chapters from the best authors in the field. - Includes the authority and expertise of leading contributors in pharmacology - Presents the latest release in the Advances in Pharmacology series

In recent years, there have been major developments in the fields of pharmacogenetics and pharmacogenomics, with the potential to make drug treatments in psychiatric medicine more effective. However, improvements in drug efficacy and tolerability, as well as finding the optimal dosage, can only be realized if in vivo mechanisms of drug action and ADME (absorption, distribution, metabolism, excretion) processes (pharmacokinetics) of psychopharmacological agents are better understood. In this volume, current progress and perspectives in pharmacogenetic testing of drug-metabolizing enzymes, drug transporters and other drug targets involved in the response to psychotropic agents are described extensively. This provides a timely overview of what has been achieved in the area of psychiatric pharmacogenomics alongside some promising directions and perspectives for future research.Psychiatrists, general medical doctors as well as pharmacologists and clinical pharmacologists will find new insights into the development and applications of pharmacogenomics in psychiatry.

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

Every day millions of people take psychiatric drugs. In Better Than Prozac Samuel Barondes considers the benefits and limitations of Prozac, Ritalin, Valium, Risperdal, and other widely used medications and the ways that superior ones are being created. In tracing the early history of these drugs Barondes describes the accidental observations that led to their discovery and their great impact on our view of mental illness. He goes on to show how their unexpected therapeutic effects were attributed to their influence on neurotransmitters that carry signals in the brain and how this guided their improvement. But Barondes reminds us that, like the originals, current psychiatric drugs don't always work, and often have negative side effects. Furthermore, none were crafted as remedies for known brain abnormalities. In contrast, the design of the drugs of the future will be based on a different approach: an understanding of the molecular mechanisms that give rise to specific patterns of mental symptoms. Using colorful examples of contemporary research, he shows how it is gradually leading to a new generation of psychiatric medications. A lucid evaluation of psychopharmacology, Better Than Prozac offers a deep understanding of psychiatric drugs for people who take them, those who are considering them, and those who are just fascinated by the powerful effects of these simple chemicals on our thoughts and our feelings.

Fluoxetine, best known by the trade name Prozac®, unlike other psychotropic drugs whose effects were serendipitously stumbled upon, was the first developed for a precise mechanism of action, that is, the ability to selectively inhibit serotonin reuptake, based upon the theory that increasing the availability of serotonin would treat major depression. Once approved by the FDA in 1987, fluoxetine quickly became the most prescribed psychotropic drug worldwide and its success in improving mood disorders has triggered the development of a large number of congener molecules, commonly known as SSRIs after their purported mechanism of action. However, a quarter of a century after its development, the idea that fluoxetine asserts its positive behavioral effect through inhibition of serotonergic reuptake is not firmly established. This book reviews several preclinical and clinical reports suggesting that the pharmacological effects of fluoxetine may be mediated by means other than the regulation of serotonin, including the regulation of gene expression, modifying epigenetic mechanisms as well as modifying microRNAs. One of the most prominent mechanisms for the therapeutic relevance of fluoxetine relates to influencing neuroplasticity by enhancing neurotropic factors, including BDNF signaling and altering adult neurogenesis. The ability of fluoxetine to rapidly increase neurosteroid levels accounts for the fast anxiolytic effects of this drug. Fluoxetine action at sigma-1 receptor or modulating glutamatergic neurotransmission as well as the combination of fluoxetine with other psychotropic drugs is discussed in relation to its therapeutic effects. While fluoxetine was primarily prescribed as an antidepressant, this drug currently represents a treatment of choice for a broad spectrum of psychiatric disorders, including post-traumatic stress disorder and a range of anxiety disorders. This drug even possesses analgesic actions and is a valuable therapy for stroke. This book also highlights emerging evidence on the gender-specific effects of fluoxetine, its potential adverse features, including its addiction liability in combination with psychostimulants, and the impact of perinatal fluoxetine exposure.

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.

A compelling and troubling exploration of a generation raised on antidepressants, and a book that combines expansive interviews with substantive research-based reporting, Coming of Age on Zoloft is a vitally important and immediately engrossing study of one of America’s most pressing and omnipresent issues: our growing reliance on prescription drugs. Katherine Sharpe, the former editor of Seed magazine’s ScienceBlogs.com, addresses the questions that millions of young men and women are struggling with. “Where does my personality end and my prescription begin?” “Do I have a disease?” “Can I get better on my own?” Combining stout scientific acumen with first-person experience gained through her own struggle with antidepressants, Sharpe leads the reader through a complex subject, a guide towards a clearer future for all.

Personalized Psychiatry presents the first book to explore this novel field of biological psychiatry that covers both basic science research and its translational applications. The book conceptualizes personalized psychiatry and provides state-of-the-art knowledge on biological and neuroscience methodologies, all while integrating clinical phenomenology relevant to personalized psychiatry and discussing important principles and potential models. It is essential reading for advanced students and neuroscience and psychiatry researchers who are investigating the prevention and treatment of mental disorders. - Combines neurobiology with basic science methodologies in genomics, epigenomics and transcriptomics - Demonstrates how the statistical modeling of interacting biological and clinical information could transform the future of psychiatry - Addresses fundamental questions and requirements for personalized psychiatry from a basic research and translational perspective