First Generation Versus Second Generation Antipsychotics In Adults Comparative Effectiveness

Antipsychotic medications are used to treat and manage symptoms for several psychiatric disorders and are commonly categorized into two classes. First-generation antipsychotics (FGAs), also known as “typical antipsychotics,” were developed in the 1950s. Second-generation antipsychotics (SGAs), also known as “atypical antipsychotics,” emerged in the 1980s. To date, FGAs have been classified according to their chemical structure, which includes serotonin-dopamine antagonists and multiacting receptor-targeted antipsychotics, whereas SGAs have been categorized according to their pharmacological properties as dopamine partial agonists. There is ongoing research testing the proposed mechanisms of action within each class with respect to the neurobiology of different psychiatric disorders. According to findings from the 2004–05 Medical Expenditure Panel Survey, an estimated 2 million adult patients in the U.S. were prescribed an antipsychotic medication, three quarters of whom were taking an SGA. In 2003, an estimated $2.82 billion were spent in the country on these medications, with SGAs accounting for 93% of this expenditure. Today, 20 FGAs and SGAs are commercially available in the U.S. and approved by the FDA. Individuals taking antipsychotics may stop taking their medication for a number of reasons, including adverse events (AEs) and a lack of improvement in their symptoms. As a result, ongoing evaluations of drug efficacy and models of patient decisionmaking are essential. This Review provides a comprehensive synthesis of the evidence examining the benefits and harms associated with the use of FDA-approved FGAs and SGAs. This CER focuses on comparisons of individual medications rather than drug classes. This topic is important and timely, given the ongoing debate about the comparative benefits and harms of FGAs and SGAs. The focus of this report complements other recent reviews investigating different SGAs, the off-label use of antipsychotics, and FGAs versus SGAs in the pediatric population. The focus of this report is adults age 18 to 64 years with schizophrenia, schizophrenia-related psychoses, and bipolar disorder. The following Key Questions were investigated in the report: 1. For adults (age 18 to 64 years) with schizophrenia, schizophrenia-related psychoses, or bipolar disorder, what are the comparative efficacy and effectiveness of FGAs versus SGAs for improving core illness symptoms? 2. For adults (age 18 to 64 years) with schizophrenia, schizophrenia-related psychoses, or bipolar disorder, what is the comparative effectiveness of FGAs versus SGAs for improving functional outcomes and decreasing health care system utilization? 3. For adults (age 18 to 64 years) with schizophrenia, schizophrenia-related psychoses, or bipolar disorder, do FGAs and SGAs differ in medication-associated AEs and safety? 4. For adults (age 18 to 64 years) with schizophrenia, schizophrenia-related psychoses, or bipolar disorder, what is the comparative effectiveness of FGAs versus SGAs for the following other outcomes: Relapse and remission rates, Medication adherence and persistent use, Patient insight into illness, Health-related quality of life, Patient satisfaction, Comorbidity: endpoints of victimization, homelessness, and substance abuse, Patient-reported outcomes, Ability to obtain and retain employment and succeed in job duties, Concomitant use of other medications, especially those used to treat EPS, and Patient preferences. 5. For adults (age 18 to 64 years) with schizophrenia, schizophrenia-related psychoses, or bipolar disorder, what are the comparative effectiveness and risks of FGAs versus SGAs in subgroups defined by the following variables? Disorder subtypes, Sex, Age group (18–35 years, 36–54 years, and 55–64 years), Race, Comorbidities, Drug dosage, Follow up period, Treatment of a first episode versus treatment in the context of previous episodes (previous exposure to antipsychotics), and Treatment resistance.

Antipsychotic Long-acting Injections (LAIs) were introduced in the 1960s to improve treatment adherence in schizophrenia. Subsequently, first-generation antipsychotic LAIs became widely used in many countries. Since the initial publication of Antipsychotic Long-acting Injections in 2010, new trial data have been published on long-acting injection (LAI) preparations of the drugs Risperidone, Paliperidone, and Olanzapine. Furthermore, a new LAI preparation of the drug Aripiprazole has recently been approved for clinical use in the United States and is likely to be approved in Europe soon. The second edition of this successful book has been fully updated to include this new data, with reference to both observational studies and randomized controlled trials, as well as other new developments in the clinical use of antipsychotic LAIs. New chapters have been added covering the comparison between oral and injectable antipsychotics, Olanzapine LAI, Aripiprazole LAI, and the practicalities of organizing a specialized clinic for long-acting injectable antipsychotics. Existing chapters have also been thoroughly updated to take into account the most recently published research. Antipsychotic Long-acting Injections, Second edition brings together clinical and research findings on LAIs in a comprehensive volume, with chapters written by international experts.

This resource includes individual chapters on the phenomenology, pathogenesis, pharmacotherapy and psychotherapy of OCD and other related disorders, and features fully updated content and research, as well as a resources chapter, and an appendix with summaries of the major rating scales used to assess patients with OCD.

The guideline offers clear, concise, and actionable recommendation statements to help clinicians to incorporate recommendations into clinical practice, with the goal of improving quality of care. Each recommendation is given a rating that reflects the level of confidence that potential benefits of an intervention outweigh potential harms.

Presents a user-friendly step-by-step manual on the psychotropic drugs prescribed for children and adolescents by clinicians and nurse practitioners.

The new edition of this popular handbook has been thoroughly updated to include the latest data concerning treatment of first-episode patients. Drawing from their experience, the authors discuss the presentation and assessment of the first psychotic episode and review the appropriate use of antipsychotic agents and psychosocial approaches in effective management. This is an authoritative text written by a team of highly respected authors for psychiatrists, neurologists, primary care practitioners and health care professional working in psychiatry. Drawing from their experience, the presentation and assessment of the first psychotic episode are discussed, details regarding antipsychotic drugs and their appropriate use are reviewed and psychosocial approaches are examined. The resulting book offers a concise and valuable guide to those wishing to review the latest proposals for the treatment of first-episode psychosis supported by up-to-date references, in a single publication.

Six decades after the serendipitous discovery of chlorpromazine as an antipsychotic and four decades after the launch of clozapine, the first atypical or second generation antipsychotic, psychopharmacology has arrived at an important crossroad. It is clear that pharmacological research and pharmaceutical development must now focus on complementary or even alternative mechanisms of action to address unmet medical needs, i.e. poorly treated domains of schizophrenia, improved acceptance by patients, better adherence to medication, safety in psychoses in demented patients, and avoiding cardiac and metabolic adverse effects. The first completely novel mechanisms evolving from our insights into the pathophysiology of psychotic disorders, especially the role of glutamatergic mechanisms in schizophrenia, are now under development, and further principles are on the horizon. This situation, in many respects similar to that when the initial second-generation antipsychotics became available, can be rewarding for all. Preclinical and clinical researchers now have the opportunity to confirm their hypotheses and the pharmaceutical industry may be able to develop really novel classes of therapeutics. When we were approached by the publishers of the Handbook of Experimental Pharmacology to prepare a new volume on antipsychotics, our intention was to capture both, the accumulated preclinical and clinical knowledge about current antipsychotics as well as prospects for new and potentially more specific antischizophrenia principles. These efforts should be based on the pathophysiology of the diseases and the affected neurotransmitter systems. Since preclinical research on antipsychotic compounds is only reliable when intimately linked through translational aspects to clinical results, we decided to include clinical science as well. It turned out that that this endeavor could not be covered by a single volume. We thank the editorial board and the publishers for supporting our decision to prepare two volumes: Current Antipsychotics and Novel Antischizophrenia Treatments. These topics cannot really be separated from one another and should be seen as a composite entity despite the somewhat arbitrary separation of contributions into two volumes. The continuing challenges of developing improved and safer antipsychotic medications remain of concern and are discussed in the first volume. The new opportunities for the field to develop and license adjunctive treatments for the negative symptoms and cognitive deficits that are treated inadequately by existing compounds have been incentivized recently and provide the focus for the second volume. We hope these collective contributions will facilitate the development of improved treatments for the full range of symptomatology seen in the group of schizophrenias and other major psychotic disorders. Gerhard Gross, Ludwigshafen, Germany Mark A. Geyer, La Jolla, CA This volume will try to put current therapy - achievements, shortcomings, remaining medical needs - and emerging new targets into the context of increasing knowledge regarding the genetic and neurodevelopmental contributions to the pathophysiology of schizophrenia. Some of the chapters will also deal with respective experimental and clinical methodology, biomarkers, and translational aspects of drug development. Non-schizophrenia indications will be covered to some extent, but not exhaustively.