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First-Generation Versus Second-Generation Antipsychotics in Adults: Comparative Effectiveness [Internet]

First-Generation Versus Second-Generation Antipsychotics in Adults: Comparative Effectiveness [Internet]

Comparative Effectiveness Reviews - Agency for Healthcare Research and Quality (US)

Version: August 2012

Executive Summary

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.,

Summary and Discussion

This report provides a comprehensive synthesis of the evidence on the comparative effectiveness and safety of first- (FGAs) versus second-generation antipsychotics (SGAs) in adults with schizophrenia, schizophrenia-related psychoses, and bipolar disorder. We included studies that directly compared one FGA versus one SGA. We did not include: studies comparing various FGAs or those comparing various SGAs; trials with no active comparator (e.g., no treatment or placebo-controlled trials); or those trials comparing antipsychotics not approved by the U.S. Food and Drug Administration (FDA) or no longer available in the U.S. (Appendix O). The strength of evidence (SoE) for core illness symptoms and key adverse events (AEs) is summarized by comparison in the tables below.

Results

This chapter reports on the results of our literature review and synthesis. First, we describe the results of our literature search and selection process. Description of the characteristics and methodological quality of the studies follow. For Key Questions (KQs) 1, 2, 4, and 5, we present the results of our analysis separately for schizophrenia and bipolar disorder and then by comparison. The findings for KQ3 are presented at the end of this section and are organized by comparison across both conditions. The results of all meta-analyses, including sample sizes, effect estimates, 95% confidence intervals (CI), and I-squared (I2) statistics, are available in evidence tables for each comparison.

Introduction

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 multi-acting receptor-targeted antipsychotics, whereas SGAs have been categorized according to their pharmacological properties as dopamine partial agonists. There is ongoing research testing these proposed mechanisms of action within each class with respect to the neurobiology of different psychiatric disorders.,

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