< Table of Contents Table of Contents 2 - Rational Drug Discovery
and SSRIs >
Clinical Pharmacology of SSRI's
1 - Introduction

Why have a book on selective serotonin reuptake inhibitors (SSRIs)? The rationale is simple: This class of antidepressants has become, for many physicians, the treatment of first choice for patients suffering from major depressive illness. The number of prescriptions for SSRIs in the United States equals that of the tricyclic antidepressants (TCAs), which were the gold standard antidepressants for almost 30 years. The widespread acceptance of SSRIs in the United States has occurred in a little over 7 years since the introduction of the SSRI, fluoxetine (Prozac). The introduction of this class has resulted in more than a four-fold increase in the antidepressant market in the United States because physicians are more willing to prescribe these medications to patients due to their greater safety and tolerability coupled with proven efficacy.

This handbook will provide a summary of the clinically relevant pharmacology of SSRIs in a manner that is "user friendly" for the practicing physician. The important similarities and differences will be presented, making liberal use of tables and figures to enhance the book's usefulness as a quick reference for the busy practitioner. The goal is to facilitate the optimum use of this important class of antidepressants.

Specific questions that this book will address include:

  • How was this class of antidepressant drugs developed?
  • What is the presumed mechanism of action (MOA) mediating their antidepressant efficacy?
  • What accounts for their improved safety and tolerability relative to the old "gold standard" TCAs?
  • What are the clinically meaningful differences among members of the SSRI class?
  • What are the factors that the physician should consider when choosing a specific SSRI for a specific patient?

This book will provide a broad overview of the clinical pharmacology of SSRIs in terms of the similarities and differences between SSRIs and TCAs and between different members of the SSRI class. It will focus on studies that permit meaningful comparisons. It is not intended to focus only on the efficacy studies with these drugs, but rather to broadly examine their clinically relevant pharmacology. Since efficacy has been the focus of many other reviews of SSRIs, the data on this topic will be presented in a relatively brief summary form. This book will review how these drugs were developed, providing the foundation for understanding:

  • Class differences between SSRIs and TCAs
  • Class similarities between the SSRIs
  • Pharmacokinetics of the SSRIs
  • Effects of SSRIs on oxidative drug metabolism which are important to physicians since antidepressants are frequently used in combination with other medications by both psychiatric and nonpsychiatric physicians

Whenever possible, data on all five SSRIs marketed worldwide will be presented. However, comparable data does not exist for all the SSRIs on every issue addressed in this book. For example, fixed-dose studies have been published for fluoxetine, paroxetine and sertraline, but not for citalopram and fluvoxamine. In such instances, the data will be provided for the drugs that have published data. The omission and the reason for the omission of the other SSRIs will be noted at each appropriate place in the book.

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