|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
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
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.