DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Drug Therapy of Depression and
Anxiety Disorders
James M. O’Donnell and
Richard C. Shelton
Depression and anxiety disorders are the most common
mental illnesses, each affecting in excess of 10-15% of
the population at some time in their lives. Both anxiety
and depressive disorders are amenable to pharmacological
treatments that have been developed since the
1950s. With the discovery of more selective and safer
drugs, the use of antidepressants and anxiolytics has
moved from the domain of psychiatry to other medical
specialties, including primary care. The relative safety
of the majority of commonly used antidepressants and
anxiolytics notwithstanding, their optimal use requires
a clear understanding of their mechanisms of action,
pharmacokinetics, potential drug interactions, and the
differential diagnosis of psychiatric illnesses.
A confluence of symptoms of depression and anxiety
may affect an individual patient; some of the drugs
discussed here are effective in treating both disorders,
suggesting common underlying mechanisms of pathophysiology
and response to pharmacotherapy. In large
measure, our current understanding of pathophysiological
mechanisms underlying depression and anxiety has
been inferred from the mechanisms of action of psychopharmacological
compounds (Chapter 14). While
depression and anxiety disorders comprise a wide range
of symptoms, including changes in mood, behavior,
somatic function, and cognition, some progress has been
made in developing animal models that respond with
some sensitivity and selectivity to antidepressant or anxiolytic
drugs (Cryan and Holmes, 2005; Miller et al.,
2010 ). Recent work has focused on identifying endophenotypes
associated with psychiatric diseases, with the
goals of understanding their underlying pathophysiology
and targeting them pharmacologically (Cannon and
Keller, 2006). Although animal models are useful for
investigating pharmacological mechanisms of action and
providing initial evidence of efficacy, the development
of antidepressant and anxiolytic drugs depends on
clinical trials. However, it is not uncommon for psychopharmacological
agents to fail to show efficacy in
clinical trials; in large measure this is due to significant
placebo effects and the lack of objective and firm end
points. In spite of these limitations, the last half century
has seen notable advances in the discovery and development
of drugs for treating depression and anxiety.
CHARACTERIZATION OF DEPRESSIVE
AND ANXIETY DISORDER
Symptoms of Depression
Depression, in general, is classified as major depression
(i.e., unipolar depression) or bipolar depression (i.e.,
manic depressive illness); bipolar depression and its
treatment are discussed in Chapter 16. Lifetime risk of
unipolar depression is ~15%. Females are affected twice
as frequently as males (Kessler et al., 1994). Depressive
episodes are characterized by depressed or sad mood,
pessimistic worry, diminished interest in normal activities,
mental slowing and poor concentration, insomnia or
increased sleep, significant weight loss or gain due to
altered eating and activity patterns, psychomotor agitation
or retardation, feelings of guilt and worthlessness,
decreased energy and libido, and suicidal ideation, occurring
most days for a period of at least 2 weeks. In some
cases, the primary complaint of patients involves somatic
pain or other physical symptoms and can present a diagnostic
challenge for primary care physicians. Depressive
symptoms also can occur secondary to other illnesses
such as hypothyroidism, Parkinson’s disease, and
inflammatory conditions. Further, depression often complicates
the management of other medical conditions
(e.g., severe trauma, cancer, diabetes, and cardiovascular