Page 559 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 30 Antidepressant Agents 545

F. Eating Disorders patients are particularly sensitive to the anticholinergic effects of
Bulimia nervosa and anorexia nervosa are potentially devastating the TCAs. On the other hand, the CYP3A4-inhibiting effects
disorders. Bulimia is characterized by episodic intake of large of the SSRI fluvoxamine may make this a problematic choice in
amounts of food (binges) followed by ritualistic purging through some older patients because fluvoxamine may interact with many
emesis, the use of laxatives, or other methods. Medical compli- other medications that an older patient may require. There is some
cations of the purging, such as hypokalemia, are common and suggestion that female patients may respond to and tolerate sero-
dangerous. Anorexia is a disorder in which reduced food intake tonergic better than noradrenergic or TCA antidepressants, but
results in a loss of weight of 15% or more of ideal body weight, the data supporting this gender difference have not been consis-
and the person has a morbid fear of gaining weight and a highly tent. Patients with narrow-angle glaucoma may have an exacerba-
distorted body image. Anorexia is often chronic and may be fatal tion with noradrenergic antidepressants, whereas bupropion and
in 10% or more of cases. other antidepressants are known to lower the seizure threshold in
Antidepressants appear to be helpful in the treatment of buli- epilepsy patients.
mia but not anorexia. Fluoxetine was approved for the treatment At present, SSRIs are the most commonly prescribed first-line
of bulimia in 1996, and other antidepressants have shown benefit agents in the treatment of both MDD and anxiety disorders. Their
in reducing the binge-purge cycle. The primary treatment for popularity comes from their ease of use, tolerability, and safety in
anorexia at this time is refeeding, family therapy, and cognitive overdose. The starting dose of the SSRIs is usually the same as the
behavioral therapy. therapeutic dose for most patients, and so titration may not be
Bupropion may have some benefits in treating obesity. Non- required. In addition, most SSRIs are now generically available
depressed, obese patients treated with bupropion were able to and inexpensive. Other agents, including the SNRIs, bupropion,
lose somewhat more weight and maintain the loss relative to a and mirtazapine, are also reasonable first-line agents for the treat-
similar population treated with placebo. However, the weight loss ment of MDD. Bupropion, mirtazapine, and nefazodone are the
was not robust, and there appear to be more effective options for antidepressants with the least association with sexual side effects
weight loss. and are often prescribed for this reason. However, bupropion is
not thought to be effective in the treatment of the anxiety disor-
G. Other Uses for Antidepressants ders and may be poorly tolerated in anxious patients. The primary
indication for bupropion is in the treatment of major depression,
Antidepressants are used for many other on- and off-label applica- including seasonal (winter) depression. Off-label uses of bupro-
tions. Enuresis in children is an older labeled use for some TCAs, pion include the treatment of attention deficit hyperkinetic disor-
but they are less commonly used now because of their side effects. der (ADHD), and bupropion is commonly combined with other
The SNRI duloxetine is approved in Europe for the treatment of antidepressants to augment therapeutic response. The primary
urinary stress incontinence. Many of the serotonergic antidepres- indication for mirtazapine is in the treatment of major depression.
sants appear to be helpful for treating vasomotor symptoms in However, its strong antihistamine properties have contributed to
perimenopause. Desvenlafaxine is under consideration for FDA its occasional use as a hypnotic and as an adjunctive treatment to
approval for the treatment of these vasomotor symptoms, and more activating antidepressants.
studies have suggested that SSRIs, venlafaxine, and nefazodone The TCAs and MAOIs are now relegated to second- or
may also provide benefit. Although serotonergic antidepressants are third-line treatments for MDD. Both the TCAs and the MAOIs
commonly associated with inducing sexual adverse effects, some are potentially lethal in overdose, require titration to achieve a
of these effects might prove useful for some sexual disorders. For therapeutic dose, have serious drug interactions, and have many
example, SSRIs are known to delay orgasm in some patients. For troublesome adverse effects. As a consequence, their use in the
this reason, SSRIs are sometimes used to treat premature ejacula- treatment of MDD or anxiety is now reserved for patients who
tion. In addition, bupropion has been used to treat sexual adverse have been unresponsive to other agents. Clearly, there are patients
effects associated with SSRI use, although its efficacy for this use whose depression responds only to MAOIs or TCAs. Thus,
has not been consistently demonstrated in controlled trials.
TCAs and MAOIs are probably underused in treatment-resistant
depressed patients.
CHOOSING AN ANTIDEPRESSANT The use of antidepressants outside the treatment of MDD
tends to require specific agents. For example, the TCAs and SNRIs
The choice of an antidepressant depends first on the indication. appear to be useful in the treatment of pain conditions, but other
Not all conditions are equally responsive to all antidepressants. antidepressant classes appear to be far less effective. SSRIs and
However, in the treatment of MDD, it is difficult to demon- the highly serotonergic TCA, clomipramine, are effective in the
strate that one antidepressant is consistently more effective than treatment of OCD, but noradrenergic antidepressants have not
another. Thus, the choice of an antidepressant for the treatment proved to be as helpful for this condition. Bupropion and nortrip-
of depression rests primarily on practical considerations such as tyline have usefulness in the treatment of smoking cessation, but
cost, availability, adverse effects, potential drug interactions, the SSRIs have not been proven useful. Thus, outside the treatment
patient’s history of response or lack thereof, and patient prefer- of depression, the choice of antidepressant is primarily dependent
ence. Other factors such as the patient’s age, gender, and medical on the known benefit of a particular antidepressant or class for a
status may also guide antidepressant selection. For example, older particular indication.