Page 558 - Basic _ Clinical Pharmacology ( PDFDrive )

544 SECTION V Drugs That Act in the Central Nervous System

they have had two or more serious MDD episodes in the previous PTSD is manifested when a traumatic or life-threatening event
5 years or three or more serious episodes in a lifetime. results in intrusive anxiety-provoking thoughts or imagery, hypervigi-
It is not clear whether antidepressants are useful for all subtypes lance, nightmares, and avoidance of situations that remind the patient
of depression. For example, patients with bipolar depression may of the trauma. SSRIs are considered first-line treatment for PTSD and
not benefit much from antidepressants even when added to mood can benefit a number of symptoms including anxious thoughts and
stabilizers. In fact, the antidepressants are sometimes associated hypervigilance. Other treatments, including psychotherapeutic inter-
with switches into mania or more rapid cycling. There has also ventions, are usually required in addition to antidepressants.
been some debate about the overall efficacy of antidepressants
in unipolar depression, with some meta-analyses showing large C. Pain Disorders
effects and others showing more modest effects. Although this Antidepressants possess analgesic properties independent of their
debate is not likely to be settled immediately, there is little debate mood effects. TCAs have been used in the treatment of neuro-
that antidepressants have important benefits for most patients. pathic and other pain conditions since the 1960s. Medications
Psychotherapeutic interventions such as cognitive behavioral that possess both norepinephrine and 5-HT reuptake blocking
therapy appear to be as effective as antidepressant treatment for properties are often useful in treating pain disorders. Ascending
mild to moderate forms of depression. However, cognitive behav- corticospinal monoamine pathways appear to be important in the
ioral therapy tends to take longer to be effective and is generally endogenous analgesic system. In addition, chronic pain conditions
more expensive than antidepressant treatment. Psychotherapy is are commonly associated with major depression. TCAs continue
often combined with antidepressant treatment, and the combina- to be commonly used for some of these conditions, and SNRIs
tion appears more effective than either strategy alone. are increasingly used. In 2010, duloxetine was approved for the
treatment of chronic joint and muscle pain. As mentioned earlier,
B. Anxiety Disorders milnacipran is approved for the treatment of fibromyalgia in the
After major depression, anxiety disorders represent the most USA and for MDD in other countries. Other SNRIs, eg, desven-
common application of antidepressants. A number of SSRIs and lafaxine, are being investigated for a variety of pain conditions
SNRIs have been approved for all the major anxiety disorders, from postherpetic neuralgia to chronic back pain.
including PTSD, OCD, social anxiety disorder, GAD, and panic
disorder. Panic disorder is characterized by recurrent episodes of D. Premenstrual Dysphoric Disorder
brief overwhelming anxiety, which often occur without a precipi- Approximately 5% of women in the child-bearing years will have
tant. Patients may begin to fear having an attack, or they avoid prominent mood and physical symptoms during the late luteal
situations in which they might have an attack. In contrast, GAD is phase of almost every cycle; these may include anxiety, depressed
characterized by a chronic, free-floating anxiety and undue worry mood, irritability, insomnia, fatigue, and a variety of other physical
that tends to be chronic in nature. Although older antidepressants symptoms. These symptoms are more severe than those typically
and drugs of the sedative-hypnotic class are still occasionally used seen in premenstrual syndrome (PMS) and can be quite disruptive
for the treatment of anxiety disorders, SSRIs and SNRIs have to vocational and interpersonal activities. The SSRIs are known
largely replaced them. to be beneficial to many women with PMDD, and fluoxetine and
The benzodiazepines (see Chapter 22) provide much more sertraline are approved for this indication. Treating for 2 weeks out
rapid relief of both generalized anxiety and panic than do any of of the month in the luteal phase may be as effective as continuous
the antidepressants. However, the antidepressants appear to be treatment. The rapid effects of SSRIs in PMDD may be associated
at least as effective as, and perhaps more effective than, benzo- with rapid increases in pregnenolone levels.
diazepines in the long-term treatment of these anxiety disorders.
Furthermore, antidepressants do not carry the risks of dependence E. Smoking Cessation
and tolerance that may occur with the benzodiazepines. Bupropion was approved in 1997 as a treatment for smoking
OCD is known to respond to serotonergic antidepressants. It cessation. Approximately twice as many people treated with
is characterized by repetitive anxiety-provoking thoughts (obses- bupropion as with placebo have a reduced urge to smoke. In
sions) or repetitive behaviors aimed at reducing anxiety (com- addition, patients taking bupropion appear to experience fewer
pulsions). Clomipramine and several of the SSRIs are approved mood symptoms and possibly less weight gain while withdraw-
for the treatment of OCD, and they are moderately effective. ing from nicotine dependence. Bupropion appears to be about as
Behavior therapy is usually combined with the antidepressant for effective as nicotine patches in smoking cessation. The mechanism
additional benefits. by which bupropion is helpful in this application is unknown,
Social anxiety disorder is an uncommonly diagnosed but a but the drug may mimic nicotine’s effects on dopamine and
fairly common condition in which patients experience severe norepinephrine and may antagonize nicotinic receptors. Nicotine
anxiety in social interactions. This anxiety may limit their ability is also known to have antidepressant effects in some people, and
to function adequately in their jobs or interpersonal relationships. bupropion may substitute for this effect.
Several SSRIs and venlafaxine are approved for the treatment of Other antidepressants may also have a role in the treatment of
social anxiety. The efficacy of the SSRIs in the treatment of social smoking cessation. Nortriptyline has been shown to be helpful in
anxiety is greater in some studies than their efficacy in the treat- smoking cessation, but the effects have not been as consistent as
ment of MDD. those seen with bupropion.