Antidepressant Drugs

Some scientists believe that depression is caused by insufficient norepinephrine,
serotonin, or dopamine in the synapse. Others theorize that depression
has to do with the number and sensitivity of postsynaptic receptors involved
in the neuron’s response. Drugs for the treatment of depression
come in four major classes: the monoamine oxidase inhibitors (MAOIs),
the tricyclic antidepressants, the selective serotonin reuptake inhibitors
(SSRIs), and “other.” None of these drugs is addictive, although patients
need to be weaned from them slowly to avoid rebound depression or other
adverse effects.
MAOIs were the first modern antidepressants. Monoamine oxidase is an
enzyme that breaks down serotonin, norepinephrine, and dopamine. Inhibiting
the enzyme increases the supply of these neurotransmitters. MAOI
drugs available in the United States include phenelzine and tranylcypromine.
These drugs are not used as commonly as are the other antidepressants,
mostly because of their side effects. However, they are used when
other treatments for depression fail. In addition, they may be used to treat
narcolepsy, phobias, anxiety, and Parkinson’s disease. Common side effects
include drowsiness, fatigue, dry mouth, and dizziness. They may also cause
orthostatic hypotension (a drop in blood pressure when arising) and sexual
dysfunction. Most important, the MAOIs interact with tyramine-containing
foods, such as hard cheese, red wine, and smoked or pickled fish. Consuming
these foods along with an MAOI can cause a hypertensive crisis in
which the patient’s blood pressure rises to potentially deadly levels. Patients
taking MAOIs must also avoid other drugs which stimulate the nervous system
to avoid blood pressure emergencies.
The tricyclic antidepressants were introduced in 1958. They all inhibit
the reuptake of neurotransmitters but differ in which neurotransmitter is
involved. Some affect primarily serotonin, some norepinephrine, and some
work equally on both. Tricyclics commonly available in the United States
include amitriptyline, imipramine, doxepin, desipramine, nortriptyline,
amoxapine, protriptyline, and clomipramine. Primarily used for depression,
these drugs may also be helpful in the treatment of bed-wetting, agoraphobia
(fear of being out in the open) with panic attacks, obsessive-compulsive
personality disorder, chronic pain, nerve pain, and migraine headaches.
An important treatment issue is that it takes two to three weeks of tricyclic therapy before the depressed patient feels much improvement in mood and
energy. During this time, the side effects, which include dry mouth, blurred
vision, constipation, urinary retention, orthostatic hypotension, weight gain,
sexual dysfunction, cardiac problems, and jaundice, tend to be the most
bothersome, leading patients to abandon the treatment before it becomes
effective. Another important treatment issue is that tricyclic antidepressants
are highly lethal in overdose. Some of the tricyclics are highly sedating and
so may be useful in patients who are having difficulty sleeping. On the other
hand, a patient who is already feeling sluggish and sleepy may benefit from a
tricyclic that is less sedating. Any antidepressant may precipitate mania or
hypomania in a patient with a predisposition to bipolar (manic-depressive)
disorder. Elderly patients may be at increased risk for falls or confusion and
memory impairment when taking tricyclics and should be started on very
low doses if a tricyclic is indicated.
The newer selective SSRIs have several advantages over the tricyclics:
They are much less lethal in overdose, are far safer for use among the elderly,
and do not cause weight gain. They work, as the name implies, by decreasing
serotonin reuptake, thereby increasing the amount of neurotransmitter
available at the synapse. Like the tricyclics, SSRIs may need to be
taken for several weeks before a patient notices significant improvement in
mood and energy level. SSRIs available in the United States include fluoxetine
(Prozac), sertraline (Zoloft), fluvoxamine (Luvox), paroxetine (Paxil),
trazodone (Desyral), nafazodone (Serzone), and venlafaxine (Effexor). In
addition to depression, the SSRIs are used for treatment of bulimia nervosa
and obsessive-compulsive disorder. Possible side effects include nausea, diarrhea,
nervousness, insomnia, anxiety, and sexual dysfunction.
Other drugs used in the treatment of depression include mianserin,
maprotiline, and bupropion. The mechanisms by which these drugs work
are not clear, but they may be useful in patients for whom the other antidepressants
do not work or are contraindicated.