Tricyclic antidepressants (TCAs), so-called because they have three rings in their chemical structure, work in the brain by making certain that the neurotransmitter norepinephrine (NE) and, to a lesser extent, serotonin (SE), remain in the synapse between nerve fibers rather than being taken back up into the nerve cell itself. The end result of this is that the amount of neurotransmitter in the synapse increases, thereby allowing the flow of nerve impulses to return to normal. This is associated with an antidepressant response in the patient.
First-generation tricyclics include:
* the first TCA, imipramine (Tofranil), which was introduced in 1958
* amitriptyline (Elavil)
* desipramine (Norpramin)
* nortriptyline (Pamelor)
* protriptyline (Vivactjl)
* clomipramine (Anafranil)
* trimipramine (Surmontil)
* the European medication amineptine (Survector).
Although side effects vary from drug to drug and person to person, the side effects generally associated with TCAs include dry mouth, constipation, blurred vision, weight gain, an increased heart rate, drowsiness, urinary retention, memory problems, impotence, decreased blood pressure and dizziness when standing up. It generally takes between 7 and IS days before the drug begins to have an antidepressant effect.
Related medications called tetracyclics include maprotiline (Ludiomil), amoxapine (Asendin), and the European drug mianserin (Bolvidon).
Monoamine oxidase inhibitors (MAOIs) work by preventing the breakdown of the neurotransmitter hormones norepinephrine and serotonin, which in turn has the effect of increasing the amount of those substances in the synapses.
MAOIs include:
o isocarboxazid (Marplan)
o phenelzine (Nardil)
Besides such side effects as restlessness, dizziness, and weight gain, MAOIs have one unique problem. You have to be very careful what you eat while taking an MAOI. Ordinary foods that contain tyramine including—but not limited to—cheese, Chianti wine, yogurt, lima beans, pickled herring, smoked meats, liver, and large amounts of caffeine or chocolate can trigger a sudden rise in blood pressure that has been known to cause blood vessels in the brain to burst, the so-called cheese effect A stroke or even death can be the outcome. A related MAOl is the European drug Deprenyl, which is marketed in the United States as an anti-Parkinson drug, not an antidepressant It requires less attention to dietary restriction.
Selective serotonin reuptake inhibitors (SSRIs) block the uptake only of serotonin, thereby causing it to increase in the nerve synapse. SSRIs include:
* fluoxetine (Prozac)
* sertraline (Zoloft)
* paroxetine (Paxil)
* fluvoxamine (Luvox)
* nefazadone (Serzone)
* citalopram (under development in U.S., available in Europe as Lipramil or Seropram).
These drugs relieve depression as effectively as the TCAs and MAOIs, but their side effect profile is considerably milder.
Lithium, although primarily used as a mood stabilizer with manic-depressive disorders, can also play an important prophylactic role in recurrent unipolar depression and even a therapeutic role in major depression when it is added to an antidepressant as a step-up treatment. It comes in these generic forms under various trade names:
o lithium carbonate; slow-release lithium carbonate
o lithium citrate syrup (liquid).
Structurally unrelated compounds used for the treatment of depression include a number of other medications, such as:
* trazodone (Deseryl)
* buproprion (Wellbutrin)
* venlafaxine (Effexor).
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