Depressive disorders may be either unipolar (depression alone) or bipolar (depression alternating with periods of extreme excitation). The formal diagnosis requires a cluster of symptoms, lasting at least two weeks. These symptoms include, but are not limited to mood changes, insomnia or hypersomnia, and diminished interest in daily activities. The symptoms are not caused by any medical condition, drug side effect, or adverse life event. The condition is severe enough to cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
Secondary depression, depression caused by unfavorable life events, is normally self limiting, and may be best treated with cognitive/behavioral therapy rather than drugs.
Antidepressant agents act by increasing the levels of excitatory neurostransmitters. The main types of antidepressant drugs in use today are:
tetracyclic compounds and atypical antidepressants which do not fall into any of the above categories
Selective serotonin reuptake inhibitors maintain levels of the excitatory neurohormone serotonin in the brain. They do not alter levels of norepinephrine. These have become the drugs of choice for a variety of psychiatric disorders, primarily because of their low incidence of severe side effects as compared with other drugs in this therapeutic class. SSRIs show similar actions and side effect profiles, but may vary in duration of action.
Tricyclic compounds, identified by their chemical structure containing three carbon rings, are an older class of antidepressants. Although generally effective, they have a high incidence of anticholinergic effects, notably dry mouth and dry eyes, which can cause discomfort. They also cause cardiac arrythmias. Because tricyclics act on both serotonin and norepinephrine, they may have some value in treatment of patients who fail to respond to SSRIs. Drugs in this class are often available at low prices, which may be significant when cost is a major factor in treatment. They have also been found useful in control of some neurologic pain syndromes.
Tricyclic antidepressants are similar, but may vary in severity of side effects, most notably the degree of sedation and the extent of the anticholinergic effects.
Tetracyclic compounds and atypical antidepressants are chemically distinct from both the major groups and each other. Although maprotilene (no brand name, marketed in generic form only) and mirtazepine (Remeron) are similar in chemical structures, they differ in their balance of activity on serotonine and norepinephrine levels.
Monoamine oxidase inhibitors (phenelzine [Nardil], tranylcypromine [Parnate]) have largely been supplanted
in therapy because of their high risk of severe adverse effects, most notably severe hypertension. They act by inhibiting the enzyme monoamine oxidase, which is responsible for the metabolism of the stimulatory neurohormones norepinephrine, epinephrine, dopamine, and serotonin. The MAOIs are normally reserved for patients who are resistant to safer drugs. Two drugs, eldepryl (Carbex, used in treatment of Parkinson's disease) and the herb, St. John's wort, have some action against monoamine oxidase B, and have shown some value as anti-depressants. They do not share the same risks as the non-selective MAO inhibitors.
All antidepressant agents, regardless of their structure, have a slow onset of action, typically three to five weeks. Although adverse effects may be seen as early as the first dose, significant therapeutic improvement is always delayed. Similarly, the effects of antidepressants will continue for a similar length of time after the drugs have been discontinued.
Samuel Uretsky PharmD, The Gale Group Inc., Gale, Detroit,