Depression - pathology & drug used.

 How to treat depression

Depression is one of the most common psychiatric disorders. Currently about 5-6% of the population is depressed , and an estimate 10% of people may become depressed during their lives (lifetime prevalence).

The symptoms of depression are often subtle and unrecognized both by
patients and physicians. Patients with vague complaints that resist explanation as manifestations of somatic disorders and those who might be simplistically described as "neurotic" should be suspected of being
Depressed.
Depression is a heterogeneous disorder that has been characterized and classified in various ways.
According to the American Psychiatric Associations fourth edition (1994) of the Diagnostic and Statistical Manual of mental disorders, several diagnosis of affected disorder are possible. Major depression and dysthymia (minor) are pure depressive syndrome, whereas bipolar disorder and cyclothymic disorder signify depression in association with mania.

A simplified classification based on presumed origin is as follows:
 (1) reactive or "secondary" depression (most common), occurring in response to real stimuli such as grief, ill-ness, etc
 (2) "endogenous" depression, a genetically
determined biochemical disorder manifested by inability to experience ordinary pleasure or to cope with ordinary life events
 (3) depression associated with bi-polar affective (manic-depressive) disorder.

An intensive effort to formalize guidelines for the treatment of depression is provided by the cross-disciplinary publication of the Depression Guideline Panel(1993) and its update on newer pharmacotherapies
(Mulrow et al, 1999). Pharmacologic treatment is emphasized, though a continung role for electroconvulsive therapy for delusional or severe forms of life-threatening depression is noted.
Despite intensive research,the mechanisms of action of various pharmacologic
treatments are still not understood, though most are believed to involve eftects on two monoamine neuro-transmitters: serotonin and norepinephrine.

Soon after the introduction of reserpine in the early 1950s, it became apparent that the drug could induce depression in patients being treated for hypertension and schizophrenia as well as in normal subjects. Within the next few years, Pharmacologic studies revealed that. The principal mechanism of action of reserpine was to
inhibit the storage of amine neuro- transmitters such as serotonin and norepinephrine in the vesicles of
presynaptic nerve endings. Reserpine induced depression and depleted stores of amine neurotransmitters, therefore, it
was reasoned, depression must be associated with.
Decreased functional amine-dependent synaptic transmission. This idea provided the basis for the amine hypothesis of depression.

 A major puzzle in applying this hypothesis was the fact that although the pharmacologic actions of both tricyclic and MAO inhibitor classes of antidepressants are prompt, the clinical eftects require weeks to become manifest. Attempts have been made to explain this observation by involving slow compensatory responses
to the initial blockade of amine reuptake or MAO inhibition.While the amine hypothesis is undoubtedly too simplistic, It has provided the major experimental models
for the discovery of new antidepressant drugs. As a result, all the currently available antidepressant drugs except bupropion are classified as having their primary actions on the metabolism, reuptake, or selective receptor antagonism of serotonin, norepinephrine, or both.