Severe Major Depression

SYMPTOMS       TREATMENTS       DEPRESSIVE DISORDER       AROMATHERAPY

Severe depression is, by and large, a recurrent -- not a constant -- illness. There are approximately 10 million people in the United States who suffer from the disorder and tend to alternate between valleys of despair and hopelessness and peaks of normal or near-normal mood. Scientists conducting a nationwide study now report, however, that about one-fifth of a group of patients who sought treatment for undoing depression at several university medical centers do not have periods of emotional calm; they remain severely depressed for at least two years despite being given antidepressant drugs or electroconvulsive therapy (ECT).

Severe depression is a distinct clinical entity that has not been well studied. Definitions of severe depression have not been standardized across clinical trials, which have included hospitalized patients, outpatients, patients with endogenous depression, and melancholic subtype. Response rates to antidepressant therapy  have generally been lower in patients with severe depression than in less ill patients, and aggressive dosing should be considered along with more prolonged courses of treatment.

Treating until patients achieve a 50% reduction in the HAM-D is debatable as a useful end point for clinical research. However, in the severely depressed patient, this does not usually represent a clinically relevant response to treatment.

Ideally, all depressed patients should be treated until they are well and have attained a euthymic state (e.g., HAM-D scores  7), but in severely depressed patients this may require longer and more intense trials. Also, use of a single treatment modality may not be effective in these patients; electroconvulsive therapy, combination antidepressant therapy, or the addition of an antipsychotic agent in patients with delusional depression frequently should be considered.

Although there may be lingering questions among some physicians about the effectiveness of SSRIs in the treatment of severe depression, the composite findings of the studies assessed in this review are compelling. In 13 of the 15 controlled studies evaluated, the SSRIs, paroxetine, fluoxetine, sertraline, and fluvoxamine, were as effective as comparator TCAs in outpatients or hospitalized patients with severe depression or melancholia. Only two studies reported SSRIs to be less effective.

In one study, fluvoxamine was significantly more effective than imipramine. Moreover, the SSRIs are generally well tolerated compared with the TCAs, particularly at the doses needed to achieve a response in severe depression. A 16th study found venlafaxine to be superior to fluoxetine. Thus, a preponderance of data suggests that the SSRIs are as effective as, but better tolerated than, the TCAs in the severely depressed patient.

One caveat to consider, however, is that most of these studies were relatively short term (i.e., 6 weeks), and additional improvement would probably have been noted had the treatment been extended to 8 or 12 weeks, or longer.

Further study is clearly needed to help sufferers get rid of depression , and a double-blind, random-assignment trial of melancholic patients that compares an SSRI with a TCA dosed to maintain therapeutic plasma concentrations for an adequate time period would best substantiate these observations.