Lithium prophylaxis of bipolar illness. The value of combination treatment.

Using a longitudinal life-table analysis, we assessed the efficacy of lithium alone, administered within the context of a naturalistic clinical setting, by calculating the probability of patients remaining free of an affective episode (manic or depressive) over a five-year course. In addition, for those who suffered a manic or depressive relapse, we attempted to analyse the subsequent course of patients who suffered a manic/hypomanic or depressive relapse and were then restabilised on lithium plus either a neuroleptic, carbamazepine, or a benzodiazepine, or lithium plus an antidepressant. Lithium alone offered an average 83% probability against an affective relapse after one year, 52% after three years, and 37% after five years. For patients who failed on lithium alone, it appeared that combination treatment offered greater protection against subsequent affective relapse than the initial course on lithium alone.

Melancholic/endogenous depression and response to somatic treatment and placebo.

OBJECTIVE: The authors' goals were to examine the effects of somatic treatment and placebo in patients with and without endogenous/melancholic depression. METHOD: Before entry into one of four trials of antidepressant drugs versus placebo, 231 patients were assessed as to whether they met Research Diagnostic Criteria for definite endogenous depression and/or DSM-III criteria for major depressive episode with melancholia. These patients were prospectively assessed for subsequent response to antidepressant treatment or placebo. Previous studies of the effect of endogenous/melancholic depression on treatment response were also reviewed. RESULTS: Of the 76 patients with DSM-III melancholia given active medication, 41 (54%) had a complete or partial response, but only 10 (23%) of the 44 patients with melancholia given placebo had a complete or partial response. Of the 76 depressed patients without melancholia given active medication, 46 (61%) had a complete or partial response, and 15 (43%) of the 35 depressed patients without melancholia given placebo had a complete or partial response. Moderately depressed patients with DSM-III melancholia had a significantly better response to active medication than did severely depressed patients with melancholia and showed the greatest difference between response to active medication and response to placebo. The results of the review of previous studies of the effect of endogenous/melancholic depression on treatment response were mixed. CONCLUSIONS: Depressed patients with melancholia were not particularly different from depressed patients without melancholia in their responses to antidepressant medication but did differ from patients without melancholia in their responses to active medication versus placebo, particularly if their depression was moderate and not severe. This suggests that patients with DSM-III melancholia may be unresponsive to nonsomatic treatments.

Personality traits and response to desipramine.

We attempted to prospectively examine the effects of personality traits in 68 acutely depressed patients treated with desipramine over 4-5 weeks to assess whether the presence or absence of these traits played a role in response to antidepressant treatment. Overall the 39 responders had statistically significantly lower cluster III personality trait scores than non-responders, and a trend toward lower cluster I and cluster II scores. We then followed the 39 desipramine responders for up to 6 months on the dose to which they responded in accordance with standard clinical practice. Overall 23 of the 39 sustained their initial improvement, with eight relapsing and eight dropping out between 5 weeks and 6 months. When comparing these three groups with the 29 initial non-responders, those who sustained the 6-month response had statistically significantly lower cluster II, cluster III, and total personality scores than initial responders who relapsed, initial responders who dropped out and did not complete 6 months of treatment, and initial non-responders.

Relationship of dose to antidepressant prophylactic efficacy.

We studied 75 patients on prophylactic antidepressants (imipramine or amitriptyline) to examine the effect of antidepressant dose on long-term prophylaxis of depression and to see whether lowering the dose during the prophylactic period affected subsequent relapse. There was no statistically significant difference in maintenance and prophylactic doses between the group that completed the 2 years free of a depressive episode, the group that had a depressive relapse and the group that dropped out of treatment before the end of the prophylactic period. However, the group that completed the 2 years free of a depressive episode had significantly less of a difference between the maintenance and prophylactic doses than the other 2 groups. Overall, 11/31 who remained on the same dose during the prophylactic period vs the maintenance period relapsed vs 17/25 who had their dose lowered during the prophylactic period vs the maintenance period. The difference was statistically significant.

The prophylactic efficacy of tricyclic antidepressants--a five year followup.

1. In order to evaluate the efficacy of antidepressants in the prevention of recurrent depression, a longitudinal life-table analysis was carried out involving 217 unipolar patients whose depressive symptoms had remitted following treatment with one of five standard tricyclics (imipramine, amitriptyline, desipramine, nortriptyline, and doxepin). 2. Following six months continued euthymic mood these patients were maintained on the medication to which they initially responded to in a clinical setting over a 5 year period. These patients were compared against a group of 28 individuals who were treated acutely for their depression and responded to one of the above the 5 standard antidepressants, but following 5-6 months continuation treatment were taken off the antidepressant at their own request. 3. Though there was a lower rate of relapse in patients receiving active medication vs the no treatment group, the frequency of relapse was high for the group on active drug. 4. Using the longitudinal life-table method of Fleiss there was a pessimistic-optimistic average relapse rate of 30%, 50%, and 60%, at 1, 2, and 3 years respectively while on active drug vs a 51%, 74%, and 83% relapse rate on no treatment. Overall 87 of 217 patients on active drug (40.1%) were observed to have suffered a depressive relapse over the 5 year course.