Alan H. Rosenbaum

Toward a biochemical classification of depressive disorders

Pretreatment urinary MHPG levels were examined in 28 depressed patients as a possible predictor of response to treatment with maprotiline, a tetracyclic antidepressant that exerts potent effects on norepinephrine uptake, but has little effect on serotonin uptake. Maprotiline was administered in doses up to 150 mg/day during the first 2 weeks after which time the dose could be increased incrementally up to 300 mg/day if indicated clinically. At 2 weeks, patients with low pretreatment urinary MHPG levels responded more favorably to treatment than did patients with high MHPG levels. At 4 weeks, patients with low MHPG levels continued to show more favorable responses; however, differences between the two groups were less clear-cut than at 2 weeks. The findings suggest that patients with low pretreatment urinary MHPG levels are more sensitive to, and respond more rapidly to, treatment with maprotiline than patients with high pretreatment urinary MHPG levels.Pretreatment urinary MHPG levels were examined in 28 depressed patients as a possible predictor of response to treatment with maprotiline, a tetracyclic antidepressant that exerts potent effects on norepinephrine uptake, but has little effect on serotonin uptake. Maprotiline was administered in doses up to 150 mg/day during the first 2 weeks after which time the dose could be increased incrementally up to 300 mg/day if indicated clinically. At 2 weeks, patients with low pretreatment urinary MHPG levels responded more favorably to treatment than did patients with high MHPG levels. At 4 weeks, patients with low MHPG levels continued to show more favorable responses; however, differences between the two groups were less clear-cut than at 2 weeks. The findings suggest that patients with low pretreatment urinary MHPG levels are more sensitive to, and respond more rapidly to, treatment with maprotiline than patients with high pretreatment urinary MHPG levels.

Fluoxetine and desipramine in major depressive disorder.

The efficacy and safety of fluoxetine and desipramine were compared in a 6-week double-blind, parallel group study of patients with major depression. Twenty-five were studied while hospitalized for treatment, and 33 were studied as outpatients. Improvement on the Hamilton Rating Scale for Depression was significant for both treatments from week 1 through the end of the study and did not differ between the two treatments at any week. Overall, 64% of fluoxetine-treated patients and 68% of desipramine-treated patients had at least a 50% reduction in Hamilton Depression score. We assessed whether improvement relatively early in treatment was predictive of categorical response at 6 weeks. Among fluoxetine-treated patients, but not desipramine-treated patients, the week 3 change in the Hamilton Depression mood item was significantly predictive of the response at 6 weeks. Patients treated with fluoxetine had significantly fewer side effects than those treated with desipramine. Desipramine, but not fluoxetine, caused a persistent increase in heart rate. The results suggest that early signs of response to fluoxetine are not dependent on achieving steady-state levels of the drug.

Urinary free cortisol levels in anxiety

Abstract Levels of urinary free cortisol (UFC) were determined in 22 patients who met Research Diagnostic Criteria for anxiety disorder (after one week of placebo washout) and in a control group of 22 nonanxious volunteers. Nonsignificant differences were found in the mean cortisol levels, which generally were within normal limits. In this study chronic moderate to severe anxiety did not give rise to hypersecretion and result in high levels of UFC.

Tardive dyskinesia in depressed patients: successful therapy with antidepressants and lithium.

Abstract Depression appears to be common in patients with tardive dyskinesia (TD), and we hypothesized that this refractory movement disorder might respond to antidepressant treatment. We treated 19 TD patients with tricyclic antidepressant therapy supplemented within two to three weeks with lithium carbonate. All patients fulfilled the Research Diagnostic Criteria for major depressive disorder, although seven of them denied being dys phoric. The Abnormal Involuntary Movement Scale and the Hamilton Rating Scale were used to measure dyskinesia and de pression, respectively. Of the 19 patients, 11 (58%) experienced moderate or marked improvement in both dyskinesia and de pression. The authors conclude that treatment with a tricyclic antidepressant and lithium may alleviate tardive dyskinesia in patients with depressive symptoms.

BIOCHEMICAL DISCRIMINATION OF SUBGROUPS OF DEPRESSIVE DISORDERS BASED ON DIFFERENCES IN CATECHOLAMINE METABOLISM

ABSTRACT This paper summarizes the findings of our recent studies which suggest that there may be at least three subtypes of unipolar depressive disorders that can be discriminated, in part, on the basis of differences in urinary levels of 3-methoxy-4-hydroxyphenylglycol (MHPG). A number of different pathophysiological mechanisms that could account for these abnormalities are discussed.