Elaine Tricamo

Social functioning in chronic depression: effect of 6 weeks of antidepressant treatment

Social functioning was assessed in 189 nonmelancholically depressed outpatients. Patients were then treated for 6 weeks in a double-blind trial of phenelzine, imipramine, or placebo and functioning was reassessed. Before treatment, younger, more severely depressed, more chronically depressed patients and those with a DSM-III diagnosis of major depression plus dysthymic disorder were more functionally impaired than patients without these characteristics. Chronically depressed patients who responded to treatment reported significantly improved functioning while nonresponders did not. These results suggest that for some chronically depressed patients, impaired functioning results at least partly from the Axis I mood disorder instead of being entirely attributable to Axis II character pathology.

Adverse Reactions to Monoamine Oxidase Inhibitors. Part II. Treatment Correlates and Clinical Management

From a review of the clinical charts of 198 depressed outpatients, information was extracted on common major treatment emergent side effects associated with phenelzine, tranylcypromine, and imipramine. These included hypertensive reactions, severe orthostatic hypotension, hypomania, significant weight gain, sexual dysfunction, and a residual category of multiple side effects which together culminated in drug discontinuation. In this report, frequency of their occurrence for each drug, level of severity, relation to dose and treatment duration, and physician response at the time the side effect was recorded are described. In addition, procedures found useful in the clinical management of these side effects are discussed.

Adverse reactions to monoamine oxidase inhibitors. Part I. A comparative study.

The incidence of major side effects of phenelzine and tranylcypromine is compared with that of imipramine and placebo medication in depressed outpatients. Psychiatric notes in the charts of 198 patients were reviewed. Based on clinical experience and literature review, 14 side effects were selected for study because of serious medical risk or subjective discomfort great enough to require drug discontinuation. Significant differences in risk for major side effects, as well as distinctive side effect profiles for each drug, were found. More side effects occurred on phenelzine, but these tended not to lead to drug discontinuation more often than with tranylcypromine, nor were they accounted for by differences in age, sex, diagnosis, or duration of treatment.

Predictive Value of Symptoms of Atypical Depression: for Differential Drug Treatment Outcome

Data for 401 depressed outpatients with mood reactivity who participated in a randomized trial comparing placebo, imipramine, and phenelzine were analyzed for predictors of differential response by stepwise multiple regression techniques. Features of the Columbia criteria for atypical depression including oversleeping, overeating, severe anergy, and pathologic rejection sensitivity were each predictive of a poorer response to imipramine than to phenelzine only when compared to those patients with none of the features. These features were not additive in their contribution to differential outcome. Lack of endogenous features was not predictive of a differential drug treatment response. Compared with patients who have no symptoms of atypical depression, patients with any of the four features had an inferior imipramine response rather than a superior phenelzine response. These analyses indicate that the clear differential responsivity to medication treatment in atypical depression is not simply related to any one defining symptom and that further correlates of this apparent biological heterogeneity need to be explored.

A double-blind placebo-controlled comparison of phenelzine and imipramine in the treatment of bulimia in atypical depressives.

Although antidepressants have been found to be superior to placebo in 12 of 14 studies, the relationship between improvement in the depressive diathesis and bulimia is unclear. In this study, the efficacy of placebo, imipramine, and phenelzine is examined in patients comorbid for atypical depression and bulimia. Greater improvement was observed for both depressive and bulimic symptoms with phenelzine than with either imipramine or placebo. Consistent with its poor antidepressant effects in atypical depression, imipramine seemed to have minimal efficacy for the bulimic symptoms of atypical depressives. These data suggest that the presence of bulimia does not alter the treatment response of atypically depressed patients. Furthermore, the data may suggest a link between depression and bulimia in atypical depressives. Demonstrating a statistical difference with a small sample suggests the effect size is robust, however conclusions are limited by a small sample size.

Duration of antidepressant trials: clinical and research implications.

The objective of our study was to demonstrate that additional antidepressant benefit occurs between weeks 4 and 6 in adult outpatients, even when dose is not increased. Response between weeks 4 and 6 was studied among depressed outpatients randomly assigned to imipramine, phenelzine, or placebo under double-blind conditions. Patients were selected for analysis only if they did not have a dose increase after the start of the fourth week of treatment (day 22). Eighty-eight patients met this condition. Conditional probability analysis was performed. Nonresponders to 4 weeks (28 days) of treatment had a significantly greater likelihood of responding by week 6 if they were on phenelzine rather than placebo. The same is probably true for patients on imipramine. In research and clinical care, 4 weeks is too short a trial of phenelzine to conclude a lack of efficacy. Four weeks is probably also too short a trial of imipramine.

Demoralization Predicts Nonresponse to Cognitive Therapy in Depressed Outpatients

Thirty-nine depressed outpatients meeting DSM-III criteria for nonmelancholic major depression or dysthymic disorder were treated with 16 weekly individual cognitive therapy sessions. Prior to treatment, they completed the Beck Depression Inventory, the Hopelessness Scale, and the Dysfunctional Attitudes Scale. Independent of knowledge of outcome, the authors chose from these scales items indicating demoralization, that is, that patients perceived their ability to positively affect their own future as too likely to be ineffectual to warrant efforts at change. After cognitive therapy, 20 patients were considered responders (51%) although three quickly relapsed (44% responded and maintained). Nonresponders had significantly higher pretreatment demoralization scores than did responders. These results suggest that high levels of demoralization may predict poor response of depression to cognitive therapy, although the small sample size precluded differentiation of demoralization from hopelessness.

A comparative study of the electrocardiographic effects of phenelzine, tricyclic antidepressants, mianserin, and placebo.

Although the electrocardiographic effects of the tricyclic antidepressants have been extensively investigated, there are fewer data on the effects of monoamine oxidase inhibitors and tetracyclics on cardiac conduction. This study used high speed recordings of the electrocardiogram to investigate the cardiographic effects of phenelzine and mianserin and to compare these to the effects of imipramine, amitriptyline, and placebo. Phenelzine caused significant slowing of the heart rate, while mianserin showed little effect on heart rate compared to the increases in rate seen with tricyclics. In clinically effective doses, neither phenelzine nor mianserin caused changes in conduction, while both tricyclics studied caused the expected prolongation of conduction. These data suggest that phenelzine and mianserin deserve further study in patients with disease of the cardiac system as they may be less likely to cause heart block in these patients. (J Clin Psychopharmacol 1987;7:335–339)

Phenelzine and imipramine in mood reactive depressives. Further delineation of the syndrome of atypical depression

Sixty patients who met Research Diagnostic Criteria for major, intermittent, or minor depressive disorder and had reactive mood without atypical symptoms were treated with imipramine hydrochloride, phenelzine sulfate, or a placebo. These patients, referred to as simple mood reactive depressives, were contrasted with previously published data from 180 atypical depressives. Atypical depressives had the presence of at least one vegetative atypical sign (hypersomnia, hyperphagia, leaden feeling, or rejection sensitivity) but were otherwise indistinguishable from simple mood reactive depressives. In contrast to the atypical depressives for whom phenelzine was effective and imipramine was relatively ineffective, both medications were equivalently good in simple mood reactive depressives. Since all groups did poorly when given a placebo and well when given phenelzine, the salient feature of atypical symptoms may be that they predict poor response to imipramine. Since the difference between imipramine and placebo depends on the diagnostic group, pharmacologic dissection suggests that atypical symptoms in patients with nonautonomous mood may delineate a qualitatively distinct subgroup.