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Biomedical subjects

J H Kocsis

Publications and source records attributed to J H Kocsis.

At least 19 recordsLinked to original sources

Prevalence and comorbidity of dysthymic disorder among psychiatric outpatients.

We investigated prevalence and comorbidity of DSM-III dysthymic disorder in a psychiatric outpatient clinic. Seventy-five consecutive outpatients received structured interviews. Prevalence of dysthymic disorder was 36% in the consecutive sample. Thirty-four dysthymic and 56 non-dysthymic patients were compared for comorbidity. Dysthymic subjects were more likely to meet criteria for major depression, social phobia, and avoidant, self-defeating, dependent, and borderline personality disorders. Dysthymic disorder was usually of early onset, predating comorbid disorders, and had often not received adequate antidepressant treatment. These results help define dysthymic disorder as prevalent, usually predating axis I comorbidity, and associated with particular axis II diagnoses.

Adult

Desipramine treatment of alcoholism.

Depression has been related to relapsed drinking in alcoholics striving to maintain sobriety. Treatment with tricyclic antidepressants might reverse or prevent depressive symptoms related to relapse, and may reverse biochemical abnormalities hypothesized to underlie both depression and alcoholism, thus helping to prolong abstinence in recovering alcoholics. This is a preliminary report of the findings of an ongoing 6-month, double-blind, placebo-controlled trial of desipramine (DMI) in recently abstinent alcoholics, with stratification on the presence or absence of secondary depression and DMI plasma level monitoring. Hypotheses are that DMI will prolong sobriety and reduce depression secondary to alcoholism significantly more than placebo. Subjects were 34 males and 8 females with 19 subjects stratified as depressed after an average of 16.31 days of sobriety. Depressed DMI subjects were significantly less depressed at the time of their termination from study than depressed placebo subjects. No group differences were found in rate of nonsobriety. However, there was a trend for DMI subjects to maintain sobriety for a longer duration on the study since onset of alcoholism, with 33.3 percent depressed placebo, 9.1 percent nondepressed placebo, 60.0 percent depressed DMI, and 41.7 percent nondepressed DMI subjects having their longest period of sobriety on the study.

Adult

Long-term follow-up of chronic depression treated with imipramine.

A long-term follow-up assessment was conducted in 25 chronically depressed patients who had participated in a 6-week trial of imipramine to determine if imipramine responders would sustain a more favorable long-term outcome than nonresponders or noncompleters. Imipramine responders tended to remain on imipramine treatment throughout the follow-up interval and had a significantly better outcome. Eighty-nine percent of the imipramine responders met the criteria for recovery at follow-up compared with 31% in the comparison groups. Imipramine responders also fared significantly better at follow-up on measures of depression, global severity of illness, and social/vocational functioning. The results supported a more favorable long-term outcome in chronic depression patients who had responded to imipramine and suggest that maintenance therapy may be indicated and effective for this disorder.

Adult

Normalization of blunted lymphocyte beta-adrenergic responsivity in melancholic inpatients by a course of electroconvulsive therapy.

Electroconvulsive therapy has been reported to desensitize brain beta-adrenergic receptors in rodents, but this effect has not been studied in man. We examined the effect of a course of electroconvulsive therapy on lymphocyte beta-adrenergic responsivity in 19 inpatients with melancholia. Before treatment, beta-adrenergic cyclic adenosine monophosphate response to isoproterenol was significantly blunted in the patients compared with controls. Following a course of electroconvulsive therapy, beta-adrenergic responsivity increased such that patients no longer differed from controls. Thus, blunted lymphocyte beta-adrenergic responsivity is a state-dependent effect of melancholia that can be corrected by a therapeutic course of electroconvulsive therapy. The effect of electroconvulsive therapy on this beta-adrenergic system is in the opposite direction to that reported for rodent forebrain, where electroconvulsive therapy causes desensitization, and may reflect differences between peripheral and central effects, species differences, or disease effects.

Cyclic AMP

Response to treatment with antidepressants of patients with severe or moderate nonpsychotic depression and of patients with psychotic depression.

Hospitalized patients were divided into nonpsychotic severely depressed (N = 53), nonpsychotic moderately depressed (N = 54), and psychotic depressed (N = 25) groups and treated with either imipramine or amitriptyline, up to 250 mg/day, for 4 weeks. Good response occurred in 39% of the 38 severely depressed, 67% of the 49 moderately depressed, and 32% of the 19 psychotic depressed patients who completed treatment. The response of the patients with nonpsychotic severe depression did not differ significantly from the response of those with psychotic depression, and both groups fared worse than the group with nonpsychotic moderate depression.

Adult

New issues in the prediction of antidepressant response.

Over the past three decades, certain clinical factors have been identified as either positive or negative predictors of response to treatment with the tricyclic antidepressants (TCAs), and have been well reviewed in the psychopharmacology literature. The current report is an effort to focus attention on methodologic and clinical issues that have recently been given attention in this area and that may be useful to clinicians and researchers. The specific issues addressed are (a) the implications of the definitions of "response" in studies of predictive factors, (b) the importance of compliance with treatment, (c) the potentially confounding issues of severity of illness and psychoticism in depression, (d) the status of chronicity of illness as a factor in prediction of treatment response, and (e) the possible value of a definition of "atypical depression" for differential selection of treatment.

Antidepressive Agents

Amoxapine versus amitriptyline for continuation therapy of depression.

The efficacy of continuation therapy with tricyclic antidepressants has been established in a number of controlled trials. This study investigated the efficacy of continuation therapy with a relatively new antidepressant, amoxapine, using a double-blind controlled comparison with amitriptyline. Subjects met DSM-III criteria for major depressive disorder and were randomized to treatment with either amoxapine 400 mg (N = 47) or amitriptyline 300 mg (N = 45). The acute phase lasted up to 8 weeks. Responders were continued on the same drug at the same dose for a 16-week continuation phase. Some measures found more rapid onset for amitriptyline, which is inconsistent with findings from some prior studies. Amitriptyline was more effective in inducing full recovery. There was a trend for higher relapse rates on amoxapine, perhaps related to the fact that there were more partial responders entering continuation therapy from this group. Side effect rates were equivalent in the two drugs. However, physicians rated amoxapine's side effects as more frequently interfering with its therapeutic effect. These data suggest that amoxapine does not offer any clear advantage over amitriptyline for continuation therapy in patients who have major depressive disorder. Of potential clinical relevance is the finding that achieving full recovery in the acute phase may reduce the likelihood of relapse in the continuation phase, regardless of the type of antidepressant medication prescribed.

Adult

A controlled study of the antidepressant efficacy and side effects of (-)-deprenyl. A selective monoamine oxidase inhibitor.

Monoamine oxidase (MAO) inhibitors are effective antidepressants whose use is limited because of unwanted side effects and the possibility of a tyramine-induced hypertensive crisis (cheese reaction). (-)-Deprenyl (the official nonproprietary name for this substance is selegiline), a selective MAO type B inhibitor, may be safer and have fewer side effects, but its antidepressant efficacy is uncertain. A double-blind placebo-controlled study was carried out in depressed outpatients who were treated with (-)-deprenyl in an MAO type B selective dose range and at a higher nonselective dose range. (-)-Deprenyl did not have a statistically significant antidepressant effect after three weeks of treatment at doses of 10 mg/d. However, after six weeks and at higher doses (averaging about 30 mg/d for the second three weeks), (-)-deprenyl was superior to placebo in antidepressant effect with a positive response rate of 50% vs 13.6% and with a 41% reduction in the Hamilton Depression Rating Scale mean score vs 10% in the placebo-treated group. No hypertensive crises were seen. The rate of occurrence of side effects with (-)-deprenyl was no greater than with placebo. It was concluded that (-)-deprenyl is an effective antidepressant in a dose range where it is distinguished by the absence of many of the side effects typical of nonselective MAO inhibitors.

Adult

Blunted beta-adrenergic responsivity of peripheral blood mononuclear cells in endogenous depression. Isoproterenol dose-response studies.

Previous studies of peripheral blood mononuclear cells isolated from drug-free, hospitalized patients with endogenous major depression have demonstrated a diminished adenosine 3',5'-monophosphate (cyclic AMP) response to single concentrations of isoproterenol as compared with that obtained from normal control subjects. We now report results of isoproterenol dose-response studies that indicate lower basal levels of cyclic AMP as well as diminished cyclic AMP levels in response to isoproterenol stimulation at concentrations ranging from 10(-10) to 10(-5) mol/L in drug-free, hospitalized patients with endogenous depression. The major factor responsible for the diminished cyclic AMP production in the depressed patients was a loss of receptor sites capable of cyclic AMP production. Taken together with our previously reported finding that beta-adrenergic antagonist binding was normal in peripheral blood mononuclear cells obtained from depressed patients, the results of the dose-response studies suggest a loss of receptor function (desensitization) rather than a diminished number of receptor binding sites (down-regulation) as the underlying mechanism. Potential explanations for beta-adrenergic desensitization and its implications for the catecholamine hypothesis of depressive disorders are discussed.

Adult

Imipramine treatment for chronic depression.

Antidepressant drugs in the treatment of chronic depressions have received little systematic study. We used a two-week, single-blind placebo washout followed by a six-week, double-blind comparison of imipramine hydrochloride and placebo in a sample of 76 outpatients with DSM-III dysthymic disorder entered into a trial at two centers. Subjects were preponderantly female, had insidious onset at an early age, and had depressions of moderate severity; 96% also met the DSM-III criteria for major depressive disorder at the time of presentation. Sixty percent had a history of persistent depressive symptoms sufficient to meet criteria for major depression for longer than two years. Markedly favorable responses occurred in 45% of imipramine-treated (n = 29) and 12% of placebo-treated (n = 25) patients and, respectively, 59% and 13% of those who completed the study. Imipramine produced significant advantage in measures of depressive symptoms, global severity of illness, and self-rated social and vocational function. Recovered patients experienced remission from both long-standing symptoms and deficits as well as more recently exacerbated aspects of their syndrome. Patients with pure dysthymic disorder of a mild, subsyndromal type were uncommon in these clinical settings. However, anti-depressant medication was effective for many moderately severe chronic depressions, which had previously been untreated or undertreated, presumably related to misdiagnosis.

Adult

Adrenocortical hyperactivity in depression: effects of agitation, delusions, melancholia, and other illness variables.

In an attempt to determine the relative contributions to adrenocortical hyperactivity in depression of agitation, delusions, and melancholic subtype, we measured cortisol levels before and after dexamethasone in 93 unipolar major depressed inpatients. Stepwise multiple regression showed that agitation predicted 22% of the variance in a.m. cortisol level after dexamethasone. Addition of the variables melancholia and delusionality to the regression model accounted for 27% and 34%, respectively, of the variance in the same cortisol variable. Age, illness severity, and weight loss added no further significant predictive value. Age, weight loss, and illness severity did affect cortisol levels when examined separately from the other variables. Rate of nonsuppression on the dexamethasone suppression test (DST) differed between the nonmelancholic major depressive group and any other group with melancholia. These results suggest why some discrepancies may exist between studies of the DST in delusional depression and indicate that agitation merits careful assessment in future studies of DST response.

Adrenal Cortex

Thyroid function in patients maintained on lithium.

To determine the clinical significance of thyroid function abnormalities in patients maintained on lithium, the authors evaluated the relationships of thyroid function tests to clinical response to lithium and side effects from lithium in 20 outpatients meeting DSM-III criteria for major affective disorder. No significant relationships were found between baseline thyroid function tests and clinical response. Thyroxine (T4) and triiodothyronine uptake ratio (T3UR) within the normal range were found to be associated with complaints of lethargy and cognitive impairment. Thirteen subjects were followed prospectively for 6 months with monthly evaluations of affective state, side effects, and occurrence of relapse. Thyroid function tests were repeated at the final visit. Final and mean T3 levels within the normal range were found to be significantly lower in patients who relapsed, and mean T3 level was inversely correlated with affective state as measured by mean scores on the Hamilton Rating Scale for Depression and the Young Mania Rating Scale.

Adult

Imipramine and social-vocational adjustment in chronic depression.

The authors compared the effects of 6 weeks of imipramine treatment with 6 weeks of placebo treatment on social and vocational impairment in chronic depression. Imipramine was associated with significantly greater pre- to posttreatment improvement of social-vocational impairments in chronic depression, suggesting that these impairments may have represented affective symptoms rather than characterologic deficits.

Adult

A critical discussion of DSM-III dysthymic disorder.

The authors review the history of the concept of dysthymia and the literature on the epidemiology, course, and treatment of chronic depression. They present a critical discussion of DSM-III and DSM-III-R criteria for dysthymic disorder. On the basis of this review, they suggest that future revisions of the nomenclature include further subcategorization of chronic depressive disorders and that the term "dysthymic disorder" be reserved for chronic depressive disorders with an insidious onset at an early age. The relationships between dysthymic disorders and personality disorders and the response of subcategories of chronic depression to different treatment modalities need to be researched.

Adult