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A J Gelenberg

Publications and source records attributed to A J Gelenberg.

At least 37 records · Page 2Linked to original sources
PubMed1998

Maintenance phase efficacy of sertraline for chronic depression: a randomized controlled trial.

CONTEXT: The chronic form of major depression is associated with a high rate of prevalence and disability, but no controlled research has examined the impact of long-term treatment on the course and burden of illness. OBJECTIVE: To determine if maintenance therapy with sertraline hydrochloride can effectively prevent recurrence of depression in the high-risk group of patients experiencing chronic major depression or major depression with antecedent dysthymic disorder ("double depression"). DESIGN: A 76-week randomized, double-blind, parallel-group study, conducted from September 1993 to November 1996. SETTING: Outpatient psychiatric clinics at 10 academic medical centers and 2 clinical research centers. INTERVENTION: Maintenance treatment with either sertraline hydrochloride (n = 77) in flexible doses up to 200 mg or placebo (n = 84). PATIENTS: A total of 161 outpatients with chronic major or double depression who responded to sertraline in a 12-week, double-blind, acute-phase treatment trial and continued to have a satisfactory therapeutic response during a subsequent 4-month continuation phase. MAIN OUTCOME MEASURE: Time to recurrence of major depression. RESULTS: Sertraline afforded significantly greater prophylaxis against recurrence than did placebo (5 [6%] of 77 in the sertraline group vs 19 [23%] of 84 in the placebo group; P = .002 for the log-rank test of time-to-recurrence distributions). Clinically significant depressive symptoms reemerged in 20 (26%) of 77 patients treated with sertraline vs 42 (50%) of 84 patients who received placebo (P = .001). With use of a Cox proportional hazards model, patients receiving placebo were 4.07 times more likely (95% CI, 1.51-10.95; P = .005) to experience a depression recurrence, after adjustment for study site, type of depression, and randomization strata. CONCLUSIONS: Maintenance therapy with sertraline is well tolerated and has significant efficacy in preventing recurrence or reemergence of depression in chronically depressed patients.

Adult↗
PubMed1998

Knowing our limits.

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Antidepressive Agents↗
PubMed1998

The treatment of chronic depression, part 2: a double-blind, randomized trial of sertraline and imipramine.

BACKGROUND: Chronic depression appears to be a common, frequently disabling illness that is often inadequately treated. Unlike episodic depressions with shorter illness duration, neither acute nor long-term treatment approaches for chronic depression have been well studied. METHOD: 635 outpatients at 12 sites who met DSM-III-R criteria for chronic major depression or double depression were randomly assigned to 12 weeks of double-blind treatment with either sertraline (in daily doses of 50-200 mg) or imipramine (in daily doses of 50-300 mg). Efficacy and safety were assessed either weekly or every 2 weeks during the 12 weeks of acute treatment. RESULTS: Despite high rates of chronicity (mean duration of major depression = 8.9+/-9.1 years; mean duration of dysthymia = 23+/-13 years) and high rates of comorbidity, 52% of patients achieved a satisfactory therapeutic response to sertraline or imipramine (by a conservative, intent-to-treat analysis). Approximately 21% of the patients who had achieved a therapeutic response at week 12 had not done so at week 8, confirming the longer time to response in depressions with high chronicity. Patients treated with sertraline reported significantly fewer adverse events and were significantly less likely to discontinue treatment due to side effects than imipramine-treated patients (6.3% vs. 12.0%). CONCLUSION: These results indicate that patients suffering from depression with high chronicity can achieve a good therapeutic response to acute treatment with either sertraline or imipramine, although sertraline is better tolerated.

Adult↗
PubMed1998

The treatment of chronic depression, part 1: study design and rationale for evaluating the comparative efficacy of sertraline and imipramine as acute, crossover, continuation, and maintenance phase therapies.

BACKGROUND: Chronic depressions are common, disabling, and undertreated, and prior chronicity predicts future chronicity. However, few studies directly inform the acute or maintenance phase treatments of chronic depressions and even less is known about the effects of treatment on psychosocial functioning. METHOD: We describe the design and rationale for 2 parallel double-blind, randomized, multicenter acute and maintenance phase treatment trials. One focused on DSM-III-R major depression currently in a chronic (> or = 2 years) major depressive episode, the other on DSM-III-R major depression with concurrent DSM-III-R dysthymia ("double depression"). RESULTS: Considering the critical knowledge deficits, we designed a 12-week acute phase safety and efficacy trial of sertraline versus imipramine, followed by a 16-week continuation treatment phase for subjects with a satisfactory therapeutic response. Patients receiving sertraline who successfully completed the continuation phase entered a 76-week maintenance trial to compare sertraline with placebo; those taking imipramine continued without a placebo substitution. As part of the acute trial, subjects completing but failing to respond to the initial 12-week acute phase medication were crossed over (double-blind) to the alternative medication for a 12-week acute phase trial. We obtained naturalistic follow-up data (up to 18 months) for subjects exiting the protocol at any time. CONCLUSION: Multiphase protocols for chronic depression can test efficacy by randomized contrasts as well as shed light on key clinical issues such as the degree of response or attrition expected at particular times in a trial or the preferred medication sequence in a potential multistep treatment program.

Antidepressive Agents, Tricyclic↗
PubMed1997

Pindolol augmentation of treatment-resistant depressed patients.

BACKGROUND: Recent uncontrolled reports describe a dramatic and rapid improvement of depressive symptoms in patients treated with the combination of pindolol and serotonin selective reuptake inhibitors or monoamine oxidase inhibitors. The present study attempts to replicate those findings. METHOD: Ten outpatients with current DSM-III-R major depressive disorder who had failed to obtain or maintain an appropriate response to an adequate trial of antidepressant drug were included in a randomized double-blind, placebo-controlled, crossover study. Subjects received pindolol 2.5 mg p.o. t.i.d. or placebo for 2 weeks in addition to their current antidepressant. Clinical monitoring, vital signs, and behavioral ratings were performed weekly for the duration of the study. RESULTS: Pindolol was well tolerated by all patients. None of the subjects experienced significant symptom worsening during the addition of either placebo or active drug. At the end of the 2-week trial, there was no statistically significant difference between pindolol augmentation and placebo. Two patients had a categorical response during placebo treatment. No categorical responses were observed during pindolol augmentation. CONCLUSION: This study failed to replicate the rapid and dramatic response to pindolol augmentation in treatment-resistant depressed patients.

Adrenergic beta-Antagonists↗
PubMed1996

Serum lithium levels and psychosocial function in patients with bipolar I disorder.

OBJECTIVE: This study compared the effect of two different serum lithium levels on the psychosocial functioning of patients with bipolar I disorder. METHOD: Ninety patients with bipolar I disorder were enrolled in a prospective, double-blind, maintenance trial of lithium. The patients were randomly assigned to treatment with doses of lithium adjusted to achieve a serum lithium concentration of either 0.8 to 1.0 mmol/liter (standard) or 0.4 to 0.6 mmol/liter (low). The Longitudinal Interval Follow-Up Evaluation was used to assess psychosocial functioning in the areas of work, interpersonal relationships, and global functioning. All observed values were analyzed with a mixed-effects analysis of covariance. Independent variables included treatment group (low or standard lithium serum level), relapse status, socioeconomic status, time from random treatment assignment to assessment, termination of protocol before or after relapse, length of remission before random treatment assignment, polarity of the last mood episode before random treatment assignment, and number of mood episodes in the 3 years before random treatment assignment. RESULTS: Relapse was associated with large negative effects on psychosocial functioning. Patients in higher socioeconomic brackets had better psychosocial functioning than did those in lower brackets. Patients receiving lithium doses that achieved standard serum levels had better psychosocial functioning than those receiving doses that achieved low serum levels; this effect was partially but not wholly mediated through relapse prevention. CONCLUSIONS: For patients with bipolar I disorder, standard serum lithium levels may enhance psychosocial functioning, above and beyond the effects of relapse prevention.

Adolescent↗
PubMed1996

Antipsychotics in bipolar disorder.

Antipsychotics are commonly added to lithium for relief of severe psychotic symptoms and behavioral disruption during an acute manic episode. In general, lithium is superior in stabilizing mood and ideation, whereas neuroleptics are better in controlling hyperactivity, and the course of clinical response is faster to antipsychotics than to lithium. The effects of neuroleptics on bipolar depression need further study. Traditional neuroleptics carry the risk of extrapyramidal symptoms, and concern exists over neurotoxicity from the combination of lithium and a neuroleptic. Roles for clozapine, risperidone, and newer atypical neuroleptics, which may carry a lower risk of associated extrapyramidal side effects, will become clear with additional study and clinical experience. Long-term antipsychotic therapy in the maintenance phase of bipolar disorder is common; the efficacy, however, remains unclear and the risk of tardive movement disorders is substantial. Otherwise treatment-resistant patients who receive maintenance antipsychotic therapy to prevent recurrent episodes of mania should be followed closely, with regular screening for early signs of movement disorders.

Acute Disease↗
PubMed1995

Lithium tremor.

BACKGROUND: Tremor is a common problem for patients taking lithium, but little is known about its true prevalence, its effect on compliance, and effective treatments. METHOD: The data base of the Lithium Information Center in Madison, Wis., was searched for articles relating to lithium tremor. RESULTS: Studies show a wide range of incidence of lithium tremor--4% to 65%--due to differences in defining and reporting this side effect. While lithium tremor often decreases with time on lithium, other treatment options include changing the dose or preparation of lithium, decreasing or eliminating other drugs, and treating with beta-blocking drugs, primidone, fatty acids, or potassium. Severe tremor may be a sign of lithium toxicity. CONCLUSION: Patients should be evaluated for lithium tremor on a regular basis. Diagnostic criteria should be standardized by a double-blind, random assignment, multicenter study that could also investigate proposed treatments.

Adrenergic beta-Antagonists↗
PubMed1994

Treatment of bipolar disorder: how far have we come?

Research on bipolar disorder continues to indicate that recurrent episodes of mania and depression have a deteriorative effect on patient functioning, response to treatment, and prognosis. Lithium is the treatment of choice for both acute affective episodes and long-term maintenance, but not all patients respond adequately to lithium therapy. Alternatives or adjuncts to lithium in acute mania include carbamazepine, valproate, electroconvulsive therapy (ECT), and clozapine. For acute depression, antidepressants often are added to lithium treatment or used alone; nonpharmacologic options include ECT and light therapy. Studies suggest that carbamazepine and valproate may be as effective as lithium in maintenance therapy and that thyroid supplementation may increase response in rapid-cycling patients. Using psychosocial intervention in addition to maintenance pharmacologic treatment may increase medication compliance, decrease hospitalizations, and increase overall functioning.

Antimanic Agents↗
PubMed1993

Report on efficacy of treatments for bipolar disorder.

Nearly one percent of adults in the United States suffer from bipolar disorder, a severe, chronic, and life-threatening disease. This disorder involves periodic episodes of mania and depression. At least 80 percent of patients who have an initial episode of mania will have one or more subsequent episodes. Because recurring episodes have a cumulative deteriorative effect on functioning and treatment response, the sooner bipolar patients are diagnosed and treated, the better their changes are for recovery. With optimal treatment, a bipolar patient can regain approximately 7 years of life, 10 years of effective major activity, and 9 years of normal health, which otherwise would have been lost due to the illness. For treatment purposes, bipolar disorder is divided into three stages: acute mania, acute depression, and maintenance. Lithium is the standard treatment for acute mania, and its effectiveness is solidly supported by experimental evidence. Rigorous studies over the past 40 years involving hundreds of patients have repeatedly shown the efficacy of lithium therapy, with approximately 80 percent of subjects responding favorably. For those who do not, several other drugs and nonpharmacologic therapies are available that have shown high success rates in well-standardized trials. The anticonvulsant drug carbamazepine has been associated with improved symptoms in approximately 60 percent to 70 percent of subjects in double-blind trials comparing it against placebo, neuroleptics, and/or lithium. Valproate, another anticonvulsant, has been shown to be comparable to lithium and superior to placebo in treating acute mania in several double-blind, placebo-controlled trials. Electroconvulsive therapy (ECT) is another effective treatment for acute mania, with a positive response rate of approximately 80 percent. Acute bipolar depression has been successfully treated with a number of agents, including monoamine oxidase inhibitors (e.g., tranylcypromine), lithium, tricyclic antidepressants, and second-generation antidepressants (e.g., bupropion). Nonpharmacologic approaches such as ECT, sleep deprivation, and light therapy have been effective as supplemental therapy in many patients. For maintenance therapy, lithium is again the drug of choice. Clinical research has shown that maintenance lithium lessens the frequency and severity of episodes of mania and depression in bipolar patients and helps stabilize mood between episodes. Long-term lithium treatment also reduces the risk of mortality for bipolar patients: without treatment, mortality is two to three times higher than that of the general population; with treatment, it is not significantly different. Several other drugs have been studied as alternatives or adjuncts to lithium therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Bipolar Disorder↗
PubMed1993

Monoamines and the mechanism of antidepressant action: effects of catecholamine depletion on mood of patients treated with antidepressants.

Brain catecholamines can be rapidly reduced by inhibiting their synthesis with alpha-methyl-para-tyrosine (AMPT). In order to assess the role of catecholamines in antidepressant action AMPT challenges were administered in a double-blind, placebo-controlled, crossover fashion to 14 depressed patients having maintained a therapeutic antidepressant response for > or = 2 weeks (3 desipramine, 2 mazindol, 5 fluoxetine, 4 sertraline). Each patient participated in two challenges one week apart. Each challenge included a baseline, two days of either AMPT or diphenhydramine (active placebo), and a followup. Antidepressant drugs were continued throughout testing. The 3 desipramine- and 2 mazindol-responders had a rapid increase in depression score during AMPT but not placebo (diphenhydramine) challenge whereas only 1 of 9 selective serotonin reuptake inhibitor (SSRI)-treated patients did. The implication of this is that the antidepressant response to desipramine may be more acutely dependent on brain catecholamine content than the response to SSRIs. In the context of our previous work with tryptophan depletion, these results suggest that the neurobiological mechanisms underlying the antidepressant responses to different drugs involve alterations in the functioning of different neurotransmitter systems and reinforce the importance of changes in both the serotonin and catecholamine systems for successful antidepressant responses.

Adult↗
PubMed1993

Psychiatry 2013.

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Forecasting↗
PubMed1993

Postmarketing surveillance: perspectives of a journal editor.

In the absence of a systematic monitoring program for drugs newly approved by the Food and Drug Administration (FDA), reports in clinical journals provide a legitimate forum for disseminating information about unexpected pharmacologic events. A journal editor bears the responsibility for publishing educated clinical observations that meet standards of scientific rigor while not giving premature credibility to chance and dubious reports of side effects of new drugs. Often this responsibility involves overcoming the fear of bad publicity and withstanding pressures from pharmaceutical companies to print only positive information about new products. Published preliminary observations may contribute to the problem of product liability, but they also generate testable hypotheses and healthy debate. If hypotheses later prove to be incorrect, they can be refuted by systematic studies and clarified in reviews and editorials. Our goal of effective education will be reached not by self-censorship but by scientific openness.

Humans↗