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Biomedical subjects

Mark Hyman Rapaport

Publications and source records attributed to Mark Hyman Rapaport.

13 recordsLinked to original sources
PubMed2006

Effects of risperidone augmentation in patients with treatment-resistant depression: Results of open-label treatment followed by double-blind continuation.

Approximately one-third of persons with depression do not respond to antidepressant monotherapy. Studies suggest that atypical antipsychotic augmentation may benefit these patients. We investigated the longer-term efficacy of risperidone augmentation of serotonin-selective reuptake inhibitor treatment for resistant depression. In 57 in- and outpatient centers in three countries, we conducted a three-phase study with 4-6 weeks of open-label citalopram monotherapy, 4-6 weeks of open-label risperidone augmentation, and a 24-week double-blind, placebo-controlled discontinuation phase. A total of 489 patients with major depressive disorder and 1-3 documented treatment failures entered the citalopram monotherapy phase (20-60 mg/day). Patients with <50% reduction in HAM-D-17 scores entered the risperidone augmentation phase (0.25-2.0 mg/day). Patients with HAM-D-17< or =7 or CGI-S < or = 2 were randomized to risperidone or placebo augmentation. The primary outcome was time to relapse during the double-blind phase. During citalopram monotherapy, 434 patients had <50% HAM-D-17 reduction; 299 (68.9%) were fully nonresponsive (<25% reduction) and 135 were partially nonresponsive (25-49% reduction). Of the 386 nonresponders who entered the augmentation phase, 243 remitted and 241 entered the double-blind phase. Median time to relapse was 102 days with risperidone augmentation and 85 days with placebo (NS); relapse rates were 53.3 and 54.6%, respectively. In a post hoc analysis of patients fully nonresponsive to citalopram monotherapy, median time to relapse was 97 days with risperidone augmentation and 56 with placebo (p = 0.05); relapse rates were 56.1 and 64.1%, respectively (p < or = 0.05). Open-label risperidone augmentation substantially enhanced response in treatment-resistant patients, but the longer-term benefits of augmentation were not demonstrated in this study.

Adolescent↗
PubMed2006

Classification and treatment of sub-threshold depression.

PURPOSE OF REVIEW: The purpose of this review is to evaluate the recent literature on depressive spectrum disorders. RECENT FINDINGS: Research into so-called 'minor' forms of depression has moved beyond efforts justifying these entities and describing their components to an exploration of the impact of depressive spectrum disorders on health, quality of life, and as a predisposing factor for major depressive disorder. As with major depression, pharmacological and psychosocial interventions may be useful treatments. Researchers have begun to examine the nature of depressive spectrum disorders in specific populations, such as the elderly and the medically ill. SUMMARY: Sub-threshold forms of depression are becoming a focus of research at a time when quality of life and prevention of serious mental illness are being recognized as important public health concerns. Individuals with depressive spectrum disorders are at an increased risk of developing major depressive disorder and are more likely to have a history of episodes of depression. The challenges confronting psychiatric researchers include developing a consensus about diagnosis of depressive spectrum disorders and ways to measure their severity, and increasing public recognition of the impact of the entire spectrum of depression in order to facilitate the discovery of appropriate treatments.

Depressive Disorder↗
PubMed2005

The effects of celecoxib augmentation on cytokine levels in schizophrenia.

Celecoxib augmentation therapy has been reported to enhance the rate of clinical response for patients with schizophrenia. This may be due in part to an effect of celecoxib in the immune dysfunction associated with schizophrenia. Given concerns about the safety of COX-2 inhibitors, studies investigating cytokine levels in medicated patients with schizophrenia are of public health importance. Twenty-eight schizophrenia subjects stabilized on olanzapine or risperidone were randomized to receive 8 wk of celecoxib (400 mg/d) or placebo. Serum soluble IL-2 receptor (sIL-2r) and in-vitro PHA-stimulated whole-blood cytokine production levels were measured at baseline, 1 wk, and 8 wk. Celecoxib augmentation did not alter any of the cytokine parameters measured for the overall study group. However, 1 wk of celecoxib augmentation increased TNF-alpha and IL-2 production levels in olanzapine-treated subjects. These elevations did not persist by week 8. Overall, celecoxib does not significantly modify cytokine levels in medicated schizophrenia subjects.

Adult↗
PubMed2005

Celecoxib augmentation of continuously ill patients with schizophrenia.

BACKGROUND: Previous reports have demonstrated a beneficial effect of celecoxib adjunctive therapy for patients with an acute exacerbation of schizophrenia. We investigated the effects of celecoxib augmentation of atypical antipsychotic medications for continuously symptomatic outpatient subjects with schizophrenia to further extend these findings. We hypothesized that celecoxib augmentation therapy would improve psychopathology ratings compared with placebo. METHODS: Thirty-eight symptomatic outpatient subjects meeting DSM-IV criteria for schizophrenia and on a stable dose of an atypical antipsychotic medication for at least three months were randomized to receive 8 weeks of double blind placebo or celecoxib (400 mg/day) augmentation. Measures of psychopathology, functional disability, and extrapyramidal side effects were performed throughout the study. RESULTS: The treatment cohorts did not differ on any of the clinical outcome measures. CONCLUSIONS: Celecoxib augmentation of continuously ill outpatient subjects with schizophrenia did not improve clinical symptoms or measures of disability.

Adult↗
PubMed2005

Quality-of-life impairment in depressive and anxiety disorders.

OBJECTIVE: Previous reports demonstrating quality-of-life impairment in anxiety and affective disorders have relied upon epidemiological samples or relatively small clinical studies. Administration of the same quality-of-life scale, the Quality of Life Enjoyment and Satisfaction Questionnaire, to subjects entering multiple large-scale trials for depression and anxiety disorders allowed us to compare the impact of these disorders on quality of life. METHOD: Baseline Quality of Life Enjoyment and Satisfaction Questionnaire, demographic, and clinical data from 11 treatment trials, including studies of major depressive disorder, chronic/double depression, dysthymic disorder, panic disorder, obsessive-compulsive disorder (OCD), social phobia, premenstrual dysphoric disorder, and posttraumatic stress disorder (PTSD) were analyzed. RESULTS: The proportion of patients with clinically severe impairment (two or more standard deviations below the community norm) in quality of life varied with different diagnoses: major depressive disorder (63%), chronic/double depression (85%), dysthymic disorder (56%), panic disorder (20%), OCD (26%), social phobia (21%), premenstrual dysphoric disorder (31%), and PTSD (59%). Regression analyses conducted for each disorder suggested that illness-specific symptom scales were significantly associated with baseline quality of life but explained only a small to modest proportion of the variance in Quality of Life Enjoyment and Satisfaction Questionnaire scores. CONCLUSIONS: Subjects with affective or anxiety disorders who enter clinical trials have significant quality-of-life impairment, although the degree of dysfunction varies. Diagnostic-specific symptom measures explained only a small proportion of the variance in quality of life, suggesting that an individual's perception of quality of life is an additional factor that should be part of a complete assessment.

Adult↗
PubMed2004

Randomized, placebo-controlled trial of fluoxetine for acute treatment of minor depressive disorder.

OBJECTIVE: Minor depressive disorder is both common and associated with significant psychosocial impairment. This study examined antidepressant treatment efficacy in a large group of patients with minor depressive disorder. METHOD: One hundred sixty-two patients with minor depressive disorder were randomly assigned to receive fluoxetine or placebo in a 12-week, double-blind study; 73% (59 of 81) of the patients in each treatment group completed the study. Patients were evaluated weekly with standard depression rating instruments and measures of psychosocial impairment. Hypotheses were tested by last-observation-carried-forward analysis of variance (ANOVA) and confirmed by mixed (random-effects) regression analysis. RESULTS: At baseline, minor depressive disorder patients were mildly to moderately depressed, with a corresponding degree of functional impairment. Over 12 weeks of treatment, both ANOVA and mixed regression showed fluoxetine to be superior to placebo as indicated by significantly greater improvement of fluoxetine-treated patients in scores on the 30-item clinician-rated Inventory of Depressive Symptomatology, the 17-item and 21-item Hamilton Depression Rating Scale, the Beck Depression Inventory, and the Clinical Global Impression severity scale. Improvement in Global Assessment of Functioning Scale score was significantly greater for the fluoxetine group in mixed regression analysis only. Patients in both treatment groups reported a similar number and severity of adverse events during the 12-week treatment period. CONCLUSIONS: Clinicians frequently encounter minor depressive disorder either as a prodromal or residual phase of illness in major depressive disorder or as de novo minor depressive disorder episodes. Fluoxetine is significantly superior to placebo in reducing minor depressive disorder symptoms within a 12-week period. Improvement in psychosocial function with fluoxetine may take longer than 12 weeks.

Adaptation, Psychological↗
PubMed2004

Escitalopram continuation treatment prevents relapse of depressive episodes.

BACKGROUND: Current guidelines for antidepressant use recommend 4 to 6 months of continuation treatment to prevent relapse of depression following symptom resolution. This study evaluates the efficacy and safety of continuation escitalopram treatment. METHOD: Outpatients diagnosed with DSM-IV major depressive disorder (male or female, aged 18 to 81 years) who had completed 8 weeks of randomized double-blind treatment with escitalopram, citalopram, or placebo entered an 8-week flexible-dose, open-label phase in which all patients received escitalopram (10-20 mg/day). This study was initiated November 3, 1999, and completed April 5, 2001. Patients who met responder criteria (score of < or = 12 on the Montgomery-Asberg Depression Rating Scale [MADRS]) were randomly assigned in a 2:1 ratio to escitalopram (at the dose each patient was receiving at the end of the open-label phase) or placebo for 36 weeks of double-blind treatment. The primary efficacy variable was time to depression relapse (defined as MADRS score > or = 22 or discontinuation due to an insufficient therapeutic response) from the start of the double-blind treatment phase. RESULTS: A total of 502 patients received open-label escitalopram treatment and had at least 1 MADRS assessment. A total of 274 evaluable subjects entered the double-blind treatment phase; 93 received placebo and 181 received escitalopram. Time to depression relapse was significantly longer (p =.013) and the cumulative rate of relapse was significantly lower in patients who received escitalopram (26% escitalopram vs. 40% placebo; hazard ratio = 0.56; p =.01). Escitalopram-treated subjects had significantly lower depression ratings than those of placebo-treated patients. Escitalopram continuation treatment was safe and well tolerated. Discontinuation rates due to adverse events were 7% for the placebo group and 4% for the escitalopram-treated group. CONCLUSION: Continuation treatment with escitalopram is effective in preventing relapse into an episode of major depressive disorder.

Administration, Oral↗
PubMed2003

Studies characterizing 60 kda autoantibodies in subjects with schizophrenia.

BACKGROUND: Studies suggest that schizophrenic patients have an increased prevalence of serum antibodies to neuroblastoma cell proteins migrating at 60 kilodaltons (kDa). We present work identifying and characterizing 60 kDa antigen-antibody interactions. METHODS: Sera from schizophrenic subjects and normal volunteers were screened by Western blotting. Proteins migrating at 60 kDa were characterized by two-dimensional gel electrophoresis and indirect immunofluorescent staining of human epithelial cell (HEp-2) slides. Human brain and bladder cell complementary deoxyribonucleic acid libraries were screened with immunoaffinity-purified antibodies. Complementary deoxyribonucleic acid clones were sequenced and compared with published databases. Proteins were generated by in vitro transcription/translation and expression in an Escherichia coli BL21 system. Immunoprecipitation and immunohistochemistry studies were performed. RESULTS: Fifteen percent (17/117) of schizophrenic subjects and 3% (2/62) of normal volunteers had autoantibodies that reacted with 60 kDa proteins [chi(2)(1) = 4.4, p =.037]. Five percent of subjects had autoantibodies directed against 60 kDa heat shock protein (HSP60) [chi(2)(1) = 3.3, p =.100). Two-dimensional gel electrophoresis identified 13 different proteins migrating at 60 kDa; 5 were splice variants of HSP60, and 2 corresponded with a protein associated with MYC (PAM). CONCLUSIONS: There is an increased prevalence of autoantibodies that bind to proteins migrating at 60 kDa in subjects with schizophrenia. Potential target antigens include HSP60 and PAM.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Use of the quality of well-being self-administered version (QWB-SA) in assessing health-related quality of life in depressed patients.

BACKGROUND: This study evaluated the cross-sectional and longitudinal relationship between depression severity and the Quality of Well-Being scale self-administered version (QWB-SA) in subjects diagnosed with current major depression. METHODS: The research design was prospective and observational. Data were collected on a convenience sample of 58 subjects. Additional measures included the Quality of Well-Being scale interviewer-version (interviewer-QWB), Hamilton Rating Scale for Depression (HRSD-17), Beck Depression Inventory, and each were collected at baseline, 4 weeks, and 4 months postmedication treatment. RESULTS: Cross-sectional and longitudinal QWB-SA scores were significantly correlated with depression severity and the interviewer-QWB. Treatment response, defined as 50% improvement in HRSD-17, was associated with 0.10 and 0.16 unit changes in the QWB-SA at 4 weeks and 4 months, respectively. The QWB-SA was significantly and negatively correlated with cross-sectional and longitudinal depression severity. LIMITATIONS: The study design was observational and used a convenience sample of subjects. CONCLUSIONS: The QWB-SA is less expensive to administer than the interviewer-QWB and is a useful alternative for determining the effectiveness and cost-effectiveness of treatments for depression relative to other physical and mental illness treatments.

Adult↗
PubMed2003

Efficacy of controlled-release paroxetine in the treatment of late-life depression.

BACKGROUND: Depression is the second most common neuropsychiatric disorder in older Americans, with significant clinical and public health costs. Despite advances in treatment, late-life depression remains a clinical challenge. Although the selective serotonin reuptake inhibitors (SSRIs) are the most common pharmacologic intervention for late-life depression, few placebo-controlled trials have assessed the efficacy of SSRIs for this condition. METHOD: In this 12-week, multicenter, placebo-controlled, flexible-dose, double-blind, randomized trial, 319 elderly patients (mean age = 70 years) were treated with controlled-release paroxetine (paroxetine CR) up to 50 mg/day (N = 104), immediate-release paroxetine (paroxetine IR) up to 40 mg/day (N = 106), or placebo (N = 109). Patients met DSM-IV criteria for major depressive disorder and had a total score of 18 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D). The primary efficacy measure was change from baseline to endpoint in HAM-D total score. RESULTS: The primary efficacy analysis showed an adjusted difference between change from baseline in HAM-D score for paroxetine CR and placebo of -2.6 (95% confidence interval [CI] = -4.47 to -0.73, p = .007) at the week 12 last-observation-carried-forward (LOCF) endpoint. The adjusted difference between paroxetine IR and placebo was -2.8 (95% CI = -4.65 to -0.99, p = .003) at week 12. Paroxetine CR and IR were more effective than placebo, with mean +/- SD endpoint HAM-D total scores of 10.0 +/- 7.41 and 10.0 +/- 7.10, respectively, for the active treatments compared with 12.6 +/- 7.34 for placebo. Response, defined as a score of 1 or 2 on the Clinical Global Impressions-global improvement scale, was achieved by 72% of paroxetine CR patients (LOCF; p < .002 vs. placebo), 65% of paroxetine IR patients (p = .06 vs. placebo), and 52% of placebo patients. Remission, defined as a HAM-D total score < or = 7, was achieved by 43% of paroxetine CR patients (LOCF; p = .009 vs. placebo), 44% of paroxetine IR patients (p = .01 vs. placebo), and 26% of placebo patients. In a post hoc analysis, mean HAM-D improvement for paroxetine CR and paroxetine IR was greater than for placebo in both chronically depressed patients (duration > 2 years) and those with short-term (< or = 2 years) depression. Dropout rates due to adverse events were 12.5% for paroxetine CR, 16.0% for paroxetine IR, and 8.3% for placebo. CONCLUSION: Paroxetine CR and paroxetine IR are effective and well tolerated treatments for major depressive disorder in elderly patients, including those with chronic depression.

Aged↗
PubMed2002

A descriptive analysis of minor depression.

OBJECTIVE: The authors provide a detailed clinical description of minor depression: its symptoms, level of disability, stability, and relationship to patient and family history of major depressive disorder. METHOD: Rigorous criteria for minor depression, including functional disability, were used to identify 226 individuals for a three-phase treatment study. This report presents data obtained on that study group during the first study phase, a 4-week placebo lead-in period. RESULTS: One hundred sixty-two subjects (72% of the initial study group) remained in the study for 4 weeks and continued to meet criteria for minor depression. Minor depression in these subjects was primarily characterized by mood and cognitive symptoms, not the classical neurovegetative signs and symptoms of depression. Approximately one-third of the subjects with minor depression had a past history of major depressive disorder, and nearly half had a family history of unipolar depressive disorder; however, neither factor affected the severity or quality of minor depressive symptoms. CONCLUSIONS: These data suggest that 1) minor depression is not evanescent; 2) minor depression is characterized by mood and cognitive symptoms rather than neurovegetative symptoms; 3) minor depression may occur either independently of a lifetime history of major depressive disorder or as a stage of illness in the course of recurrent unipolar depressive disorder; and 4) depressive disorders should be conceptualized as a continuum of severity.

Adolescent↗
PubMed2002

Long-term antidepressant treatment.

Major depressive disorder (MDD) is a common and costly illness. Recent research suggests that MDD is a lifelong condition for many patients. This has stimulated researchers to identify risk factors associated with an increased frequency of relapse and recurrence of major depression. One of the most important of these risk factors is an incomplete response to acute treatment. These data have led investigators to pursue techniques that enhance the acute response of patients to therapy, and study whether long-term treatment with antidepressants may prevent relapse and recurrence of MDD. Data from these trials suggest that continuation and maintenance treatment of MDD confers some protection against deteriorating back into an episode after acute treatment and against developing another episode of MDD.

Antidepressive Agents↗