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Biomedical subjects

Jerrold F Rosenbaum

Publications and source records attributed to Jerrold F Rosenbaum.

At least 37 records · Page 2Linked to original sources
PubMed2004

Obesity among outpatients with major depressive disorder.

Studies focusing on the prevalence of obesity in Major Depressive Disorder (MDD), or the impact of excess body fat on the treatment of MDD are lacking. The aim of the present work is to systematically study obesity in MDD outpatients. A total of 369 MDD outpatients enrolled in an 8-wk trial of 20 mg fluoxetine had height and weight measured at baseline. We then examined: (1) the prevalence of being overweight or obese, (2) the relationship between obesity and a number of demographic and clinical variables, and, (3) the relationship between relative body weight and obesity with clinical response. We found that more than 50% of patients were overweight [body mass index (BMI) > or =2 5 kg/m2], while 20% were obese (BMI > or = 30 kg/m2). Obese patients presented with worse somatic well-being scores than non-obese MDD patients, but they did not differ with respect to depression severity, anxiety, somatic complaints, hopelessness or hostility. Greater relative body weight, but not obesity, predicted non-response. In conclusion, greater relative body weight was found to place MDD outpatients at risk for fluoxetine resistance.

Adult↗
PubMed2004

Moderating effects of major depression on patterns of comorbidity in patients with panic disorder.

Given the high rate of co-occurring major depression in patients with panic disorder, it is unclear whether patterns of comorbidity in individuals with panic disorder reported in the literature are associated with panic disorder or with the presence of major depression. Subjects were 231 adult subjects with panic disorder and major depression (n=102), panic disorder without comorbid major depression (n=29), major depression without comorbid panic disorder (n=39), and neither panic disorder nor major depression (n=61). Subjects were comprehensively assessed with structured diagnostic interviews that examined psychopathology across the life cycle. Panic disorder, independently of comorbidity with major depression, was significantly associated with comorbid separation anxiety disorder, simple phobia, obsessive-compulsive disorder, generalized anxiety disorder, and agoraphobia. Major depression, independently of comorbidity with panic disorder, was significantly associated with comorbidity with psychoactive substance use disorders and childhood disruptive behavior disorders. Overanxious disorder was associated with both panic disorder and major depression. Major depression has important moderating effects on patterns of comorbidity of panic disorder in referred adults.

Adult↗
PubMed2004

A preliminary open study of the tolerability and effectiveness of nefazodone in major depressive disorder: comparing patients who recently discontinued an SSRI with those on no recent antidepressant treatment.

Anecdotal evidence suggests that the recent discontinuation of an SSRI may confound the tolerability of the initiation of nefazodone treatment. We sought to determine whether recent discontinuation of an SSRI interferes with effectiveness and/or tolerability of nefazodone. Twenty-six depressed subjects, 21-63 years old, were recruited at the Massachusetts General Hospital. Thirteen subjects (50%) had discontinued an SSRI within 1-4 weeks due to ineffectiveness and/or side effects. Thirteen subjects (50%) had not taken antidepressants for the previous 6 months. Subjects were administered open nefazodone 50 mg p.o. b.i.d., and doses were increased as tolerated to a maximum of 600 mg/day. Subjects were followed for 12 weeks and were assessed for response and side effects using HAM-D-6 and clinical interviews. Both groups improved significantly on nefazodone; however, there was no statistically significant difference in response (>or=50% decrease in HAM-D-6) rates between completers with prior SSRI treatment (80%) and completers without recent exposure to antidepressants (67%). Response rates based on intent-to-treat (ITT) analysis were 31% for both groups. Association between prior SSRI treatment and discontinuation of nefazodone due to side effects or non-response was not statistically significant. Our study suggests that the rate of negative outcomes with nefazodone is no different whether patients have recently failed an SSRI.

Adult↗
PubMed2004

Pregnancy complications associated with childhood anxiety disorders.

To determine whether perinatal complications predict childhood anxiety disorders independently of parental psychopathology, we systematically assessed pregnancy and delivery complications and psychopathology in a sample of children (mean age=6.8 years) at high risk for anxiety disorders whose parents had panic disorder with (n=138) or without (n=26) major depression, and in contrast groups of offspring of parents with major depression alone (n=47), or no mood or anxiety disorders (n=95; total N=306). Psychopathology in the children was assessed by structured diagnostic interviews (K-SADS), and pregnancy and delivery complications were assessed using the developmental history module of the DICA-P. Number of pregnancy complications predicted multiple childhood anxiety disorders independently of parental diagnosis (odds ratio=1.6 [1.4-2.0]). This effect was accounted for by heavy bleeding requiring bed-rest, hypertension, illness requiring medical attention, and serious family problems. Associations remained significant when lifetime child mood and disruptive behavior disorders were covaried. Results suggest that prenatal stressors may increase a child's risk for anxiety disorders beyond the risk conferred by parental psychopathology alone.

Anxiety Disorders↗
PubMed2004

The prevalence and clinical correlates of anger attacks during depressive episodes in bipolar disorder.

BACKGROUND: Anger attacks, characterized by sudden episodes of intense anger with autonomic arousal, have been described in patients with major depressive disorder (MDD). This study compared the prevalence and clinical significance of anger attacks in unipolar versus bipolar depression. METHODS: Using the questionnaire of Fava et al. [Psychopharmacol. Bull. 27(3) (1991) 275-279], we assessed rates of anger attacks among outpatients with MDD (n=50) or bipolar disorder (BPD) (n=29) who were currently in a pure depressive episode. RESULTS: Anger attacks were significantly more common among bipolar (62%) than unipolar (26%) depressed individuals. In a multiple logistic regression, the presence of anger attacks emerged as a significant predictor of bipolarity. LIMITATIONS: This preliminary finding should be confirmed in a larger sample. CONCLUSIONS: These results suggest that anger attacks may be a common feature of bipolar depression.

Adult↗
PubMed2004

Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design.

STAR*D is a multisite, prospective, randomized, multistep clinical trial of outpatients with nonpsychotic major depressive disorder. The study compares various treatment options for those who do not attain a satisfactory response with citalopram, a selective serotonin reuptake inhibitor antidepressant. The study enrolls 4000 adults (ages 18-75) from both primary and specialty care practices who have not had either a prior inadequate response or clear-cut intolerance to a robust trial of protocol treatments during the current major depressive episode. After receiving citalopram (level 1), participants without sufficient symptomatic benefit are eligible for randomization to level 2 treatments, which entail four switch options (sertraline, bupropion, venlafaxine, cognitive therapy) and three citalopram augment options (bupropion, buspirone, cognitive therapy). Those who receive cognitive therapy (switch or augment options) at level 2 without sufficient improvement are eligible for randomization to one of two level 2A switch options (venlafaxine or bupropion). Level 2 and 2A participants are eligible for random assignment to two switch options (mirtazapine or nortriptyline) and to two augment options (lithium or thyroid hormone) added to the primary antidepressant (citalopram, bupropion, sertraline, or venlafaxine) (level 3). Those without sufficient improvement at level 3 are eligible for level 4 random assignment to one of two switch options (tranylcypromine or the combination of mirtazapine and venlafaxine). The primary outcome is the clinician-rated, 17-item Hamilton Rating Scale for Depression, administered at entry and exit from each treatment level through telephone interviews by assessors masked to treatment assignments. Secondary outcomes include self-reported depressive symptoms, physical and mental function, side-effect burden, client satisfaction, and health care utilization and cost. Participants with an adequate symptomatic response may enter the 12-month naturalistic follow-up phase with brief monthly and more complete quarterly assessments.

Adolescent↗
PubMed2004

Lack of association between behavioral inhibition and psychosocial adversity factors in children at risk for anxiety disorders.

OBJECTIVE: In a previous controlled study of offspring at risk for anxiety disorders, the authors found that parental panic disorder with comorbid major depression was associated with child behavioral inhibition, the temperamental tendency to be quiet and restrained in unfamiliar situations. To explore whether this association was mediated by environmental factors, the authors examined associations between psychosocial adversity variables and behavioral inhibition in this group of children. METHOD: Subjects included 200 offspring of parents with panic disorder and/or major depression and 84 comparison children of parents without mood or anxiety disorders. Behavioral inhibition was assessed through laboratory observations. The associations between behavioral inhibition and the following psychosocial factors were examined: socioeconomic status; an index of adversity factors found in previous studies to be additively associated with child psychopathology; family intactness, conflict, expressiveness, and cohesiveness; exposure to parental psychopathology; sibship size; birth order; and gender. RESULTS: The results showed no associations between behavioral inhibition and any of the psychosocial factors in the study group as a whole, despite adequate power to detect medium effect sizes. Among low-risk comparison children only, some definitions of behavioral inhibition were associated with low socioeconomic status, low family cohesion, and female gender. CONCLUSIONS: The results suggest that the psychosocial adversity factors examined in this study do not explain the previous finding that offspring of parents with panic disorder are at high risk for behavioral inhibition.

Anxiety Disorders↗
PubMed2004

Ziprasidone augmentation of selective serotonin reuptake inhibitors (SSRIs) for SSRI-resistant major depressive disorder.

BACKGROUND: Due to their favorable side-effect profile, atypical antipsychotic agents offer important therapeutic advantages in mood disorders. Ziprasidone, an atypical antipsychotic agent with strong 5-HT(1A) agonist activity, may be particularly useful when used in conjunction with standard antidepressants in treatment-resistant depression. The purpose of this study is to test this hypothesis in depressed outpatients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor (SSRI). METHOD: Twenty patients with major depressive disorder (MDD) who had failed to experience a clinical response to an adequate trial of an SSRI were treated with open-label ziprasidone in addition to their SSRI for 6 weeks between February 2002 and December 2002. MDD was diagnosed with the Structured Clinical Interview for DSM-IV Axis I disorders. Clinical response was defined as a 50% or greater decrease in depressive symptoms during the course of the trial (baseline to endpoint), as measured by the HAM-D-17 total score. RESULTS: Thirteen of 20 patients (65.0%) completed the trial. Using a completer analysis, 8 patients (61.5%) were classified as responders. An intent-to-treat (ITT) analysis resulted in 10 responders (50.0%). The overall proportion of remitters was 5 of 13 (38.5%) using a completer analysis and 5 of 20 (25.0%) using the ITT analysis. Ziprasidone administration appeared to be safe, with no clinically significant QTc prolongation or severe adverse events observed in any of the study participants. CONCLUSION: These results suggest a possible augmentation role for ziprasidone when used in conjunction with SSRIs in SSRI-resistant MDD.

Adult↗
PubMed2004

Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 1: predictors of clinical response in fluoxetine-resistant depression.

OBJECTIVE: In the present study, we assessed the relationship between serum folate, vitamin B12, and homocysteine levels and clinical response in patients with major depressive disorder (MDD) who had previously failed to respond to open treatment with fluoxetine 20 mg/day and were enrolled in a 4-week, double-blind trial of either (1) fluoxetine dose increase, (2) lithium augmentation of fluoxetine, or (3) desipramine augmentation of fluoxetine. METHOD: Fifty-five outpatients (mean +/- SD age = 41.7 +/- 10.6 years; 50.9% women) with MDD as assessed with the Structured Clinical Interview for DSM-III-R who were enrolled in the double-blind trial had serum folate, vitamin B12, and homocysteine measurements completed at baseline (prior to fluoxetine treatment initiation). Folate levels were classified as either low (< or = 2.5 ng/mL) or normal. Vitamin B12 levels were classified as either low (< or = 200 pg/mL) or normal. Homocysteine levels were classified as either elevated (> or = 13.2 micromol/L) or normal. With the use of a logistic regression, we then assessed the relationship between (1) low or normal folate levels, (2) normal or low B12 levels, and (3) elevated or normal homocysteine levels and clinical response to double-blind treatment. The study was conducted from November 1992 to January 1999. RESULTS: Low serum folate levels (chi2=3.626, p =.04), but not elevated homocysteine (p >.05) or low vitamin B12 levels (p >.05), were associated with poorer response to treatment. The response rates for patients with (N = 14) and without (N = 38) low folate levels were 7.1% versus 44.7%, respectively. CONCLUSION: Low serum folate levels were found to be associated with further treatment resistance among patients with fluoxetine-resistant MDD.

Adult↗
PubMed2004

Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 2: predictors of relapse during the continuation phase of pharmacotherapy.

OBJECTIVE: In the present study, we assessed the relationship between serum folate, vitamin B12, and homocysteine levels on the rate of relapse in outpatients with remitted major depressive disorder (MDD) during a 28-week continuation phase of treatment with fluoxetine. METHOD: Seventy-one outpatients (mean +/- SD age = 40.2 +/- 11.1 years; 56.3% women) with MDD (as assessed with the Structured Clinical Interview for DSM-III-R) who had remitted and who were enrolled in the continuation phase of treatment with fluoxetine had serum folate, vitamin B12, and homocysteine measurements completed at baseline (prior to acute-phase treatment). Patients were followed for 28 weeks of continued treatment with fluoxetine 40 mg/day to monitor for depressive relapse. Folate levels were classified as either low (< or = 2.5 ng/mL) or normal. Vitamin B12 levels were classified as either low (< or = 200 pg/mL) or normal. Homocysteine levels were classified as either elevated (> or = 13.2 micromol/L) or normal. With the use of separate logistic regressions, we then assessed the relationship between folate, vitamin B12, and homocysteine level status and relapse. The study was conducted from November 1992 to January 1999. RESULTS: The presence of low serum folate levels (p =.004), but not low B12 (p >.05) or elevated homocysteine levels (p >.05), was associated with relapse during continuation treatment with fluoxetine. The relapse rates for patients with (N = 7) and without (N = 64) low folate levels were 42.9% versus 3.2%, respectively. CONCLUSION: Low serum folate levels were found to place patients with remitted MDD at risk for depressive relapse during the continuation phase of treatment with fluoxetine.

Adult↗
PubMed2004

The development of clonazepam as a psychotropic: the massachusetts general hospital experience.

The pathophysiology of anxiety disorders is not clearly understood; therefore, clinical observation, case reports, and case reviews continue to enhance physicians' understanding of disease and treatment mechanisms. At Massachusetts General Hospital (MGH), physicians and researchers are guided by the recognition that available approved treatments are a small subset of what is sensible to try in anxiety disorders and have thus chosen to remain open minded and prepared to challenge assumptions about therapeutic agents and to explore new uses, including early work with high-potency benzodiazepines. Clinical trials established alprazolam as efficacious for panic disorder, and the agent was widely prescribed for patients at MGH after its approval. Soon, however, clinical observation suggested a short duration of benefit for a given dose in some patients. In some cases, patients who missed a dose reported rebound worsening. In response to the apparent problematic pharmacokinetics of alprazolam, members of the MGH psychiatry department pursued investigation that ultimately established the antipanic efficacy of clonazepam as well as examined its effectiveness in the treatment of other disorders, such as bipolar disorder and social phobia. The process of exploring new uses of older agents remains a worthy effort while we await newer agents with innovative mechanisms of action.

Anxiety Disorders↗
PubMed2003

Association of a genetic marker at the corticotropin-releasing hormone locus with behavioral inhibition.

BACKGROUND: Behavioral inhibition to the unfamiliar (BI), a heritable temperamental profile involving an avoidant response to novel situations, may be an intermediate phenotype in the development of anxiety disorders. Corticotropin-releasing hormone (CRH) is a key mediator of the stress response through its effects on the hypothalamic-pituitary-adrenal axis and limbic brain systems. Transgenic mice overexpressing CRH exhibit BI-like behaviors, implicating this gene in the development of the phenotype. METHODS: We genotyped a marker tightly linked to the CRH locus in 85 families of children who underwent laboratory-based behavioral assessments of BI and performed family-based association analyses. RESULTS: We observed an association between an allele of the CRH-linked locus and BI (p =.015). Among offspring of parents with panic disorder, this association was particularly marked (p =.0009). We further demonstrate linkage disequilibrium between this marker and single nucleotide polymorphisms encompassing the CRH gene. CONCLUSIONS: These results are consistent with the possibility that variants in the CRH gene are associated with anxiety proneness.

Anxiety Disorders↗
PubMed2003

Serotonin transporter polymorphisms and adverse effects with fluoxetine treatment.

BACKGROUND: The short (S) allele of the serotonin transporter gene-linked polymorphic region (5HTTLPR) has been associated with poorer antidepressant response in major depressive disorder (MDD) and with antidepressant-induced mania. This study investigated a possible association with treatment-emergent insomnia or agitation. METHODS: Thirty-six outpatients with MDD were genotyped at 5HTTLPR and treated with open-label fluoxetine up to 60 mg/day. Treatment-emergent adverse effects were assessed at each study visit. RESULTS: Of nine subjects homozygous for the "S" allele, seven (78%) developed new or worsening insomnia, versus 6 of 27 (22%) non-"S"-homozygous subjects (Fisher's exact p =.005). Similarly, six of nine subjects homozygous for the "S" allele (67%) developed agitation, versus 2 of 27 (7%) of non-"S"-homozygous subjects (Fisher's exact p =.001). CONCLUSIONS: The "S" allele of the 5HTTLPR may identify patients at risk for developing insomnia or agitation with fluoxetine treatment. This preliminary result requires confirmation in larger samples.

Adult↗
PubMed2003

Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD).

The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was conceived in response to a National Institute of Mental Health initiative seeking a public health intervention model that could generate externally valid answers to treatment effectiveness questions related to bipolar disorder. STEP-BD, like all effectiveness research, faces many design challenges, including how to do the following: recruit a representative sample of patients for studies of readily available treatments; implement a common intervention strategy across diverse settings; determine outcomes for patients in multiple phases of illness; make provisions for testing as yet undetermined new treatments; integrate adjunctive psychosocial interventions; and avoid biases due to subject drop-out and last-observation-carried-forward data analyses. To meet these challenges, STEP-BD uses a hybrid design to collect longitudinal data as patients make transitions between naturalistic studies and randomized clinical trials. Bipolar patients of every subtype with age >/= 15 years are accessioned into a study registry. All patients receive a systematic assessment battery at entry and are treated by a psychiatrist (trained to deliver care and measure outcomes in patients with bipolar disorder) using a series of model practice procedures consistent with expert recommendations. At every follow-up visit, the treating psychiatrist completes a standardized assessment and assigns an operationalized clinical status based on DSM-IV criteria. Patients have independent evaluations at regular intervals throughout the study and remain under the care of the same treating psychiatrist while making transitions between randomized care studies and the standard care treatment pathways. This article reviews the methodology used for the selection and certification of the clinical treatment centers, training study personnel, the general approach to clinical management, and the sequential treatment strategies offered in the STEP-BD standard and randomized care pathways for bipolar depression and relapse prevention.

Bipolar Disorder↗
PubMed2003

Behavioral inhibition and disinhibition as hypothesized precursors to psychopathology: implications for pediatric bipolar disorder.

Attention has been devoted over the past two decades to the identification of temperamental risk factors for child psychopathology. These qualities, evident in toddlerhood or earlier, have the advantage of being measurable in standardized laboratory observations well before children reach the age of onset or diagnosis of psychiatric disorders. Our group's programmatic research over the past 15 years, and that of others, has provided evidence linking "behavioral inhibition to the unfamiliar" in toddlerhood or early childhood with later social anxiety disorder. In addition, recent results by our group have suggested that "behavioral disinhibition" in early childhood, measured by the same laboratory methods, may be linked with later disruptive behavior and comorbid mood disorders. In this article, we discuss our approach to the study of temperamental precursors to disorders in high-risk children, summarize the literature linking behavioral inhibition and disinhibition to later psychopathology, and suggest directions to take in applying this methodology to the search for temperamental precursors to pediatric bipolar disorder.

Adolescent↗
PubMed2003

Serum cholesterol and serotonergic function in major depressive disorder.

Studies have revealed a relationship between serum cholesterol levels and serotonergic (5HT) function in healthy young adults. Patients with major depressive disorder (MDD) may have significant differences in cholesterol levels compared with healthy adults, while MDD patients with elevated cholesterol have a poorer prognosis for treatment response. The goal of the present study is to examine (1) the relationship between serum cholesterol levels and central 5HT function by way of the cortisol and prolactin response to the 5HT-selective agonist DL-fenfluramine in MDD patients and (2) differences in 5HT-function between MDD patients who present with and without elevated cholesterol. Fasting serum cholesterol levels were measured in 21 outpatients with MDD. After oral administration of 60 mg of DL-fenfluramine in these patients, cortisol and prolactin responses were measured to test whether cholesterol levels predicted the degree of cortisol or prolactin response. Cortisol and prolactin responses were compared between patients with and without elevated cholesterol levels, defined as >/=200 mg/dl. MDD patients with elevated cholesterol levels were more likely to demonstrate an attenuated cortisol response. There was no relationship between cholesterol levels and cortisol or prolactin response. Excess cholesterol may adversely affect the function of membrane-bound serotonergic structures, and this may explain why MDD patients with elevated cholesterol are more likely to exhibit attenuated neuroendocrine responses, less likely to respond to treatment and more likely to relapse.

Adult↗
PubMed2003

Axis III disorders in treatment-resistant major depressive disorder.

A number of naturalistic studies have found that medical co-morbidity conveys a worse long-term prognosis in the treatment of major depressive disorder (MDD). The purpose of this study was to test whether the presence of co-morbid medical conditions can predict clinical response in patients with treatment-resistant MDD (TRD) treated with open-label nortriptyline (NT). Ninety-two patients with TRD entered a 6-week open trial of NT. The presence of co-morbid medical disorders was assessed during the screen visit. The degree of medical co-morbidity during the screen visit was then quantified with the use of the Cumulative Illness Rating Scale-Geriatric Version (CIRS(G)). We tested whether CIRS(G) scores predicted clinical response or depression severity at endpoint. CIRS scores at baseline did not significantly predict treatment response. The results of this study fail to confirm the relationship between co-morbid medical conditions and poor outcome in the treatment of MDD for patients with TRD. Patients with TRD and co-morbid medical conditions can be expected to respond to antidepressants as well as their counterparts without concurrent axis III co-morbidity. The CIRS(G) scores for this TRD sample were lower than those reported for geriatric depression, or for depressed patients with severe medical illness, common in medical and surgical wards and in most specialty clinics of large academic centers. Thus, the present results cannot be generalized to such populations.

Adult↗