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Biomedical subjects

David J Kupfer

Publications and source records attributed to David J Kupfer.

At least 19 recordsLinked to original sources
PubMed2005

Presenting characteristics of depressed outpatients as a function of recurrence: preliminary findings from the STAR*D clinical trial.

OBJECTIVES: Recurrent depression predicts risk for subsequent episodes, but it is unclear how it relates to demographic features, course of illness, and clinical presentation. METHODS: We report on the baseline data for the first 1500 patients enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org). Patients were required to have a DSM-IV diagnosis of nonpsychotic major depression and to score > or = 14 on the 17-item Hamilton rating scale for depression. Status with respect to recurrent depression and other aspects of illness course and demographic features were ascertained at intake, along with measures of depression and concurrent general medical illness. RESULTS: Patients with recurrent depression were older, had an earlier age of onset, and were more likely to have a positive family history of depression than first episode patients. However, recurrent patients were less likely to be chronic and reported shorter current episodes than first episode patients, something that was largely confined to females. Recurrent patients were more likely than first episode patients to report non-essential aspects of mood, cognition, and somatic symptoms, although largely as a consequence of greater overall depressive symptom severity. CONCLUSIONS: As compared to single episode depressions, recurrent depression was associated with greater symptom severity and illness characteristics suggestive of greater underlying risk, but not other demographic characteristics than age. Risk for recurrence appeared to be distinct from chronic depression. A subset of chronic first episode patients may lack the capacity to remit and may therefore be distinct from those with recurrent episodes.

Adolescent↗
PubMed2005

Structural brain changes in bipolar disorder using deformation field morphometry.

The objective of this study was to investigate anatomical brain abnormalities in adult bipolar patients using a deformation field morphometry technique. Our sample consisted of 32 right-handed bipolar I patients (men/women=16/16) and 32 right-handed, age and gender matched healthy controls. Deformation field morphometry analysis was performed on three-dimensional spoiled gradient recalled acquisition images. We found gender-specific structural differences between bipolar patients and healthy individuals. Bipolar men had significantly larger lateral ventricles (especially pronounced in the left hemisphere) and smaller left dorsolateral prefrontal cortex than healthy male controls. Our results are complementary to the findings of functional imaging and post-mortem studies that demonstrate abnormalities in the dorsolateral prefrontal cortex in bipolar patients.

Adolescent↗
PubMed2005

1H Magnetic resonance spectroscopy study of dorsolateral prefrontal cortex in unipolar mood disorder patients.

Neuroimaging and postmortem studies have suggested the involvement of the dorsolateral prefrontal cortex (DLPFC) in the pathophysioloy of unipolar disorder. We examined with in vivo 1H magnetic resonance spectroscopy (MRS) the levels of specific metabolites in the DLPFC of adult unipolar patients and the role of illness chronicity on DLPFC abnormalities. Nineteen unmedicated unipolar mood disorder patients and 19 age- and gender-matched healthy controls underwent a short echo-time 1H MRS examination localized to an 8-cm3 single voxel placed in the left DLPFC. There were no significant differences in metabolite levels, including N-acetylaspartate (NAA), phosphocreatine plus creatine (PCr+Cr) and choline-containing-compounds (GPC+PC), between the two groups. However, NAA/PCr+Cr ratios were significantly lower in the chronic than in the less chronically ill patients and healthy controls. The low levels of NAA/PCr+Cr ratios in the left DLPFC of unipolar patients who had been more chronically ill suggest a potential role for illness chronicity in neuronal abnormalities in the DLPFC in unipolar disorder. This could possibly be accounted for by neurodegenerative processes arising with the progression of the illness. Future 1H MRS investigations should longitudinally examine the role of illness chronicity on DLPFC abnormalities and their relationship with the symptoms of unipolar disorder.

Adult↗
PubMed2005

Alterations in regional cerebral glucose metabolism across waking and non-rapid eye movement sleep in depression.

BACKGROUND: Depression is associated with sleep disturbances, including alterations in non-rapid eye movement (NREM) sleep. Non-rapid eye movement sleep is associated with decreases in frontal, parietal, and temporal cortex metabolic activity compared with wakefulness. OBJECTIVE: To show that depressed patients would have less of a decrease than controls in frontal metabolism between waking and NREM sleep and to show that during NREM sleep, they would have increased activity in structures that promote arousal. DESIGN: Subjects completed electroencephalographic sleep and regional cerebral glucose metabolism assessments during both waking and NREM sleep using [(18)F]fluoro-2-deoxy-D-glucose positron emission tomography. SETTING: General clinical research center. PATIENTS: The study included 29 unmedicated patients who met the Structured Clinical Interview for DSM-IV criteria for current major depression and who had a score of 15 or greater on a 17-item Hamilton Rating Scale for Depression and 28 medically healthy subjects of comparable age and sex who were free of mental disorders. MAIN OUTCOME MEASURES: Electroencephalographic sleep and regional cerebral metabolism during waking and NREM sleep. RESULTS: Depressed patients showed smaller decreases than healthy subjects in relative metabolism in broad regions of the frontal, parietal, and temporal cortex from waking to NREM sleep. Depressed patients showed larger decreases than healthy subjects in relative metabolism in the left amygdala, anterior cingulate cortex, cerebellum, parahippocampal cortex, fusiform gyrus, and occipital cortex. However, in post hoc analyses, depressed patients showed hypermetabolism in these areas during both waking and NREM sleep. CONCLUSIONS: The smaller decrease in frontal metabolism from waking to NREM sleep in depressed patients is further evidence for a dynamic sleep-wake alteration in prefrontal cortex function in depression. Hypermetabolism in a ventral emotional neural system during waking in depressed patients persists into NREM sleep.

Adult↗
PubMed2005

Two-year outcomes for interpersonal and social rhythm therapy in individuals with bipolar I disorder.

CONTEXT: Numerous studies have pointed to the failure of prophylaxis with pharmacotherapy alone in the treatment of bipolar I disorder. Recent investigations have demonstrated benefits from the addition of psychoeducation or psychotherapy to pharmacotherapy in this population. OBJECTIVE: To compare 2 psychosocial interventions: interpersonal and social rhythm therapy (IPSRT) and an intensive clinical management (ICM) approach in the treatment of bipolar I disorder. DESIGN: Randomized controlled trial involving 4 treatment strategies: acute and maintenance IPSRT (IPSRT/IPSRT), acute and maintenance ICM (ICM/ICM), acute IPSRT followed by maintenance ICM (IPSRT/ICM), or acute ICM followed by maintenance IPSRT (ICM/IPSRT). The preventive maintenance phase lasted 2 years. SETTING: Research clinic in a university medical center. PARTICIPANTS: One hundred seventy-five acutely ill individuals with bipolar I disorder recruited from inpatient and outpatient settings, clinical referral, public presentations about bipolar disorder, and other public information activities. INTERVENTIONS: Interpersonal and social rhythm therapy, an adaptation of Klerman and Weissman's interpersonal psychotherapy to which a social rhythm regulation component has been added, and ICM. MAIN OUTCOME MEASURES: Time to stabilization in the acute phase and time to recurrence in the maintenance phase. RESULTS: We observed no difference between the treatment strategies in time to stabilization. After controlling for covariates of survival time, we found that participants assigned to IPSRT in the acute treatment phase survived longer without a new affective episode (P = .01), irrespective of maintenance treatment assignment. Participants in the IPSRT group had higher regularity of social rhythms at the end of acute treatment (P<.001). Ability to increase regularity of social rhythms during acute treatment was associated with reduced likelihood of recurrence during the maintenance phase (P = .05). CONCLUSION: Interpersonal and social rhythm therapy appears to add to the clinical armamentarium for the management of bipolar I disorder, particularly with respect to prophylaxis of new episodes.

Adult↗
PubMed2005

Cross-cultural validity of the structured clinical interview for panic-agoraphobic spectrum.

BACKGROUND: We sought to develop a series of assessment measures of psychiatric spectrum conditions associated with major DSM-IV mood and anxiety disorders that might capture the true phenotypes underlying these disorders. The specific objective of this report was to describe the methods we employed to create instruments that could cross linguistic and national boundaries and to evaluate the comparability of results obtained when one of these instruments, the Structured Clinical Interview for Panic-Agoraphobic Spectrum (SCI-PAS), was administered in the United States and in Italy. METHOD: After developing, in parallel, the English and the Italian versions of the SCI-PAS, identical protocols were conducted in patients and control samples at the University of Pittsburgh and the University of Pisa to examine the reliability and validity of the interview. RESULTS: Total and domain scores on the SCI-PAS were strikingly similar in the US and Italian patient groups and in controls. In addition, similarly high levels of inter-rater and test-retest reliability were found at the two sites. Finally, virtually identical patterns of relationships were found between the domains of the SCI-PAS and established measures of the same constructs. CONCLUSIONS: The SCI-PAS displays similar reliability and validity properties in the two versions. This suggests that the instrument taps a phenotype that is consistent in American and Italian patient and control populations.

Adult↗
PubMed2005

Circadian phase variation in bipolar I disorder.

Abnormalities in circadian rhythms are prominent features of bipolar I disorder (BD1). To investigate circadian variation in BD1, we evaluated morningness-eveningness (M/E), a stable trait reflecting circadian phase, using the composite scale (CS) among BD1 patients (DSM IV criteria; n = 75), unscreened controls (n = 349), and patients with schizophrenia (SZ) or schizoaffective disorder (SZA) (n = 81). Our analyses showed that CS scores correlated significantly with age but did not differ by gender among the controls. BD1 patients differed significantly from controls and from SZ/SZA patients when age was considered. CS scores were distributed bi-modally among BD1 cases. There are several possible reasons for the observed heterogeneity. Younger BD1 patients, and those with rapid mood swings, were significantly more likely to have lower CS scores (i.e., to score in the 'evening' range and to have later circadian phase). CS scores were also positively correlated with the age at onset and the duration of the most severe depressive episodes. These relationships were not observed among the SZ/SZA groups. Thus, distinct patterns of M/E were noted among BD1 patients and among BD1 subgroups. The impact of medication, mood state, and chronicity on CS scores needs to be considered.

Age Factors↗
PubMed2005

Achieving adequate outcomes in geriatric depression: standardized criteria for remission.

In the management of late-life depression, a major set of issues concerns the terms or language used to describe the course of illness and response to treatment. There appear to be considerable advantages in the application of standardized remission criteria. If one is primarily concerned with symptomatic remission and the resolution of a single or initial episode of depression, then a moderately strict criterion is sufficient, for example, Hamilton Rating Scale for Depression (HRSD) < or = 10. However, as the goal of treatment is to achieve complete recovery, which may reduce the risk for either relapse or recurrence, then there may be a strong advantage in applying a more stringent remission criterion such as HRSD < or = 6 or 7. The characteristics of the response pattern (ie, trajectory of clinical course) also can provide important prognostic information. Such pattern characteristics can be modeled with newer statistical methods, which in turn can better inform the course of future treatment. Finally, there is growing recognition that standardized remission criteria can be valuable for establishing treatment guidelines for late-life depression, as well as for educating clinicians and consumers.

Age Factors↗
PubMed2005

African-American participants in a bipolar disorder registry: clinical and treatment characteristics.

OBJECTIVES: The goal of this paper was to compare clinical characteristics and treatment history of African-American and Caucasian participants in a bipolar disorder registry. METHODS: The Western Pennsylvania Bipolar Disorder Registry used several recruitment methods to reach individuals self-identified as having bipolar disorder. Individuals who contacted and joined the registry completed an interviewer-administered questionnaire on clinical characteristics and treatment history. A sample of 2,718 registry participants was analyzed in order to compare these characteristics and history by race. RESULTS: African-Americans in the registry reported a greater number of inpatient hospitalizations (9.8 versus 4.4) than Caucasians, as well as a higher suicide attempt rate (64% versus 49%). African-American participants were more likely to report a family member with schizophrenia. With respect to psychotropic medication, African-Americans were less likely to report taking antimanic medication or benzodiazepines, but more likely to report taking antipsychotics than Caucasians. CONCLUSIONS: The present findings reinforce previous reports regarding the chronicity and severity of bipolar disorder among African-Americans. They also support previous studies that found high rates of attempted suicide among African-Americans with bipolar disorder. These findings provide further impetus for specific community and mental health services delivery efforts to reduce barriers to early accurate diagnosis and to appropriate ambulatory treatment for bipolar disorder.

Adolescent↗
PubMed2005

Recovery and functional outcomes following olanzapine treatment for bipolar I mania.

BACKGROUND: Typical experimental categorizations of treatment responses in bipolar disorder (BPD) patients may have limited relationship to clinical recovery or functional status, and there is inadequate research on such clinically important outcomes. METHODS: We analyzed data from a study of open continuation of olanzapine treatment following a 3-week placebo-controlled trial involving initially hospitalized adult subjects with DSM-IV BP-I mania to estimate rates and times to symptomatic remission (low scores on standardized symptomatic assessments) and clinical recovery (remission sustained>or=8 weeks), associated clinical factors, and functional outcomes. RESULTS: During treatment with olanzapine for 27.9+/-20.1 weeks, symptomatic remission was attained by 70% of subjects, half by 8 weeks (95% CI 6-10) weeks, and later lost by 82% of remitted subjects; remitted (versus non-remitted) subjects had slightly lower baseline clinical global impression scores and greater trial-completion. Sustained clinical recovery was attained by only 40 of 113 (35%) of subjects, half by 36 (95% CI 20-40) weeks, and later lost by 45%. Subjects with above-median (>12) initial Hamilton-Depression rating scale depression scores were half as likely to recover (p=0.016) and did so much later (36 versus 12 weeks) than those with lower scores. At final assessment, self-rated well being (SF-36 psychosocial functioning scores) improved substantially more among recovered versus non-recovered subjects (mean changes: 87% versus 23%), and two-thirds of recovered subjects remained unemployed-for-pay while half received disability-compensation. CONCLUSIONS: Clinically meaningful symptomatic remission and recovery in relatively severely ill adult bipolar I manic patients were achieved slowly and sustained by only some patients within an average of 7 months of continuous treatment. These clinically relevant outcomes were worse with relatively high initial dysphoria ratings. Well-being was rated higher by recovered subjects, but their ability to work and live independently were markedly impaired. These findings underscore the emerging view that BPD can often be severe, slow to remit, and disabling, particularly in association with prominent depression-dysphoria symptoms. Improved treatments for BPD are needed, guided by longitudinal assessments of clinically meaningful measures of symptomatic recovery and functional outcome.

Adult↗
PubMed2005

Functional impairment in the remission phase of bipolar disorder.

OBJECTIVES: The purpose of this study was to evaluate functional impairment in a group of patients with bipolar disorder in remission and to determine the extent of relationships between overall functioning and current depressive, manic and panic spectrum symptoms. METHOD: A subset of the patient population at the Pittsburgh site of the Systematic Treatment Enhancement Program in Bipolar Disorder (STEP-BD) study was evaluated in this study. The subsample comprises 103 male and female subjects with bipolar I disorder (n = 70), bipolar II disorder (n = 24), schizoaffective disorder - bipolar type (n = 4), or bipolar disorder NOS (n = 5). Subjects were evaluated in a period of remission (at least 4 weeks with no more than two depressive or manic symptoms). Subjects were assessed for overall functional status using the Work and Social Adjustment Scale (WSAS) and for current bipolar and panic spectrum symptoms using the Mood Spectrum Self-Report questionnaire (MOODS-SR) and Panic-Agoraphobic Spectrum Self-Report questionnaire (PAS-SR). RESULTS: The median WSAS total score in these remitted subjects was 14, indicating significant functional impairment. Regressing WSAS on current depressive, manic, and panic spectrum total scores, we observed a highly significant depressive spectrum effect (t = 4.9, df = 94, p < 0.0001), but non-significant panic and manic spectrum effects (t = 1.3, df = 94, p = 0.19 and t = -1.8, df = 94, p = 0.07, respectively). CONCLUSION: Bipolar disorder is associated with functional deficits even during periods of sustained and substantial remission. The degree of functional impairment is correlated with the degree of depressive spectrum symptoms.

Adult↗
PubMed2005

Metabolic syndrome in bipolar disorder: findings from the Bipolar Disorder Center for Pennsylvanians.

OBJECTIVE: This study sought to evaluate the presence of the metabolic syndrome in a group of 171 patients with bipolar disorder who were consecutively recruited in the Bipolar Disorder Center for Pennsylvanians. METHODS: Data were collected from participants entering the Bipolar Disorder Center for Pennsylvanians protocol between 2003 and 2004. The study focused on the presence of the metabolic syndrome, as defined by the National Cholesterol Education Program Expert Panel on Detection, Evaluation And Treatment of High Blood Cholesterol in Adults (NCEP ATP III). RESULTS: Thirty percent of the sample met the NCEP ATP III criterion for the metabolic syndrome, 49% met the criterion for abdominal obesity, 41% met the criterion for hypertriglyceridemia, 48% met the criterion for hypertriglyceridemia or were on a cholesterol-lowering medication, 23% met the criterion for low high-density lipoprotein cholesterol, 39% met the criterion for hypertension and 8% met the criterion for high fasting glucose or antidiabetic medication use. Patients with the metabolic syndrome and patients endorsing the obesity criterion were more likely (p = 0.05 and p = 0.004, respectively) to report a lifetime history of suicide attempt/s. CONCLUSIONS: The prevalence of the metabolic syndrome in patients with bipolar disorder is alarmingly high, as it is for the general population. The prevalence of obesity is even higher than the already very high prevalence that has been estimated for the US general population. Our findings are a reason for concern, considering the difficulty in implementing prevention and treatment programs in the bipolar population. We strongly support the development and testing of interventions specifically designed for preventing and treating the metabolic syndrome and its components in patients with bipolar disorder.

Academic Medical Centers↗
PubMed2005

Body pain and treatment response in late-life depression.

OBJECTIVE: The authors investigated the influence of body pain on 1) time to treatment response and 2) suicidal ideation, in late-life depression. They hypothesized that higher levels of body pain would predict a longer time to and lower likelihood of response, and increased levels of suicidal ideation. METHODS: Subjects (N=187) were older adult outpatients (age > or =69 years), with current episodes of major depression, who were openly treated with paroxetine up to 40 mg daily and weekly interpersonal psychotherapy. Response was defined as 3 consecutive weeks of Hamilton Rating Scale for Depression at < or =10. Body pain was measured with the Bodily Pain Index of the SF-36 quality-of-life assessment. Authors used survival-analysis models on the responder sample to test the effect of body pain on response, after controlling for severity of depression. RESULTS: Overall response rate was 75.4%. Nonresponders reported more severe pain at baseline. After covarying for severity of baseline depression, no effect was found for physical pain on time-to-response or degree of suicidality. Bodily pain remained stable during acute treatment for responders, independent of depression response to combination psychotherapy and antidepressant treatment. CONCLUSIONS: Older adult patients with higher levels of physical pain can still respond to antidepressant treatment; however, reported bodily pain may be associated with a more difficult-to-treat depression.

Activities of Daily Living↗
PubMed2005

A pilot study of standardized treatment in geriatric bipolar disorder.

OBJECTIVE: The authors sought to determine the feasibility of treating elderly adults with bipolar disorder under standardized-treatment conditions. METHODS: Thirty-one patients age 60 and older with bipolar disorder were treated in standardized pathways. Mood state was checked at each study visit with the Hamilton Rating Scale for Depression-17 item (Ham-D-17) and the Young Mania Rating Scale (YMRS). RESULTS: Defining "well days" as both Ham-D and YMRS scores of <or=10, the mean percentage of well days was 72.5 (range: 0%-100%) over study participation. CONCLUSIONS: Treating older adults with bipolar disorder under standardized treatment is feasible and is associated with low symptom levels. However, most older adults with bipolar disorder do not experience sustained recovery.

Adolescent↗
PubMed2005

Pain predicts longer time to remission during treatment of recurrent depression.

INTRODUCTION: Pain and depression are mutually exacerbating. We know that both of these syndromes predict the future occurrence of the other. It has not been shown, however, whether the presence of pain slows the effect of treatment for depression. We hypothesized that greater pain and somatic scores prior to treatment with imipramine and interpersonal psychotherapy would predict a slowed time to remission from depression. METHOD: We performed secondary data analyses of an archived study. Subjects (N = 230) were between 21 and 65 years of age and were enrolled in a study of maintenance treatment for recurrent unipolar depression. Patients had to meet Research Diagnostic Criteria (RDC) for a major depressive episode and historical requirements for at least 3 prior episodes and clear remissions (according to RDC). Patients were also required to have a minimum Hamilton Rating Scale for Depression score of 15 and a minimum score of 7 on the Raskin Severity of Depression Scale. This report describes the acute treatment phase, during which all subjects received combination therapy consisting of imipramine hydrochloride (150 to 300 mg) and interpersonal psychotherapy. Pain and somatization were measured with the Hopkins Symptom Checklist. RESULTS: Higher levels of both pain and somatization predicted a longer time to remission. After controlling for baseline severity of depression, only pain was still significant in predicting a longer time to remission. Headache and muscle soreness were the 2 variables from the pain index whose presence independently predicted a slower remission. Both pain and somatization improved during acute treatment. Subjects with more pain and somatization, after controlling for severity of depression, reported more suicidality. Women reported more pain than men. CONCLUSIONS: Pain, but not somatization, predicted a longer time to remission and may be a marker of a more difficult-to-treat depression. Adults with recurrent depression should be screened for the presence of pain prior to treatment, as the presence of these symptoms may require more aggressive treatment or may be a marker for suicidality or the use of dual-mechanism antidepressants.

Antidepressive Agents, Tricyclic↗
PubMed2005

The pharmacological management of depression.

Depressive disorders are common, recurrent, and chronic, and require treatment A review of the symptom picture and current drug targets demonstrates the need for accurate assessment of depression severity, including suicidality. The initial focus of treatment is rapid resolution of symptoms during an acute phase, followed by continuation. Maintenance treatment is indicated if the risk of recurrence is high. The range of available medications is considerable and the benefit/risk ratio is acceptable. Depression is diagnosable across the life span and treatable at every age (although recent disagreement has arisen with regard to young patients). Comorbidity, both psychiatric and medical, need to be assessed, as does the possible presence of two subtypes of depression (psychotic and bipolar) often requiring different interventions. It is expected that the next generation of antidepressants would be associated with more specific disease and outcome biomarkers.

Adolescent↗