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D J Kupfer

Publications and source records attributed to D J Kupfer.

At least 91 records · Page 5Linked to original sources
PubMed1999

Accelerating antidepressant response in geriatric depression: a post hoc comparison of combined sleep deprivation and paroxetine versus monotherapy with paroxetine, nortriptyline, or placebo.

Speed of response is an important clinical issue in the treatment of depressed elderly patients. Our objective was to compare rapid response rates in a study combining therapeutic sleep deprivation (TSD) with paroxetine with two earlier randomized, double-blind studies in late-life depression, one of paroxetine versus nortriptyline and another of nortriptyline versus placebo. We measured depressive symptoms with the 17-item Hamilton Rating Scale of Depression (HRSD), defining rapid response as an HRSD < or = 10 by 2 weeks. With combination therapy (TSD + paroxetine), 9 of 13 patients (69%) experienced a rapid response. In the nortriptyline versus paroxetine study, nortriptyline brought about rapid response in 12 of 37 (32%) and paroxetine in 11 of 43 patients (26%). In the third study, rapid response to nortriptyline occurred in 10 of 41 patients (24%) and to placebo in 6 of 39 patients (15%). The overall chi square, including the rate of rapid response to placebo, was 14.87 (P = .005). The chi square on the four active treatment groups, excluding placebo, was 10.28 (P = .016). This preliminary observation suggests that combined therapy with TSD plus paroxetine may be twice as successful at achieving rapid response in elderly depressed patients than conventional monotherapy with medication or placebo. A prospective, placebo-controlled evaluation of this dual therapy is warranted.

Aged↗
PubMed1999

Consensus criteria for traumatic grief. A preliminary empirical test.

BACKGROUND: Studies suggest that symptoms of traumatic grief constitute a distinct syndrome worthy of diagnosis. AIMS: A consensus conference aimed to develop and test a criteria set for traumatic grief. METHOD: The expert panel proposed consensus criteria for traumatic grief. Receiver operator characteristic (ROC) analyses tested the performance of the proposed criteria on 306 widowed respondents at seven months post loss. RESULTS: ROC analyses indicated that three of four separation distress symptoms (e.g. yearning, searching, loneliness) had to be endorsed as at least 'sometimes true' and four of the final eight traumatic distress symptoms (e.g. numbness, disbelief, distrust, anger, sense of futility about the future) had to be endorsed as at least 'mostly true' to yield a sensitivity of 0.93 and a specificity of 0.93 for a diagnosis of traumatic grief. CONCLUSIONS: Preliminary analyses suggest the consensus criteria for traumatic grief have satisfactory operating characteristics, and point to directions for further refinement of the criteria set.

Grief↗
PubMed1999

Are age differences in sleep due to phase differences in the output of the circadian timing system?

Our aim was to evaluate whether age-related changes in the phase of the output of the circadian timing system (CTS) can explain age differences in habitual bedtime/wake time and in sleep consolidation parameters. Analyses focused on a group of healthy elderly people (older than 70 years) with no sleep problems and with similar subjective sleep quality as a young control group. The 2-week sleep diary data and 24h laboratory temperature recordings were examined for 70 subjects (22 young men [YM], 19 old men [OM], 29 old women [OW]). Polysomnographic (PSG) sleep data recorded during temperature data acquisition were also available for 62 subjects. These analyses made use of our recently developed technique to demask temperature rhythm data. As expected, compared to the young subjects, older subjects showed earlier habitual bedtime and wake time, more disturbed sleep, and a tendency for an earlier minimum of the circadian temperature rhythm. Despite sleep consolidation differences, the groups showed very similar habitual phase-angle differences (interval between the time occurrence of the fitted temperature minimum and habitual wake time). Both elderly and young subjects woke up on average 3 h after the temperature minimum. After controlling for the effects of age group, habitual bedtime and wake time were related to clock time phase of the circadian temperature rhythm, with an earlier phase associated with earlier habitual bedtime and wake time. None of the sleep consolidation parameters were linked to the temperature phase angle. In conclusion, sleep consolidation changes associated with healthy aging do not appear to be related to changes in the phase-angle difference between the output signal from the CTS and sleep.

Adult↗
PubMed1999

Paroxetine in the treatment of primary insomnia: preliminary clinical and electroencephalogram sleep data.

BACKGROUND: Primary insomnia is a persistent and recurrent disorder as well as a risk factor for depression. The goal of this study was to determine whether paroxetine, a nonsedating antidepressant, would be effective in the treatment of patients with primary insomnia. METHOD: Fifteen patients meeting DSM-IV criteria for primary insomnia received paroxetine at bedtime for 6 weeks in an open, flexible-dose trial (median dose = 20 mg). Patients were assessed with daily sleep diaries, baseline and treatment polysomnography, and weekly standardized clinical evaluations. RESULTS: Of the 14 patients who completed the study (1 dropped out owing to side effects), 11 improved with treatment, and 7 of these 11 no longer met diagnostic criteria for insomnia. Although self-reported sleep quality (measured by the Pittsburgh Sleep Quality Index) and daytime well-being (measured by the Profile of Mood States) improved with treatment, the quantity of sleep, measured by diary and by polysomnography, did not change consistently with these improvements. Power spectral analysis suggested that paroxetine treatment may be associated with decreases in power in frequencies within the delta and alpha frequency ranges. CONCLUSION: These results support the effectiveness of paroxetine in the acute treatment of primary insomnia. Further evaluation with controlled and longitudinal designs is warranted.

Adult↗
PubMed1999

Which elderly depressed patients remain well on maintenance interpersonal psychotherapy alone?: report from the Pittsburgh study of maintenance therapies in late-life depression.

The aim of this study was to identify elderly depressed patients who can remain well on maintenance Interpersonal Psychotherapy (IPT) alone, after discontinuation of antidepressant medication. Using Cox proportional hazards models, increased severity of depression at pretreatment was associated with increased recurrence rates, to an extent greater in patients maintained on monthly IPT than in those maintained on nortriptyline. The long-term response to maintenance IPT was correctly identified in 20/25 cases by a pretreatment Hamilton score of > or = 20. Fourteen of sixteen patients with pretreatment scores of > or = 20 experienced recurrence of major depression on maintenance IPT, while 6/9 patients with pretreatment scores of less than 20 did not. (Fisher exact P = .01). The same pattern of recurrence in relation to severity was not evident in maintenance placebo, nortriptyline, or combination treatment. In addition, Hamilton scores during continuation treatment were lower (< or = 7) among those who remained well on maintenance IPT than among those who had recurrences. Elderly patients whose depressions are milder at baseline and who show excellent symptomatic remission during acute and continuation therapy may be good candidates for monthly maintenance IPT after initial successful treatment with antidepressant medication and psychotherapy.

Age Factors↗
PubMed1999

A double-blind, placebo-controlled assessment of nortriptyline's side-effects during 3-year maintenance treatment in elderly patients with recurrent major depression.

The authors assessed the severity of nortriptyline's side-effects in older patients with recurrent major depression during placebo-controlled, double-blind maintenance therapy. Data were from 37 patients completing 2-3 years of maintenance therapy; 29 were on nortriptyline and eight were on placebo. The authors detected a time-by-treatment interaction for dry mouth (greater in nortriptyline-treated patients), but no increased association of nortriptyline with constipation, weight change or orthostatic symptoms. Heart rate was consistently higher in nortriptyline-maintained patients as compared with placebo. The total 'side-effect' score on the Asberg Rating Scale, as well as complaints of physical tiredness, daytime sleepiness and nocturnal sleep disturbance, were related primarily to residual depression rather than treatment with nortriptyline.

Aged↗
PubMed1999

EEG sleep measures in later-life bereavement depression. A randomized, double-blind, placebo-controlled evaluation of nortriptyline.

The authors examined 1) effects of nortriptyline (NT) on electroencephalographic (EEG) sleep measures in elderly patients with bereavement-related depression in remission under randomized, double-blind, placebo-controlled conditions, and 2) the effects of clinical remission on sleep after discontinuation of medication. Subjects were classified as responders to placebo (n = 9) or NT (n = 18) and had EEG sleep studies at three time-points: before treatment (T1), remitted on medication or placebo (T2), and remitted off medication or placebo (T3). As compared with placebo, NT was differentially associated with decreases in REM sleep time and percent and increases in REM sleep density (T2). No changes in EEG sleep measures occurred in placebo responders. REM sleep measures in NT responders reverted to T1 levels after T3, with persistence of robust clinical remission and normal subjective sleep quality. These data suggest that NT alters REM sleep, but that EEG sleep characteristics in bereavement-related depression persist into remission.

Aged↗
PubMed1999

Treatment of 70(+)-year-olds with recurrent major depression. Excellent short-term but brittle long-term response.

The authors compared response rates, by age (60-69 vs. 70+), to acute, continuation, and 1-year maintenance depression treatment. Patients (N = 180) received open combined treatment with nortriptyline (NT)/placebo and interpersonal psychotherapy (IPT). Patients who recovered then entered randomized, double-blind maintenance treatment with NT or placebo or received maintenance monthly IPT (combined with NT or placebo). Comparison of time-to-remission and recovery and absolute rates of remission, relapse, recovery, and recurrence yielded similar times to/rates of remission and recovery; however, older patients had far more recurrence during the first year of maintenance therapy. Although responses to acute and continuation treatment with combined NT and psychotherapy were similar, the older group had more recurrence in the first year of maintenance. Continuation of combined medication and psychotherapy may represent the best long-term treatment.

Age Factors↗
PubMed1999

Age at onset in geriatric bipolar disorder. Effects on clinical presentation and treatment outcomes in an inpatient sample.

The authors report on 62 inpatients over age 60 who met DSM-III-R criteria for bipolar disorder, divided into early- and late-onset groups by their median age at lifetime onset, 49 years, in order to examine differences in demographic and clinical characteristics, treatment parameters, and outcome in the two groups during a short-term hospitalization. The late-onset group was more likely to have psychotic features and to demonstrate cerebrovascular risk/burden. However, both groups had similar and highly significant improvements in the Brief Psychiatric Rating Scale, Global Assessment Scale, and the Mini-Mental State Exam, and 87% were able to be discharged to settings no more restrictive than those at admission.

Age of Onset↗
PubMed1998

Linkage and association analysis of chromosomal regions containing genes related to neuroendocrine or serotonin function in families with early-onset, recurrent major depression.

Recurrent unipolar depression with an early age of onset is a severe form of unipolar depression that has both genetic and environmental components. We genotyped the members of 16 families identified by probands with early onset (< or = 25 years), recurrent unipolar, major depression for 38 simple sequence tandem repeat polymorphisms (SSTRPs) from chromosomal regions containing 12 genes involved in neuroendocrine or serotonergic functioning. Pairwise linkage analysis was performed with the software package FASTLINK. The affected phenotype was defined four ways, and both dominant and recessive models of depression were analyzed. Seven SSTRPs showed lod scores > 1.00 at theta values between 0.10-0.20. The members of an additional 18 families were genotyped for these seven SSTRPs, and the complete sample of 34 families was evaluated using lod score analysis, affected pedigree member linkage analysis, and within-family association analysis. Evidence for linkage between D11S929 and affective illness remained positive, necessitating the analysis of four additional SSTRPs within 3 cM of D11S929. After all confirmatory analyses were completed, no evidence suggestive of linkage remained between any of the 38 SSTRPs and the affected phenotypes.

Depressive Disorder↗
PubMed1998

Latent structure of EEG sleep variables in depressed and control subjects: descriptions and clinical correlates.

In this study, we aimed to determine the latent structure of multiple EEG sleep variables in patients with major depressive disorder (MDD) and in healthy control subjects and to examine associations between sleep factors and clinical variables. Subjects included 109 women with MDD and 54 healthy control women. EEG sleep data were collected prior to any treatment. Principal components analysis (PCA) was conducted on a set of 24 sleep variables. Separate PCAs were run for patients with MDD, control subjects, and a matched group of patients and controls. Other analyses included correlations, t-tests and MANOVA. Each PCA identified four sleep factors that explained 70% of the total variance in individual sleep variables: slow wave sleep, REM sleep, sleep continuity and REM latency/delta sleep ratio (RL/DSR). Patients with MDD and healthy controls differed on the mean value of the sleep continuity factor, and a multivariate analysis of variance based on the PCA identified MDD-control differences in REM sleep and sleep continuity. In the MDD group, slow wave sleep correlated inversely with age and personality disorder symptoms; sleep continuity correlated with subjective sleep quality and anxiety; and RL/DSR correlated inversely with age. The mean value of the REM factor was higher among treatment non-responders than responders. EEG sleep variables have a similar latent structure in women with MDD and in healthy controls. These sleep factors are supported conceptually and empirically, and correlate with clinical measures in women with MDD. Multivariate statistical techniques decrease the risk of Type I and Type II errors when using a large number of collinear sleep measures, and can clarify conceptual issues related to sleep and depression.

Adult↗
PubMed1998

Effects of rearing condition on HPA axis response to fluoxetine and desipramine treatment over repeated social separations in young rhesus monkeys.

Normal hypothalamic-pituitary-adrenal (HPA) axis activity is disrupted in several types of human psychiatric disorders, and has been widely reported to be altered as a result of early experience in rodents. In this study the effects of early social experience on later response of the HPA axis to separations from cagemates and pharmacologic treatments were examined in rhesus monkeys. HPA axis activity was measured in mother-reared and peer-reared monkey infants in conjunction with six repeated separations from and reunions with their cagemates. Within each rearing group, infants were assigned to one of three treatment groups that received continuous treatment with either fluoxetine (2 mg/kg), desipramine (DMI, 5 mg/kg) or placebo (saline) beginning 2 weeks prior to separations. At 2 weeks after drug treatment, fluoxetine increased ACTH and cortisol in the treated groups, while DMI decreased ACTH and cortisol in both treated groups; however, these effects were not persistent over the separations. While these treatment effects tended to be more pronounced in the mother-reared group, the rearing groups did not show a clearly differential response to either of the treatments. The most prominent finding was that mother-reared monkeys showed significantly higher ACTH and cortisol levels than peer-reared monkeys over all samples, an effect that may have mitigated a potential rearing group difference in treatment response. The results add to growing evidence for the influence of primate mothers on the functional development of psychobiological systems in their infants, and suggest that the HPA axis is among the more sensitive of these systems to postnatal experience.

Adrenocorticotropic Hormone↗
PubMed1998

Delta sleep deficits in schizophrenia: evidence from automated analyses of sleep data.

BACKGROUND: Several, though not all, polysomnographic studies that use conventional visual scoring techniques show delta sleep deficits in schizophrenia. Delta sleep (in particular, > or = 1- to 2-Hz frequency range), mediated by thalamocortical circuits, is postulated to be abnormal in schizophrenia. We investigated whether deficits in delta sleep occur in schizophrenia and whether these are primarily related to the illness or are epiphenomena of previous medication use or illness chronicity. METHODS: We compared 30 unmedicated schizophrenic patients and 30 age- and sex-matched controls for sleep data evaluated by visual scoring as well as automated period amplitude analyses and power spectral analyses. RESULTS: Schizophrenic patients had reduced visually scored delta sleep. Period amplitude analyses showed significant reductions in delta wave counts but not rapid eye movement counts; power spectral analyses showed reductions in delta as well as theta power. Delta spectral power was also reduced in the subset of 19 neuroleptic-naive, first-episode schizophrenic patients compared with matched controls. Delta deficits were more pronounced in the greater than 1- to 2-Hz frequency range. CONCLUSIONS: Delta sleep deficits that occur in schizophrenia may be related to the primary pathophysiological characteristics of the illness and may not be secondary to previous neuroleptic use. Automated sleep quantification by means of period amplitude and power spectral analyses can complement the use of conventional visual scoring for understanding electrophysiological abnormalities in psychiatric disorders.

Adult↗
PubMed1998

Stressful life events and social rhythm disruption in the onset of manic and depressive bipolar episodes: a preliminary investigation.

BACKGROUND: The association between stressful life events and onset of bipolar episodes is unclear. The association between bipolar episode onset and types of life events that disrupt social routines, and potentially sleep, has not yet been investigated. METHODS: Thirty-nine bipolar patients with primarily manic (n = 20) or depressed (n = 19) index episodes were interviewed with the Bedford College Life Event and Difficulty Schedule to determine the presence of severe events during 8-week pre-onset and control periods. All life events were also rated for degree of social rhythm disruption (SRD). RESULTS: More bipolar subjects experienced at least 1 SRD event and severe event in the pre-onset vs control periods. When subjects were divided into those with manic or depressive onsets, the only significant pre-onset vs control difference was for manic patients with SRD events. Additionally, the proportion of subjects with a pre-onset SRD event was greater for manic than for depressed patients. CONCLUSIONS: We found evidence that life events characterized by SRDs routines are associated with the onset of manic, but not depressive, episodes. Severe events seem to be related to onset of bipolar episodes, although it remains unclear whether severe events relate differentially to depressive and manic onsets.

Adult↗
PubMed1998

The Pittsburgh study of normal sleep in young adults: focus on the relationship between waking and sleeping EEG spectral patterns.

The effects of age and gender on spectral characteristics of the waking EEG were investigated in a large sample of young adult men and women. In addition, relationships between spectral characteristics of the waking and sleeping EEG within an individual were explored. The sample included 28 females and 33 males in two age groups: 20-29 years (n = 32), and 30-40 years (n = 29). Spectral analysis was used to quantify EEG frequency characteristics for waking EEG just prior to sleep onset, as well as for the entire sleep recording. Significant effects of age were seen in the waking EEG but only in the delta frequency range (0.5-4.5 Hz) with lower delta activity in the older group (F = 11.6, P = 0.001). No significant gender effects were found in the waking EEG. Independent of age and gender, spectral profiles in the delta, theta, alpha and beta frequency bands of a subject's waking EEG were found to be highly correlated with their sleep EEG. In addition, subjects with high voltage alpha profiles during waking were found to sleep significantly longer and deeper than those with low voltage records. Significant correlations between waking and sleep EEG suggest that the spectral signature of an individual's EEG may be found across sleep/wake states.

Adult↗
PubMed1998

Serotonin in aging, late-life depression, and Alzheimer's disease: the emerging role of functional imaging.

Serotonin (5-HT) neuron and neurotransmitter loss in normal aging and neuropsychiatric diseases of late life may contribute to behavioral changes commonly observed in the elderly population. Extensive evidence implicates a deficit in serotonergic neurotransmission in the development of major depression. It has been further suggested that the age-related changes in 5-HT neurons may predispose the elderly to develop depression. There is also increasing evidence that a combination of disturbances in cholinergic and serotonergic function may play a role in cognitive impairment in Alzheimer's disease (AD), with serotonergic dysfunction potentially responsible for a significant portion of the behavioral aspects of the disease. This implication of the 5-HT system in aging and age-related cognitive and mood disorders rests in large part on post mortem studies and animal models, which are limited in their capacity to predict dynamic human biochemical-behavior relationships or to accurately model the living human brain. Initial applications of functional brain imaging with positron emission tomography (PET) in the in vivo study of the brain in aging depression, and dementia focused on characterizing alterations in physiological measurements of cerebral metabolism and perfusion. However, recent advances in PET radiochemistry, instrumentation, and image processing have paved the way for noninvasive means to test specific hypotheses regarding the direct involvement of 5-HT neurons in the behavioral features of aging and to define and monitor therapeutic regimens for neuropsychiatric conditions of late life. Coupling of clinical trials in well-characterized subject populations with PET imaging using ligands specific for 5-HT receptor subtypes and transporter proteins promises to increase our understanding of the role of the 5-HT system in affective and cognitive aspects of treatment response. Longitudinal studies in aging, late-life depression, and AD are also needed to evaluate the complex interplay between neurodegenerative processes and serotonergic neurotransmission.

Aged↗
PubMed1998

A method for the assessment of the functional neuroanatomy of human sleep using FDG PET.

Although sleep is characterized by relative behavioral inactivity, cortical activity is known to cycle in well-defined periods across this state. Cognitive function during sleep has been difficult to define, although disturbances in sleep are known to result from, and to cause, various human pathologies, including neuropsychiatric disorders. Assessment of brain function in humans (related to cognitive operations) during sleep has been limited, until recently, to surface electrophysiologic recordings that limit analysis of regional function, particularly in deep structures. The current report describes one method of assessing human forebrain activation during sleep using the [18F]2-fluoro-2-deoxy-d-glucose ([18F]FDG) method and positron emission tomography (PET) measures of regional cerebral glucose utilization. In comparison with other functional brain imaging techniques (e.g., assessment of blood flow or functional magnetic resonance imaging), this method offers the advantage of a more naturalistic study of sleep since subjects do not have to sleep in a scanning device. This leads to a higher rate of successful completion of studies. The primary disadvantage of this method is the decreased temporal resolution necessitating assessments of global sleep states (e.g., REM or NREM) as opposed to assessing events within a sleep state (e.g., sleep spindles or rapid eye movements).

Electroencephalography↗