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Biomedical subjects

D J Kupfer

Publications and source records attributed to D J Kupfer.

At least 73 records · Page 4Linked to original sources
PubMed1999

Pretreatment REM sleep and subjective sleep quality distinguish depressed psychotherapy remitters and nonremitters.

BACKGROUND: We compared pretreatment subjective and electroencephalographic sleep measures among depressed patients who remitted with psychotherapy alone and those who did not remit. METHODS: Patients were 111 midlife women with recurrent major depressive disorder. Baseline psychiatric ratings and sleep studies were conducted prior to treatment with weekly interpersonal psychotherapy. Remission was defined as a score of < or = 7 for 3 consecutive weeks on the Hamilton Depression Rating Scale. Clinical and sleep measures were compared between remitters (n = 62) and nonremitters (n = 49) using t tests and random regression. Linear discriminant function analyses were used to categorize remitters and nonremitters on the basis of sleep measures. RESULTS: Treatment nonremitters had significantly worse subjective sleep quality and significantly elevated phasic REM sleep as measured by multivariate and univariate analyses. The linear accumulation of REM activity during sleep occurred at a significantly higher rate in nonremitters than in remitters. Linear discriminant function analyses based on subjective sleep quality and REM activity correctly identified 68.3% of nonremitters and 68.5% of remitters. CONCLUSIONS: These findings highlight the role of subjective and REM sleep measures as correlates of short-term psychotherapy treatment response in major depressive disorder. Disturbed sleep may be a physiological indicator of increased limbic and brain stem arousal.

Adult↗
PubMed1999

Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression: a randomized controlled trial in patients older than 59 years.

CONTEXT: Elderly patients with major depression are at high risk for recurrence, increased mortality, and chronic disability. OBJECTIVE: To determine the efficacy of maintenance nortriptyline hydrochloride and interpersonal psychotherapy (IPT) in preventing recurrence of major depressive episodes in patients older than 59 years. DESIGN: A 2 x 2 randomized, double-blind, placebo-controlled clinical trial, stratified by therapist. SETTING: University-based psychiatric research clinic. PATIENTS: Of a total of 187 patients with recurrent nonpsychotic unipolar major depression (average age, 67 years; one third aged > or =70 years) recruited through clinical referral and media announcements, 107 were fully recovered after open acute and treatment continuation with nortriptyline and IPT. These patients were randomly assigned to 1 of 4 maintenance therapy conditions. INTERVENTIONS: Monthly medication clinic with nortriptyline hydrochloride (80-120 ng/mL steady-state levels) (n = 24); medication clinic with placebo (n = 29); monthly maintenance IPT with placebo (n = 21); and monthly maintenance IPT with nortriptyline (n = 22). MAIN OUTCOME MEASURE: Recurrence of major depressive episode. RESULTS: The time to recurrence of a major depressive episode for all 3 active treatments was significantly better than for placebo. Recurrence rates over 3 years were as follows: nortriptyline and IPT, 20% (95% confidence interval [CI], 4%-36%); nortriptyline and medication clinic visits, 43 % (95% CI, 25%-61%); IPT and placebo, 64% (95% CI, 45%-83%); and placebo and medication clinic visits, 90% (95% CI, 79%-100%). Combined treatment with nortriptyline and IPT was superior to IPT and placebo and showed a trend to superior efficacy over nortriptyline monotherapy (Wald chi2 = 3.56; P = .06). Subjects aged 70 years and older had a higher and more rapid rate of recurrence than those aged 60 to 69 years. CONCLUSION: In geriatric patients with recurrent major depression, maintenance treatment with nortriptyline or IPT is superior to placebo in preventing or delaying recurrence. Combined treatment using both appears to be the optimal clinical strategy in preserving recovery.

Adrenergic Uptake Inhibitors↗
PubMed1999

Adjunctive antipsychotic use in bipolar patients: an open 6-month prospective study following an acute episode.

BACKGROUND: We examined the use of adjunctive antipsychotics in the treatment of bipolar patients. METHODS: A total of 88 bipolar type I patients (DSM-IV diagnosis) were included. The patterns of adjunctive antipsychotic use in the first 6 months after an index episode were examined. RESULTS: A total of 34 patients (39%) received at least one antipsychotic during the follow-up period. At time 0, 23 subjects (26%) were on antipsychotics; at 3 months, 10 subjects (11%); and at the end of the 6 month period, 11 subjects (12%). Prolonged use of antipsychotics (more than 15 weeks) was found in eight patients (9%). No significant differences were found in demographic characteristics or baseline clinical variables between the patients who received or did not receive antipsychotics, except that the use of adjunct antipsychotics in the 6-month period was significantly more common after an index manic than depressive episode (68 versus 17%, respectively, P = 0.001; Fisher's exact test). LIMITATIONS: This report presents a secondary analysis of follow-up data from a prospective study, and therefore the hypotheses here examined were not originally part of the primary hypotheses that led to the design of the study. A larger sample size could eventually reveal small differences among the patient sub-groups not presently found. CONCLUSIONS: The use of adjunctive antipsychotics among bipolar patients was less extensive than previously reported, and mostly related to an index manic episode. Our findings suggest that in samples of carefully diagnosed bipolar type I patients the group that may need continued antipsychotic treatment is relatively small.

Acute Disease↗
PubMed1999

Residual analysis in random regressions using SAS and S-PLUS.

A program package RRAP: Random Regression Residual Analysis Program using SAS [1] and S-PLUS [2] is available for performing random regression residual analysis. The PROCEDURE MIXED from SAS is used for statistical inference. Both elementary-level and individual-level residuals are used. The S-PLUS programs provide: (1) a transformation to orthogonalize the elementary-level correlated residuals for standard regression residual analyses; and (2) several statistics and plots for checking model assumptions, assessing model fitting and detecting outlying individuals. RRRAP starts with a SAS Macro RRRAPMAC on the data followed by a S-PLUS Program DoRRRAP on a UNIX system.

Models, Statistical↗
PubMed1999

Effects of prior fluoxetine treatment on EEG sleep in women with recurrent depression.

We examined whether fluoxetine treatment has persistent effects on electroencephalographic sleep after drug discontinuation in patients with recurrent major depression. Age-matched groups of 23 women were treated with interpersonal psychotherapy alone (IPT) or fluoxetine plus interpersonal psychotherapy (IPT + FLU). Sleep studies were conducted when patients were depressed, and again at remission, at least four weeks after fluoxetine discontinuation. The groups did not differ in depression ratings pre- to post-treatment. Significant group*time interaction effects were noted for REM sleep (p = .04) and slow wave sleep (p = .02). REM percentage and phasic REM activity increased in the IPT + FLU group but decreased in the IPT group. The effects of fluoxetine treatment on electroencephalographic sleep can be observed for at least four weeks after drug discontinuation and appear to represent both drug discontinuation and neuroadaptation effects.

Adult↗
PubMed1999

PET measures of amphetamine-induced dopamine release in ventral versus dorsal striatum.

Regional differences in dextroamphetamine (AMPH)-induced dopamine (DA) release in the baboon striatum were assessed using positron emission tomographic (PET) measures of [11C]raclopride specific binding to DA D2/D3 receptors acquired before and after AMPH administration. The magnitude of the reduction in [11C]raclopride binding, following AMPH administration, was two-fold greater in the anteroventral striatum (comprised of ventral caudate, anteroventral putamen, and nucleus accumbens) than the dorsal striatum (dorsal caudate). A simulation study demonstrated that any potential biases due to resolution (partial volume) and alignment effects were significantly smaller than the magnitude of the observed results. These regional differences in the sensitivity of AMPH are compatible with microdialysis evidence in rats indicating that the magnitude of DA release in response to AMPH concentrations in the range tested is greater in ventral than dorsal striatal regions. Post hoc tests involving measures in other striatal regions showed that the baseline DA D2/D3 binding was highest and the correlation between AMPH dose and change in [11C]raclopride binding most significant in the putamen.

Amphetamine↗
PubMed1999

Pathophysiology and management of insomnia during depression.

Depressed patients often report problems sleeping, and epidemiologic evidence suggests that insomnia may precede the onset of depression. Insomnia is associated with marked impairment in quality of life and ability to function effectively. Many studies have indicated that patients with chronic sleep problems have impaired mood and that effective management of insomnia in depressed patients can markedly improve their depression. Diagnosis of insomnia is challenging because there can be many different causes and the clinical picture can be blurred by the presence of other psychiatric illnesses. Pharmacotherapy provides reliable and rapid relief from insomnia, whereas behavioral therapies help produce long-term improvement. For many years, benzodiazepines have been the mainstay of drug treatment for insomnia. However, these drugs have significant side effects, and tolerance and dependence have discouraged use. Many doctors use sedating antidepressants in low doses to treat chronic insomnia. However, there is little evidence supporting the efficacy of these agents, and many have adverse side effects, including impairment of sleep. The newer selective hypnotic drugs, including the imidazopyridines, may offer patients a better short-term alternative to benzodiazepines or sedating antidepressants.

Anti-Anxiety Agents↗
PubMed1999

Adjunctive psychotherapy for bipolar disorder: effects of changing treatment modality.

In a randomized, controlled trial, the authors studied an adjunctive, individual psychotherapy, interpersonal and social rhythm therapy (IPSRT) for bipolar disorder. After stabilizing participants with episode appropriate pharmacotherapy and either IPSRT or intensive clinical management (CM), participants were reassigned to IPSRT or CM in conjunction with pharmacotherapy for 2 years of preventative treatment. Early results (n = 82) suggest that altering participants' treatment assignment at entry to the preventative phase is related to risk of recurrence. Participants remaining in the same treatment for both acute and preventative phases had lower rates of recurrence (< 20% vs. > 40%) and levels of symptomatology over the subsequent 52 weeks than those reassigned to the alternate modality. This finding, consistent with the authors' philosophy that bipolar patients benefit from stable routines, suggests that disruptions in the psychosocial treatment plan contribute to worse outcomes.

Adult↗
PubMed1999

The MacArthur Three-City Outcome Study: evaluating multi-informant measures of young children's symptomatology.

OBJECTIVE: Three sites collaborated to evaluate the reliability and validity of 2 measures, developed in tandem to assess symptomatology and impairment in 4- to 8-year-old children: the Berkeley Puppet Interview Symptomatology Scales (BPI-S) and the Health and Behavior Questionnaire (HBQ). METHOD: In this case-control study, mothers, teachers, and children reported on multiple dimensions of children's mental health for 120 children (67 community and 53 clinic-referred children). RESULTS: The BPI-S and the parent and teacher versions of the HBQ demonstrated strong test-retest reliability and discriminant validity on a majority of symptom scales. Medium to strong effect sizes (Cohen d) indicated that children in the clinic-referred group were viewed by all 3 informants as experiencing significantly higher levels of symptomatology than nonreferred, community children. CONCLUSION: The availability of a set of multi-informant instruments that are psychometrically sound, developed in tandem, and developmentally appropriate for young children will enhance researchers' ability to investigate and understand symptomatology or the emergence of symptomatology in middle childhood.

Case-Control Studies↗
PubMed1999

Influence of traumatic grief on suicidal ideation among young adults.

OBJECTIVE: The purpose of this study was to examine the influence of traumatic grief on suicidal ideation. METHOD: The Beck-Kovacs Scale for Suicidal Ideation was administered to 76 young adult friends of suicide victims. RESULTS: Traumatic grief was associated with a 5.08 times greater likelihood of suicidal ideation, after control for depression. Comorbid traumatic grief and depression were not associated with a greater likelihood of suicidal ideation. CONCLUSIONS: Syndromal traumatic grief heightens vulnerability to suicidal ideation.

Adult↗
PubMed1999

Treatment of bereavement-related major depressive episodes in later life: a controlled study of acute and continuation treatment with nortriptyline and interpersonal psychotherapy.

OBJECTIVE: The authors tested the hypothesis that nortriptyline and interpersonal psychotherapy, alone and in combination, are superior to placebo in achieving remission of bereavement-related major depressive episodes. METHOD: Eighty subjects, aged 50 years and older, with major depressive episodes that began within 6 months before or 12 months after the loss of a spouse or significant other were randomly assigned to a 16-week doubleblind trial of one of four treatment conditions: nortriptyline plus interpersonal psychotherapy (N = 16), nortriptyline alone in a medication clinic (N = 25), placebo plus interpersonal psychotherapy (N = 17), or placebo alone in a medication clinic (N = 22). The protocol required that the acute-phase double-blind treatment be ended after 8 weeks if Hamilton depression scale ratings had not improved by 50%. Remission was defined as a 17-item Hamilton scale score of 7 or lower for 3 consecutive weeks. RESULTS: The rate of remission for nortriptyline plus interpersonal psychotherapy was 69% (N = 11); for medication clinic, nortriptyline, 56% (N = 14); for placebo plus interpersonal psychotherapy, 29% (N = 5); and for medication clinic, placebo, 45% (N = 10). In a generalized logit model, there was a significant effect of nortriptyline over placebo but no interpersonal psychotherapy effect and no nortriptyline-by-interpersonal psychotherapy interaction. Rates of all-cause attrition were lowest in the nortriptyline plus interpersonal psychotherapy group. CONCLUSIONS: Nortriptyline was superior to placebo in achieving remission of bereavement-related major depressive episodes. The combination of medication and psychotherapy was associated with the highest rate of treatment completion. These results support the use of pharmacologic treatment of major depressive episodes in the wake of a serious life stressor such as bereavement.

Aged↗
PubMed1999

Cerebral glucose metabolic response to combined total sleep deprivation and antidepressant treatment in geriatric depression.

OBJECTIVE: The treatment of geriatric depression is complicated by a variable and delayed response to antidepressant treatment. The present study was undertaken to test the hypothesis that combined total sleep deprivation and paroxetine treatment would produce a persistent reduction in glucose metabolism in the anterior cingulate cortex similar to that reported after long-term antidepressant treatment. METHOD: Six elderly depressed patients who met the DSM-IV criteria for major depressive disorder and six age-matched comparison subjects underwent serial positron emission tomography (PET) studies at baseline, after total sleep deprivation, after recovery sleep (after the initial paroxetine dose), and after 2 weeks of paroxetine treatment (patients only). The PET data were analyzed by using statistical parametric mapping methods. RESULTS: The patients' scores on a 13-item version of the Hamilton Depression Rating Scale were decreased after total sleep deprivation, after recovery sleep, and after 2 weeks of treatment. The Hamilton depression scores of the comparison subjects were not significantly altered. In the patients, the greatest reductions in normalized, relative glucose metabolism after sleep deprivation were observed in the anterior cingulate cortex (Brodmann area 24), and they persisted after recovery sleep and antidepressant treatment. The comparison subjects demonstrated increased metabolism in these areas. CONCLUSIONS: Improvement in the patients' depressive symptoms was accompanied by reduced glucose metabolism in the right anterior cingulate cortex and right medial frontal cortex. These preliminary data indicate that in elderly depressed patients, total sleep deprivation may accelerate the clinical and glucose metabolic response to antidepressant treatment.

Age Factors↗
PubMed1999

Therapeutic drug monitoring of mood stabilizers in Medicaid patients with bipolar disorder.

OBJECTIVE: The authors' goal was to determine the extent and pattern of blood serum monitoring of mood stabilizers in Medicaid patients with bipolar disorder. METHOD: Data were drawn from a Medicaid medical claims data set from Pittsburgh and the surrounding region. The authors identified bipolar patients using lithium, valproate, and carbamazepine (N = 718) and then examined the patient demographic, diagnostic, and service use variables associated with therapeutic drug monitoring. RESULTS: A substantial proportion of lithium users (36.5%), valproate users (42.4%), and carbamazepine users (42.2%) with bipolar disorder diagnoses did not receive therapeutic drug level testing during the 12-month study period. Carbamazepine users who were male or in the 30-49-year age range were significantly less likely to be tested for serum drug level. Lithium users who did not receive partial-hospitalization psychiatric services and valproate users who received mental health case management were also less likely to be tested for serum drug level. Over one-half of the lithium users (54.1%) did not receive thyroid function tests, and few (4.2%) received renal function tests. Patients who did receive tests for serum drug level were likely to receive the other recommended tests. CONCLUSIONS: Many Medicaid patients with bipolar disorder received no therapeutic drug monitoring. Patient sociodemographic characteristics contributed little to explaining this omission, although some types of service utilization were related to rates of serum drug level testing.

Adolescent↗
PubMed1999

Three-year outcomes of maintenance nortriptyline treatment in late-life depression: a study of two fixed plasma levels.

OBJECTIVE: This study compared the long-term efficacy of two fixed plasma levels of nortriptyline in preventing or delaying recurrence of major depression in elderly patients and in minimizing residual depressive symptoms and somatic complaints. METHOD: The authors randomly assigned 41 elderly patients with histories of recurrent major depression to 3-year, double-blind maintenance pharmacotherapy using nortriptyline, with controlled plasma concentrations of 80-120 ng/ml versus 40-60 ng/ml. The authors compared times to, and rates of, recurrence of major depression. They also compared frequencies of side effects, noncompliance episodes, and subsyndromal symptomatic flare-ups. RESULTS: Major depressive episodes recurred for six (29%) of 21 subjects in the 80-120-ng/ml condition and eight (40%) of 20 subjects in the 40-60-ng/ml condition, a nonsignificant difference. Most recurrences took place in the first year of maintenance treatment. Hamilton depression scores in the subsyndromal range (higher than either 10 or 7) occurred significantly more often at 40-60 ng/ml, while constipation occurred significantly more often at 80-120 ng/ml. The proportions of patients reporting missed doses did not differ. CONCLUSIONS: Maintenance pharmacotherapy with nortriptyline at 80-120 ng/ml is associated with fewer residual depressive symptoms, that is, a less variable long-term response, than pharmacotherapy at 40-60 ng/ml, but constipation is more frequent and there is no difference in recurrence of syndromal major depressive episodes. Treatment at 80-120 ng/ml may be preferable, because of fewer residual symptoms and less variability of response, as long as side effect burden can be managed successfully.

Aged↗
PubMed1999

Competence of depressed patients for consent to research.

OBJECTIVE: The capacities of depressed patients to consent to research have been questioned by commentators who fear that the cognitive effects of a disorder may impair subjects' abilities to protect their interests. This study used a new instrument for assessing depressed patients' capacities to consent to research and examined their performance, including the relation between severity of depression and extent of impairment. METHOD: Twenty-six female outpatients with major depression (assessed with the Schedule of Affective Disorders and Schizophrenia-Lifetime Version) enrolled in a study of maintenance psychotherapy were recruited for this project. Consent-related abilities were measured with the MacArthur Competence Assessment Tool-Clinical Research (MacCAT-CR) 1 week after intake and again 8-10 weeks later. Depressive symptoms were measured by the Hamilton Depression Rating Scale. RESULTS: Almost all subjects performed quite well on the capacity measures and maintained that level of performance over time. There was no correlation between performance and degree of depressive symptoms and little relation to prior research experience. Some subjects appeared confused about the extent to which decisions about assignment to treatment groups would be made on the basis of their clinical condition rather than randomly. CONCLUSIONS: This outpatient group with major depression showed few impairments in their decision-making capacities related to research. As in other studies, some concerns were raised about subjects' appreciation that treatment assignments would not be individualized for their needs. Examination of hospitalized patients and those with psychotic depression would help to determine whether they show greater degrees of impairment. The MacCAT-CR was easily adapted for use with this depressed group.

Adult↗
PubMed1999

Depression and aging: a look to the future.

Geriatric depression is widespread, affecting at least one of six patients treated in general medical practice and an even higher percentage in hospitals and nursing homes. Depression in later life has serious consequences, including patients' and caregivers' distress, amplification of disability associated with medical and cognitive disorders of later life, increased health care costs, and increased mortality related to suicide and medical illness. Despite the numerous pathways to late-life depression, as well as the complex medical and psychosocial context in which it occurs, it can be effectively diagnosed and treated. To meet the public health challenges posed by geriatric depression over the next 15 years, the major priorities for research and clinical practice must include improvement in recognizing and treating depression among elderly patients seen in the general medical sector, suicide prevention among elderly patients seen in primary care, and acceleration of response to antidepressants. Other major priorities include improving the early recognition of treatment resistance in late-life depression and developing strategies for improving the treatment response of such patients; finding maintenance treatments with long-term efficacy, especially for patients over age 70 and those who have required electroconvulsive therapy; and developing preventive strategies to reduce the liability to late-onset depression.

Age Factors↗