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Biomedical subjects

Harold A Sackeim

Publications and source records attributed to Harold A Sackeim.

At least 19 recordsLinked to original sources
PubMed2006

Deep brain stimulation in movement and psychiatric disorders.

Deep brain stimulation (DBS) is the most focal and invasive of the electromagnetic brain stimulation therapies. A subcutaneous pulse generator provides continuous stimulation of circumscribed brain tissue via a multicontact microelectrode that terminates within its target. The result is an adjustable, reversible, and specific therapy. Despite limited understanding of its mechanisms of action, DBS efficacy has been established in several movement disorders, and promising reports have emerged for Tourette syndrome, obsessive-compulsive disorder, and major depression. Deep brain stimulation may prove to be a reasonable option for severely ill and treatment-resistant patients who otherwise have limited therapeutic options and a poor prognosis.

Animals↗
PubMed2006

Vascular depression: A distinct diagnostic subtype?

Vascular depression has been proposed as a unique and valid diagnostic subtype on the basis of studies of external (concurrent and predictive) validity. Validating a diagnostic entity on the basis of external validity is problematic, because it presupposes that the construct is well defined (i.e., the proposed features cluster together to define a distinct patient group). Because such evidence has not been obtained, we propose that the next critical step in evaluating this potential subtype is to establish internal (construct) validity and highlight taxometric analysis and latent class cluster analysis as illustrative multivariate statistical techniques that can be used in this effort. The psychometric approach advocated here (despite its inherent assumptions and limitations) might substantially improve on previous diagnostic efforts (e.g., expert consensus), and vascular depression might serve as a prototype for future psychiatric classification.

Cerebrovascular Disorders↗
PubMed2006

The cognitive effects of electroconvulsive therapy in community settings.

Despite ongoing controversy, there has never been a large-scale, prospective study of the cognitive effects of electroconvulsive therapy (ECT). We conducted a prospective, naturalistic, longitudinal study of clinical and cognitive outcomes in patients with major depression treated at seven facilities in the New York City metropolitan area. Of 751 patients referred for ECT with a provisional diagnosis of a depressive disorder, 347 patients were eligible and participated in at least one post-ECT outcome evaluation. The primary outcome measures, Modified Mini-Mental State exam scores, delayed recall scores from the Buschke Selective Reminding Test, and retrograde amnesia scores from the Columbia University Autobiographical Memory Interview-SF (AMI-SF), were evaluated shortly following the ECT course and 6 months later. A substantial number of secondary cognitive measures were also administered. The seven sites differed significantly in cognitive outcomes both immediately and 6 months following ECT, even when controlling for patient characteristics. Electrical waveform and electrode placement had marked cognitive effects. Sine wave stimulation resulted in pronounced slowing of reaction time, both immediately and 6 months following ECT. Bilateral (BL) ECT resulted in more severe and persisting retrograde amnesia than right unilateral ECT. Advancing age, lower premorbid intellectual function, and female gender were associated with greater cognitive deficits. Thus, adverse cognitive effects were detected 6 months following the acute treatment course. Cognitive outcomes varied across treatment facilities and differences in ECT technique largely accounted for these differences. Sine wave stimulation and BL electrode placement resulted in more severe and persistent deficits.

Adult↗
PubMed2006

Report by the ACNP Task Force on response and remission in major depressive disorder.

This report summarizes recommendations from the ACNP Task Force on the conceptualization of remission and its implications for defining recovery, relapse, recurrence, and response for clinical investigators and practicing clinicians. Given the strong implications of remission for better function and a better prognosis, remission is a valid, clinically relevant end point for both practitioners and investigators. Not all depressed patients, however, will reach remission. Response is a less desirable primary outcome in trials because it depends highly on the initial (often single) baseline measure of symptom severity. It is recommended that remission be ascribed after 3 consecutive weeks during which minimal symptom status (absence of both sadness and reduced interest/pleasure along with the presence of fewer than three of the remaining seven DSM-IV-TR diagnostic criterion symptoms) is maintained. Once achieved, remission can only be lost if followed by a relapse. Recovery is ascribed after at least 4 months following the onset of remission, during which a relapse has not occurred. Recovery, once achieved, can only be lost if followed by a recurrence. Day-to-day functioning and quality of life are important secondary end points, but they were not included in the proposed definitions of response, remission, recovery, relapse, or recurrence. These recommendations suggest that symptom ratings that measure all nine criterion symptom domains to define a major depressive episode are preferred as they provide a more certain ascertainment of remission. These recommendations were based largely on logic, the need for internal consistency, and clinical experience owing to the lack of empirical evidence to test these concepts. Research to evaluate these recommendations empirically is needed.

Clinical Trials as Topic↗
PubMed2006

Determining the duration of antidepressant treatment: application of signal detection methodology and the need for duration adaptive designs (DAD).

BACKGROUND: With remission now the treatment goal, antidepressant trial duration has increased. However, most patients do not remit and are exposed to prolonged, ineffective treatment. METHODS: Conditional probabilities and signal detection methodology were contrasted in early detection of nonremitters in three comparator, 12-week antidepressant trials conducted in late- or mid-life depression. RESULTS: The mid- and late-life samples did not differ in rates or time-to-onset of remission or accuracy of early identification of nonremission. Using conditional probabilities, there were marked differences in predictive power depending on the remission criterion. With signal detection methods, sensitivity and specificity of early identification were uniform across the differing medication conditions, remission criteria, and the three studies. By week 6, > or = 60% of ultimate nonremitters were identified, while maintaining a false positive rate < or = 20%. CONCLUSIONS: The goals of providing maximal opportunity to achieve remission, while minimizing exposure to ineffective treatment can be satisfied by use of duration adaptive designs (DAD). While use of conditional probabilities has been the traditional method for early detection of nonremitters, this approach is inferior to use of signal detection methods. The findings also contradicted the widely held view that patients with late-life depression require longer treatment duration.

Antidepressive Agents, Second-Generation↗
PubMed2006

WAIS-III and WMS-III performance in chronic Lyme disease.

There is controversy regarding the nature and degree of intellectual and memory deficits in chronic Lyme disease. In this study, 81 participants with rigorously diagnosed chronic Lyme disease were administered the newest revisions of the Wechsler Adult Intelligence Scale (WAIS-III) and Wechsler Memory Scale (WMS-III), and compared to 39 nonpatients. On the WAIS-III, Lyme disease participants had poorer Full Scale and Performance IQ's. At the subtest level, differences were restricted to Information and the Processing Speed subtests. On the WMS-III, Lyme disease participants performed more poorly on Auditory Immediate, Immediate, Auditory Delayed, Auditory Recognition Delayed, and General Memory indices. Among WMS-III subtests, however, differences were restricted to Logical Memory (immediate and delayed) and Family Pictures (delayed only), a Visual Memory subtest. Discriminant analyses suggest deficits in chronic Lyme are best characterized as a combination of memory difficulty and diminished processing speed. Deficits were modest, between one-third and two-thirds of a standard deviation, consistent with earlier studies. Depression severity had a weak relationship to processing speed, but little other association to test performance. Deficits in chronic Lyme disease are consistent with a subtle neuropathological process affecting multiple performance tasks, although further work is needed to definitively rule out nonspecific illness effects.

Adult↗
PubMed2006

The WAIS-III and major depression: absence of VIQ/PIQ differences.

Poor Performance IQ (PIQ) relative to Verbal IQ (VIQ) is a standard finding in depressed patients administered the Wechsler Adult Intelligence Scale-Revised (WAIS-R). This study examined performance of depressed subjects on the instrument's latest revision, the WAIS-III, which provides a more detailed subdomain profile of intellectual functioning. WAIS-III IQ, index and subscale scores were compared between 121 unmedicated subjects in major depressive episode and 41 healthy volunteers, using demographically adjusted T-score conversions. Depressed subjects had significantly lower PIQ scores, but neither the absolute VIQ/PIQ difference nor prevalence of VIQ/PIQ discrepancies >1 SD differed between groups. Index score differences were exclusively in Processing Speed, and subtest differences only on timed tasks. WAIS-III scores did not differ between subjects with major depressive and bipolar disorders, nor between subjects with and without melancholia or history of suicidal behavior. Results suggest general intellectual performance in depression is best characterized by deficits in processing speed, rather than global nonverbal abilities, and that this deficit is consistent across depression subtypes.

Adult↗
PubMed2006

Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report.

OBJECTIVE: This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. METHOD: A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N=3,671) to four (N=123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to move to the next step. Those with an acceptable benefit, preferably symptom remission, from any particular step could enter a 12-month naturalistic follow-up phase. A score of or=11 (HRSD(17)>or=14) defined relapse. RESULTS: The QIDS-SR(16) remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, third, and fourth acute treatment steps, respectively. The overall cumulative remission rate was 67%. Overall, those who required more treatment steps had higher relapse rates during the naturalistic follow-up phase. In addition, lower relapse rates were found among participants who were in remission at follow-up entry than for those who were not after the first three treatment steps. CONCLUSIONS: When more treatment steps are required, lower acute remission rates (especially in the third and fourth treatment steps) and higher relapse rates during the follow-up phase are to be expected. Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed.

Adolescent↗
PubMed2006

Factors associated with health-related quality of life among outpatients with major depressive disorder: a STAR*D report.

OBJECTIVE: Major depressive disorder (MDD) is often chronic and is often associated with significant morbidity and mortality. The importance of assessing disability and health-related quality of life (HRQOL) in patients with MDD has only recently been recognized. The aim of this study was to examine sociodemographic and clinical correlates of HRQOL in a large cohort of outpatients with MDD. METHOD: Baseline assessments were completed for 1500 consecutive patients enrolled in the Sequenced Treatment Alternatives to Relieve Depression trial, including sociodemographic characteristics and measures of depressive symptom severity, clinical features, and HRQOL. Multiple domains of HRQOL were assessed with the 12-item Short Form Health Survey, the Work and Social Adjustment Scale, and the Quality of Life Enjoyment and Satisfaction Questionnaire. The current analyses were conducted on HRQOL data available for 1397 of the 1500 subjects. RESULTS: Greater symptom severity was associated with reduced HRQOL by all measures. Even after age and symptom severity were controlled for, a number of clinical features and sociodemographic characteristics were independently associated with HRQOL in multiple domains, including age at onset of MDD, ethnicity, marital status, employment status, education level, insurance status, and monthly household income. CONCLUSION: Results strongly suggest the need to assess HRQOL in addition to symptoms in order to gauge the true severity of MDD. This study also highlights the necessity of measuring HRQOL in multiple domains. These results have implications for the assessment of remission and functional recovery in the treatment of MDD.

Adult↗
PubMed2005

Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study.

BACKGROUND: The need for effective, long-term treatment for recurrent or chronic, treatment-resistant depression is well established. METHODS: This naturalistic follow-up describes outpatients with nonpsychotic major depressive (n = 185) or bipolar (I or II) disorder, depressed phase (n = 20) who initially received 10 weeks of active (n = 110) or sham vagus nerve stimulation (VNS) (n = 95). The initial active group received another 9 months, while the initial sham group received 12 months of VNS. Participants received antidepressant treatments and VNS, both of which could be adjusted. RESULTS: The primary analysis (repeated measures linear regression) revealed a significant reduction in 24-item Hamilton Rating Scale for Depression (HRSD(24)) scores (average improvement, .45 points [SE = .05] per month (p < .001). At exit, HRSD(24) response rate was 27.2% (55/202); remission rate (HRSD(24) < or = 9) was 15.8% (32/202). Montgomery Asberg Depression Rating Scale (28.2% [57/202]) and Clinical Global Impression-Improvement (34.0% [68/200]) showed similar response rates. Voice alteration, dyspnea, and neck pain were the most frequently reported adverse events. CONCLUSIONS: These 1-year open trial data found VNS to be well tolerated, suggesting a potential long-term, growing benefit in treatment-resistant depression, albeit in the context of changes in depression treatments. Comparative long-term data are needed to determine whether these benefits can be attributed to VNS.

Adult↗
PubMed2005

Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial.

BACKGROUND: Vagus nerve stimulation (VNS) alters both concentrations of neurotransmitters or their metabolites and functional activity of central nervous system regions dysregulated in mood disorders. An open trial has suggested efficacy. METHODS: This 10-week, acute, randomized, controlled, masked trial compared adjunctive VNS with sham treatment in 235 outpatients with nonpsychotic major depressive disorder (n = 210) or nonpsychotic, depressed phase, bipolar disorder (n = 25). In the current episode, participants had not responded adequately to between two and six research-qualified medication trials. A two-week, single-blind recovery period (no stimulation) and then 10 weeks of masked active or sham VNS followed implantation. Medications were kept stable. Primary efficacy outcome among 222 evaluable participants was based on response rates (>/=50% reduction from baseline on the 24-item Hamilton Rating Scale for Depression [HRSD(24)]). RESULTS: At 10-weeks, HRSD(24) response rates were 15.2% for the active (n = 112) and 10.0% for the sham (n = 110) groups (p = .251, last observation carried forward [LOCF]). Response rates with a secondary outcome, the Inventory of Depressive Symptomatology - Self-Report (IDS-SR(30)), were 17.0% (active) and 7.3% (sham) (p = .032, LOCF). VNS was well tolerated; 1% (3/235) left the study because of adverse events. CONCLUSIONS: This study did not yield definitive evidence of short-term efficacy for adjunctive VNS in treatment-resistant depression.

Adult↗
PubMed2005

A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression.

BACKGROUND: Previous reports have described the effects of vagus nerve stimulation plus treatment as usual (VNS+TAU) during open trials of patients with treatment-resistant depression (TRD). To better understand these effects on long-term outcome, we compared 12-month VNS+TAU outcomes with those of a comparable TRD group. METHODS: Admission criteria were similar for those receiving VNS+TAU (n = 205) or only TAU (n = 124). In the primary analysis, repeated-measures linear regression was used to compare the VNS+TAU group (monthly data) with the TAU group (quarterly data) according to scores of the 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR(30)). RESULTS: The two groups had similar baseline demographic data, psychiatric and treatment histories, and degrees of treatment resistance, except that more TAU participants had at least 10 prior major depressive episodes, and the VNS+TAU group had more electroconvulsive therapy before study entry. Vagus nerve stimulation plus treatment as usual was associated with greater improvement per month in IDS-SR(30) than TAU across 12 months (p < .001). Response rates according to the 24-item Hamilton Rating Scale for Depression (last observation carried forward) at 12 months were 27% for VNS+TAU and 13% for TAU (p < .011). Both groups received similar TAU (drugs and electroconvulsive therapy) during follow-up. CONCLUSIONS: This comparison of two similar but nonrandomized TRD groups showed that VNS+TAU was associated with a greater antidepressant benefit over 12 months.

Adolescent↗
PubMed2005

Randomized controlled trial of the cognitive side-effects of magnetic seizure therapy (MST) and electroconvulsive shock (ECS).

Magnetic seizure therapy (MST) is under development as a means of improving the cognitive side-effect profile of electroconvulsive therapy (ECT) by inducing more spatially delimited seizures that spare cortical regions involved in memory. We tested whether MST had a cognitive side-effect profile distinct from electroconvulsive shock (ECS) in a non-human primate model, using the Columbia University Primate Cognitive Profile, which has been shown to be sensitive to the cognitive effects of ECS. Using a within-subject cross-over design, daily ECS, MST, and sham (anaesthesia-only) interventions were administered in 5-wk blocks. Rhesus macaques (n = 2) were trained on a long-term memory task, an anterograde learning and memory task, and a combined anterograde and retrograde task where learning and memory were evaluated for new and previously learned 3-item lists. Acutely following each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-h retention interval. Overall, monkeys were least accurate following ECS (p's < 0.05) compared to sham and MST. This effect was most marked for long-term memory of a constant target, short-term memory of a variable target and recall of previously learned 3-item lists. Monkeys were slowest to complete all tasks following ECS (p's = 0.0001). Time to task completion following MST did not differ from sham. These findings suggest that MST results in a more benign acute cognitive side-effect profile than ECS in this model, consistent with initial observations with human MST.

Amnesia, Anterograde↗
PubMed2005

Correlates of trait impulsiveness in performance measures and neuropsychological tests.

Performance measures of impulsiveness offer great promise for assessing this trait in clinical and experimental studies. However, little is known about their relative superiority or inferiority to standard cognitive performance measures as correlates of this trait. In this study, 58 healthy volunteers completed a self-rating of impulsiveness (Barratt Impulsiveness Scale) and a battery of neuropsychological tests. The test battery included measures of reaction time, attention, memory, fluency, and executive function, as well as two performance measures of impulsiveness--Time Estimation and a Go-No Go task. Self-ratings correlated moderately with a number of these test scores, but many correlations became non-significant after adjustment for age and education. Correlations with the Go-No Go task, verbal fluency, executive function measures (Trails B), and tasks requiring decision-making against time (Choice Reaction Time, Reaction Time to Paired Words and Paired Faces Memory Tasks, and response bias on the Continuous Performance Test) remained significant. Performance on the Go-No Go task was the strongest correlate of self-rated impulsiveness. The findings suggest that once general demographic or ability factors are accounted for, specialized performance tasks requiring decision-making and response organization under time pressure provide the most effective means of assessing this behavioral trait.

Adult↗
PubMed2005

Optimal length of antidepressant trials in late-life depression.

There is a long-standing belief that elderly patients take longer to respond to antidepressant treatment than younger patients, and thus, require longer trials to respond or remit. This has led to the question: What is the minimum duration of antidepressant treatment necessary to identify responders in older depressed adults? A 12-week duration was tested based on 2 separate ideas: (1) older patients take longer to respond and, therefore, require longer trials to achieve optimal response (ie, remission), and (2) patients who are still quite symptomatic at Week 11 may improve dramatically and meet response, or even remission, criteria by Week 12. The data that support these beliefs are sparse and what little exist are contradictory. Rates of response and time-to-response were analyzed in depressed older adults in two 12-week clinical trials. The results do not support the belief that older patients take longer to respond or that, generally, as a group, older patients have a lower response rate. Furthermore, if patients do not have > or =30% reduction in baseline Hamilton Rating Score for Depression (HRSD) by Week 4, the probability that they will meet remission criteria (defined as HRSD < or =10 and HRSD < or =6) at the end of the trial is only 35% and 16.5%, respectively. Therefore, a 12-week trial is not necessary for all older patients; rather, the degree of improvement in the first 4 to 6 weeks identifies patients who are highly likely to benefit from continuing antidepressant treatment as well as those who very probably should have their treatment regimen altered at that point.

Age Factors↗
PubMed2005

A new approach to spatial covariance modeling of functional brain imaging data: ordinal trend analysis.

In neuroimaging studies of human cognitive abilities, brain activation patterns that include regions that are strongly interactive in response to experimental task demands are of particular interest. Among the existing network analyses, partial least squares (PLS; McIntosh, 1999; McIntosh, Bookstein, Haxby, & Grady, 1996) has been highly successful, particularly in identifying group differences in regional functional connectivity, including differences as diverse as those associated with states of awareness and normal aging. However, we address the need for a within-group model that identifies patterns of regional functional connectivity that exhibit sustained activity across graduated changes in task parameters. For example, predictions of sustained connectivity are commonplace in studies of cognition that involve a series of tasks over which task difficulty increases (Baddeley, 2003). We designed ordinal trend analysis (OrT) to identify activation patterns that increase monotonically in their expression as the experimental task parameter increases, while the correlative relationships between brain regions remain constant. Of specific interest are patterns that express positive ordinal trends on a subject-by-subject basis. A unique feature of OrT is that it recovers information about functional connectivity based solely on experimental design variables. In particular, there is no requirement by OrT to provide either a quantitative model of the uncertain relationship between functional brain circuitry and subject variables (e.g., task performance and IQ) or partial information about the regions that are functionally connected. In this letter, we provide a step-by-step recipe of the computations performed in the new OrT analysis, including a description of the inferential statistical methods applied. Second, we describe applications of OrT to an event-related fMRI study of verbal working memory and H(2)15O-PET study of visuo-motor learning. In sum, OrT has potential applications to not only studies of young adults and their cognitive abilities, but also studies of normal aging and neurological and psychiatric disease.

Adult↗
PubMed2005

Randomized, double-blind, placebo-controlled trial of fluoxetine treatment for elderly patients with dysthymic disorder.

OBJECTIVE: The authors compared the efficacy and side effects of fluoxetine and placebo in elderly outpatients with dysthymic disorder. METHODS: Patients were randomly assigned to fluoxetine (20 mg-60 mg/day) or placebo for 12 weeks in a double-blind trial. RESULTS: Of 90 randomized patients, 71 completed the trial. In the intent-to-treat sample, random regression analyses of the Hamilton Rating Scale for Depression (Ham-D; 24-item) and Cornell Dysthymia Rating Scale (CDRS) scores at each visit produced significant time x treatment group interactions favoring the fluoxetine group. Analysis of percentage change in Ham-D scores yielded no effect for treatment group, but a similar analysis of percentage change in CDRS scores yielded a main effect for treatment group, favoring fluoxetine over placebo. In the intent-to-treat sample, response rates were 27.3% for fluoxetine and 19.6% for placebo. In the completer sample, response rates were 37.5% for fluoxetine and 23.1% for placebo. CONCLUSION: Fluoxetine had limited efficacy in elderly dysthymic patients. The clinical features of elderly dysthymic patients are typically distinct from those of dysthymic disorder in young adults, and the findings suggest that treatments effective for young adult dysthymic patients may not be as useful in elderly dysthymic patients. Further research is needed to identify efficacious treatments for elderly patients with dysthymic disorder, and investigative tools such as electronic/computerized brain scans and neuropsychological testing may help identify the factors that moderate antidepressant treatment response and resistance.

Age Factors↗