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Biomedical subjects

H A Sackeim

Publications and source records attributed to H A Sackeim.

At least 19 recordsLinked to original sources
PubMed2001

Strengthening clinical effectiveness trials: equipoise-stratified randomization.

As psychiatric practice patterns evolve to take advantage of the growing list of treatments with proven efficacy, research studies with broader aims will become increasingly important. Randomized trials may need to accommodate multiple treatment options. In completely randomized designs, patients are assigned at random to one of the options, requiring that patients and clinicians find each of the options acceptable. In "clinician's choice" designs, patients are randomized to a small number of broad strategies and the choice of specific option within the broad strategy is left up to the clinician. The clinician's choice design permits some scope to patient and clinician preferences, but sacrifices the ability to make randomization-based comparisons of specific options. We describe a new approach, which we call the "equipoise stratified" design, that merges the advantages and avoids the disadvantages of the other two designs for clinical trials. The three designs are contrasted, using the National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression trial as an example.

Antidepressive Agents↗
PubMed2001

Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial.

CONTEXT: Electroconvulsive therapy (ECT) is highly effective for treatment of major depression, but naturalistic studies show a high rate of relapse after discontinuation of ECT. OBJECTIVE: To determine the efficacy of continuation pharmacotherapy with nortriptyline hydrochloride or combination nortriptyline and lithium carbonate in preventing post-ECT relapse. DESIGN: Randomized, double-blind, placebo-controlled trial conducted from 1993 to 1998, stratified by medication resistance or presence of psychotic depression in the index episode. SETTING: Two university-based hospitals and 1 private psychiatric hospital. PATIENTS: Of 290 patients with unipolar major depression recruited through clinical referral who completed an open ECT treatment phase, 159 patients met remitter criteria; 84 remitting patients were eligible and agreed to participate in the continuation study. INTERVENTIONS: Patients were randomly assigned to receive continuation treatment for 24 weeks with placebo (n = 29), nortriptyline (target steady-state level, 75-125 ng/mL) (n = 27), or combination nortriptyline and lithium (target steady-state level, 0.5-0.9 mEq/L) (n = 28). MAIN OUTCOME MEASURE: Relapse of major depressive episode, compared among the 3 continuation groups. RESULTS: Nortriptyline-lithium combination therapy had a marked advantage in time to relapse, superior to both placebo and nortriptyline alone. Over the 24-week trial, the relapse rate for placebo was 84% (95% confidence interval [CI], 70%-99%); for nortriptyline, 60% (95% CI, 41%-79%); and for nortriptyline-lithium, 39% (95% CI, 19%-59%). All but 1 instance of relapse with nortriptyline-lithium occurred within 5 weeks of ECT termination, while relapse continued throughout treatment with placebo or nortriptyline alone. Medication-resistant patients, female patients, and those with more severe depressive symptoms following ECT had more rapid relapse. CONCLUSIONS: Our study indicates that without active treatment, virtually all remitted patients relapse within 6 months of stopping ECT. Monotherapy with nortriptyline has limited efficacy. The combination of nortriptyline and lithium is more effective, but the relapse rate is still high, particularly during the first month of continuation therapy.

Antidepressive Agents↗
PubMed2001

Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials.

Testing the therapeutic potential of transcranial magnetic stimulation (TMS) in controlled trials requires a valid sham condition. Sham TMS is typically administered by tilting the coil 45--90 degrees off the scalp, with one or two wings of the coil touching the scalp. Lack of cortical effects has not been verified. We compared sham manipulations in their thresholds for eliciting motor-evoked potentials (MEPs) in human volunteers and in intracerebral measurements of voltage induced in the prefrontal cortex of a rhesus monkey. Three types of sham (one-wing 45 degrees and 90 degrees and two-wing 90 degrees tilt) induced much lower voltage in the brain than active TMS (67--73% reductions). However, the two-wing 45 degrees sham induced values just 24% below active TMS. This sham was about half as potent in inducing MEPs over the motor cortex as active TMS. Some sham TMS conditions produce substantial cortical stimulation, making it critical to carefully select the sham manipulation for clinical trials.

Adult↗
PubMed2001

Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome.

This open pilot study of vagus nerve stimulation (VNS) in 60 patients with treatment-resistant major depressive episodes (MDEs) aimed to: 1) define the response rate; 2) determine the profile of side effects; and, most importantly; 3) establish predictors of clinical outcome. Participants were outpatients with nonatypical, nonpsychotic, major depressive or bipolar disorder who had not responded to at least two medication trials from different antidepressant classes in the current MDE. While on stable medication regimens, the patients completed a baseline period followed by device implantation. A 2-week, single blind, recovery period (no stimulation) was followed by 10 weeks of VNS. Of 59 completers (one patient improved during the recovery period), the response rate was 30.5% for the primary HRSD(28) measure, 34.0% for the Montgomery-Asberg Depression Rating Scale (MADRAS), and 37.3% for the Clinical Global Impression-Improvement Score (CGI-I of 1 or 2). The most common side effect was voice alteration or hoarseness, 55.0% (33/60), which was generally mild and related to output current intensity. History of treatment resistance was predictive of VNS outcome. Patients who had never received ECT (lifetime) were 3.9 times more likely to respond. Of the 13 patients who had not responded to more than seven adequate antidepressant trials in the current MDE, none responded, compared to 39.1% of the remaining 46 patients (p =.0057). Thus, VNS appears to be most effective in patients with low to moderate, but not extreme, antidepressant resistance. Evidence concerning VNS' long-term therapeutic benefits and tolerability will be critical in determining its role in treatment-resistant depression.

Adolescent↗
PubMed2001

Repetitive transcranial magnetic stimulation to SMA worsens complex movements in Parkinson's disease.

OBJECTIVES: To evaluate the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) for Parkinson's disease (PD) by delivering stimulation at higher intensity and frequency over longer time than in previous research. Promising beneficial effects on movement during or after rTMS have been reported. METHODS: Ten patients with idiopathic PD were enrolled in a randomized crossover study comparing active versus sham rTMS to the supplementary motor area (SMA). Assessments included reaction and movement times (RT/MT), quantitative spiral analysis, timed motor performance tests, United Parkinson's Disease Rating Scale (UPDRS), patient self-report and guess as to stimulation condition. RESULTS: Two of 10 patients could not tolerate the protocol. Thirty to 45 min following stimulation, active rTMS as compared with sham stimulation worsened spiral drawing (P=0.001) and prolonged RT in the most affected limb (P=0.030). No other significant differences were detected. CONCLUSIONS: We sought clinically promising improvement in PD but found subclinical worsening of complex and preparatory movement following rTMS to SMA. These results raise safety concerns regarding the persistence of dysfunction induced by rTMS while supporting the value of rTMS as a research tool. Studies aimed at understanding basic mechanisms and timing of rTMS effects are needed.

Aged↗
PubMed2001

Electro-convulsive therapy practices in the community.

BACKGROUND: Controlled studies have demonstrated that variations in electro-convulsive therapy (ECT) technique impacts on efficacy and cognitive side effects. However, there is little information on the extent of variation in how ECT is practiced in community settings in the United States. METHODS: A survey of practice patterns was conducted at ECT facilities in the greater New York City metropolitan area. RESULTS: The 59 facilities varied considerably in many aspects of ECT practice, often clearly departing from the standards in the field. The more intensive the form of ECT used at facilities, the less likely was cognitive status assessed following the treatment course. CONCLUSION: There is marked variability in the nature of ECT practices in community settings. The extent to which this variability impacts on the benefits and risks of ECT needs to be examined.

Adolescent↗
PubMed2001

ECT in bipolar and unipolar depression: differences in speed of response.

OBJECTIVES: There is sparse evidence for differences in response to electroconvulsive therapy (ECT) between patients with bipolar or unipolar major depression, with virtually no information on speed of response. We contrasted a large sample of bipolar (BP) and unipolar (UP) depressed patients in likelihood and rapidity of clinical improvement with ECT. METHODS: Over three double-blind treatment protocols, 228 patients met Research Diagnostic Criteria for UP (n = 162) or BP depression (n = 66). Other than lorazepam PRN (3 mg/day), patients were withdrawn from psychotropics prior to the ECT course and until after post-ECT assessments. Patients were randomized to ECT conditions that differed in electrode placement and stimulus intensity. Symptomatic change was evaluated at least twice weekly by a blinded evaluation team, which also determined treatment length. RESULTS: Patients with BP and UP depression did not differ in rates of response or remission following the ECT course, or in response to unilateral or bilateral ECT. Degree of improvement in Hamilton Rating Scale for Depression scores following completion of ECT was also comparable. However, BP patients received significantly fewer ECT treatments than UP patients, and this effect was especially marked among bipolar ECT responders. Both BP I and BP II patients showed especially rapid response to ECT. CONCLUSIONS: The BP/UP distinction had no predictive value in determining ECT outcome. In contrast, there was a large effect for BP patients to show more rapid clinical improvement and require fewer treatments than unipolar patients. The reasons for this difference are unknown, but could reflect a more rapid build up of anticonvulsant effects in BP patients.

Adult↗
PubMed2001

A unilateral, prolonged, nonconvulsive seizure in a patient treated with bilateral ECT.

We report on a case of a 45-year-old man in an episode of major depression with psychotic features treated with bilateral electroconvulsive therapy (ECT). At the eighth treatment, he manifested unilateral, prolonged, nonconvulsive seizure activity on the left side, which lasted 351 seconds longer than seizure activity on the right, and was terminated with intravenous diazepam. This is the first report of a unilateral prolonged seizure. Its occurrence following bilateral ECT was particularly noteworthy. This case also highlights the importance of two-channel EEG recording during ECT. Without two recording channels we doubt that this event would have been detected, perhaps resulting in nonconvulsive status epilepticus.

Cerebral Cortex↗
PubMed2001

Focal prefrontal seizures induced by bilateral ECT.

INTRODUCTION: It has been proposed that the greater efficacy of bilateral (BL) over right unilateral (RUL) electroconvulsive therapy (ECT) at low stimulus intensity is due to differences in site of seizure initiation. We hypothesized that focal prefrontal seizures are more common with BL than RUL administration. METHOD: Records were reviewed of the 1,007 ECT treatments of 84 consecutive patients randomized to RUL or BL electrode placement. RESULTS: Eight events were identified in which there was an electroencephalographic seizure without motor manifestation. All of these events occurred at titration sessions and with BL stimuli (p = 0.002). These events were more likely to occur later in the course of treatment. DISCUSSION: We suggest that BL ECT may induce focal seizures in prefrontal areas and that these seizures are more likely to occur later in the treatment course.

Adult↗
PubMed2001

ECT in the treatment of status epilepticus.

INTRODUCTION: Owing to its potent anticonvulsant actions, electroconvulsive therapy (ECT) has been proposed as an intervention for treatment-resistant seizure disorders. METHOD: We review the literature on the use of ECT in treatment-resistant epilepsy and status epilepticus (SE) and present a case of a patient who was in nonconvulsive SE for 26 days and then treated with ECT after all standard pharmacological strategies were exhausted. Because of skull defects, a novel electrode placement was used. RESULTS: Owing to massively elevated seizure threshold attributable to concomitant anticonvulsant medications, extraordinarily high electrical dosage was needed for ECT to elicit generalized seizures. Status was terminated after three successful ECT-induced seizures. However, the long-term functional outcome of the patient was poor. DISCUSSION: The role of ECT in the treatment algorithm for SE is discussed.

Adult↗
PubMed2001

Decreased regional brain metabolism after ect.

OBJECTIVE: The antidepressant action of ECT may be related to its anticonvulsant properties. Positron emission tomography (PET) studies of regional cerebral metabolic rate for glucose were used to test this hypothesis. METHOD: Ten patients with major depression were studied with PET before and approximately 5 days after a course of bilateral ECT. Statistical parametric mapping was used to identify regions of decreased cerebral glucose metabolism. RESULTS: Widespread regions of decreased regional cerebral glucose metabolism were identified after ECT, especially in the frontal and parietal cortex, anterior and posterior cingulate gyrus, and left temporal cortex. A region-of-interest analysis similarly indicated post-ECT reductions in regional cerebral glucose metabolism. CONCLUSIONS: ECT reduces neuronal activity in selected cortical regions, a potential anticonvulsant and antidepressant effect.

Brain↗
PubMed2001

Neuropsychological dysfunction in depressed suicide attempters.

OBJECTIVE: Neuropsychological deficits in the context of psychiatric disease may be associated with suicide risk. In this study, neuropsychological performance was compared among depressed patients with at least one prior suicide attempt of high lethality, depressed patients with low-lethality prior attempts, depressed patients with no prior suicide attempts, and nonpatients. METHOD: Fifty unmedicated patients in a major depressive episode (21 with no history of suicide attempts and 14 and 15 patients with previous attempts of low and high lethality, respectively) and 22 nonpatients were assessed. Groups were comparable in age, education, occupational level, and estimated premorbid intelligence. The neuropsychological battery produced scores within five composite domains: general intellectual functioning (current), motor functioning, attention, memory, and executive functioning. RESULTS: Patients whose prior suicide attempts were of high lethality performed significantly worse than all groups on tests of executive functioning and were the only group to perform significantly worse than nonpatients on tests of general intellectual functioning, attention, and memory. A discriminant function analysis revealed two prominent dimensions in the data: one that discriminated high-lethality suicide attempters from all other groups (primarily associated with performance on tests of executive functioning) and another that discriminated all depressed patient groups from nonpatients (associated with performance on measures of attention and memory). For the patients with high-lethality prior suicide attempts, deficits did not appear to reflect diffuse brain damage from past attempts, since the results of tests commonly affected by diffuse injury were not selectively impaired. CONCLUSIONS: Neuropsychological deficits in depressed patients with high-lethality prior suicide attempts suggest impairment of executive functioning beyond that typically found in major depression. This more extensive neuropsychological impairment in the context of depression may be a risk factor for severe suicide attempts.

Adult↗
PubMed2001

Vagus nerve stimulation in depression.

Ever since the introduction of chemical and electrical convulsive treatment for psychiatric disorders in the 1930s and 1940s, biological techniques have been used extensively in the amelioration of a variety of psychiatric disorders. Techniques of recent vintage have included transcranial magnetic stimulation, deep brain stimulation and vagus nerve stimulation (VNS). Since VNS attenuates seizures in animal models, the treatment was initially developed and approved by the FDA for treatment of drug-resistant partial-onset epilepsy. Additional data, including the known neuroanatomy of the vagus nerve, effects of VNS on monoamines and mood improvement in patients with epilepsy who were treated with VNS, provided a rationale for further investigation in patients with primary mood disorders. VNS has been administered acutely for 10 weeks to 60 patients with treatment-resistant depression. Longer-term follow-up data has been analysed for the first 30 patients. Response rates have been at least 30% in the acute study. Similar to findings in epilepsy and in contrast to the usual results of long-term medication trials, longer term data regarding symptomatic and functional outcomes of depressed patients receiving VNS continue to look promising. As opposed to electroconvulsive therapy, VNS is not associated with cognitive impairment. These results have led to approval of VNS for the treatment of resistant depression (unipolar or bipolar) in both Europe and Canada. Currently, a pivotal double-blind acute study is underway in the US.

Animals↗