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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
PubMed1997

Psychomotor symptoms of depression.

OBJECTIVE: The authors summarize current knowledge regarding the psychomotor symptoms of depression. METHOD: Findings from the objective quantification of psychomotor symptoms are reviewed, and methodological issues are considered. The contemporary empirical literature regarding the diagnostic, prognostic, and potential pathophysiologic significance of psychomotor symptoms is summarized. RESULTS: It has been repeatedly shown that depressed patients differ from normal and psychiatric comparison groups with regard to objectively quantified gross motor activity, body movements, speech, and motor reaction time. Course of illness, diurnal variation, medication status, sex, and age are associated with agitation and retardation and should be controlled when one is studying psychomotor symptoms. Psychomotor symptoms in depression may have unique significance. They have high discriminative validity, may be the only symptoms of depression that distinguish depression subtypes, and are predictive of good response to tricyclic antidepressants. Results of brain imaging and biochemical studies link depression and motor symptoms to abnormalities in the basal ganglia and basal ganglia/thalamo-cortical circuits. CONCLUSIONS: The investigation of psychomotor disturbance in depression is specifically consistent with neo-Kraepelinian standards for the study of psychiatric disorders. Our current knowledge of psychomotor symptoms is conceptually obscure, yet a large body of evidence specifies their manifestation and supports their significance. Identifying the incidence of abnormal motor behaviors in depressed patients and assessing the component processes that accompany and determine their manifestation may be important advances in the study of psychomotor symptoms in depression.

Antidepressive Agents, Tricyclic↗
PubMed1997

Low use of neuroleptic drugs in the treatment of psychotic major depression.

OBJECTIVE: The adequacy of pharmacologic treatment received by patients with psychotic major depression was evaluated. METHOD: The authors systematically assessed the pharmacotherapy received by 187 depressed patients before initiation of ECT and compared the medication trials of those with psychotic (N = 53) and nonpsychotic (N = 134) depression. RESULTS: Despite a median of four medication trials and median index episode duration of 20 weeks, only two (4%) of the patients with psychotic depression received at least one adequate pharmacotherapy trial. In contrast, 70 (52%) of the patients with nonpsychotic depression received at least one adequate trial. Twenty-five (47%) of the patients with psychotic depression received either no neuroleptic treatment (N = 11) or treatment for less than 3 weeks (N = 14). Only eight (15%) received a daily neuroleptic dose higher than 200 mg of chlorpromazine equivalents. CONCLUSIONS: These findings suggest that many patients with psychotic major depression referred for ECT receive inadequate pharmacotherapy because of either the absence or the inadequate use of neuroleptic medication.

Antidepressive Agents↗
PubMed1996

Subjective memory complaints prior to and following electroconvulsive therapy.

Using the Squire Subjective Memory Questionnaire (SSMQ), depressed patients rated their memory functioning prior to a course of brief pulse, electroconvulsive therapy (ECT) within the 1 week following the course and 2 months later. Normal controls made similar ratings at comparable intervals. Prior to ECT, patients reported poorer memory functioning than controls. There was marked improvements in the patients' self-reports shortly following ECT, and at 2-month follow-up SSMQ scores were generally comparable in patients and controls. At all time points, the severity of depressive symptoms was strongly associated with patients' reports of memory dysfunction. SSMQ subscales ("depression" and "ECT" items) were not differentially sensitive to effects of ECT or depression. Relations between ECT treatment parameters and changes in patients' self-evaluations only emerged after controlling for clinical state change. Shortly following ECT, there were no relations between SSMQ scores and objective measures of cognitive functioning. However, 2 months following ECT, there was a suggestion that greater retrograde amnesia for autobiographical memories was associated with self-rating of greater memory impairment.

Adult↗
PubMed1996

The effects of electroconvulsive therapy on quantitative electroencephalograms. Relationship to clinical outcome.

BACKGROUND: The efficacy of electroconvulsive therapy (ECT) is determined by stimulus electrical intensity and electrode placement. Three theories offer different accounts for why increasing the stimulus dosage of right unilateral ECT enhances antidepressant effects. This study examined the effects of ECT on interictal quantitative electroencephalograms (EEGs), contrasting these theories in their predictions regarding global, lateralized, and topographic changes in ECT-induced slow-wave activity. The time course of EEG changes and associations with efficacy were also determined. METHODS: Sixty-two inpatients with major depressive disorder were randomized to ECT conditions that differed in stimulus intensity (low vs high dosage) and electrode placement (right unilateral vs bilateral). Resting, eyes closed, 19-lead EEG recordings were obtained at pretreatment, following a single treatment, following an average of 7 treatments, during the week following the ECT course, and after a 2-month follow-up period. RESULTS: Electroconvulsive therapy produced a marked short-term increase in delta and theta power. At a 2-month follow-up, there were no significant alterations in any frequency band. The ECT treatment conditions differed markedly in efficacy. Global and lateralized EEG effects did not distinguish effective and ineffective forms of treatment. Effective forms of ECT resulted in increased delta power in prefrontal regions, and this change was associated with the magnitude of symptomatic improvement. CONCLUSION: The induction of slow-wave activity in prefrontal cortex is linked to the efficacy of ECT.

Delta Rhythm↗
PubMed1996

Convulsive therapy in schizophrenia?

Schizophrenia is a clinical syndrome of extraordinary importance and complexity. Its early identification is difficult, and our concepts of its main characteristics have undergone many changes in the past century. Electroconvulsive therapy (ECT) was introduced as a treatment for dementia praecox. The initial reports were salutary, and the treatment was widely applied until it was replaced by psychoactive drugs. ECT was reintroduced in the 1970s in the treatment of therapy-resistant disorders. The initial reviews argued that ECT was not applicable in patients with schizophrenia, a conclusion based mainly on experience with chronic forms of the disorder. This article assesses the role of ECT in schizophrenia today. We find it to be an effective treatment for psychosis. ECT is particularly applicable in patients with first-break episodes, especially those marked by excitement, overactivity, delusions, or delirium; in young patients, to avoid debilitating effects of chronic illness; and in patients with syndromes characterized by catatonia, positive symptoms of psychosis, or schizoaffective features.

Chronic Disease↗
PubMed1996

Resistance to antidepressant medications and short-term clinical response to ECT.

OBJECTIVE: Traditionally, it has been widely assumed that the likelihood of response to ECT is independent of the adequacy of previous treatment with antidepressant medications. However, recent research has raised the possibility that medication-resistant patients with depression have a poorer clinical ECT outcome than patients who have not failed previous adequate medication trials. METHOD: Medication resistance of 100 patients with primary, unipolar, nonpsychotic major depression was evaluated during the index episode with the Antidepressant Treatment History Form. Patients were recruited and treated with ECT at three sites; standardized ECT and clinical assessment procedures were used. Clinical outcome was assessed immediately and 1 week after completion of the ECT course. RESULTS: Patients who previously had failed one or more adequate antidepressant medication trials were less likely to respond to subsequent ECT than patients not known to be medication resistant. This finding held within each study site, whether clinical response was assessed categorically or in terms of the magnitude of symptomatic improvement and after the authors accounted for other potential predictors of clinical outcome. Resistance to heterocyclic antidepressants predicted poorer outcome after ECT, while resistance to selective serotonin reuptake inhibitors and monoamine oxidase inhibitors did not show significant predictive relations. CONCLUSIONS: While a substantial percentage of medication-resistant patients respond to ECT, clinical outcome in this group is inferior to that of patients without established medication resistance. The predictive power of medication resistance is generalizable across diverse clinical settings, particularly for heterocyclic antidepressants, which perhaps suggests an overlap in the mechanisms of actions of ECT and this medication class.

Aged↗
PubMed1996

Who responds to electroconvulsive therapy? A comparison of effective and ineffective forms of treatment.

BACKGROUND: It has been reported that real ECT is more effective than simulated treatment among depressed patients with delusions and/or retardation, and that ECT is not effective among depressed patients who lack these features. METHOD: In two randomised, double-blind studies, 143 patients with major depression were subtyped regarding psychosis, retardation and agitation. In both studies, low dosage, right unilateral ECT was ineffective compared with other forms of ECT. This report examined whether the depressive subtypes differed in clinical response to the ineffective and effective forms of ECT. RESULTS: The therapeutic advantage of effective forms of ECT was similar across the depression subtypes. Patients who lacked both psychosis and retardation showed this pattern. CONCLUSIONS: The findings cast doubt on the utility of these depression subtypes in predicting ECT response. ECT is a viable treatment option for patients with major depression regardless of the presence or absence of psychosis, retardation and/or agitation.

Adult↗
PubMed1996

Fluoxetine treatment of dysthymia in the elderly.

BACKGROUND: Despite their prevalence, little is known about the treatment of mild depressive syndromes in older patients. The purpose of this study was to evaluate the efficacy of fluoxetine in dysthymic disorder in the elderly. METHOD: Twenty-three elderly outpatients with dysthymic disorder (DSM-III-R criteria) entered a 13-week study of fluoxetine (2-week placebo run-in period and 11 weeks of fluoxetine treatment with a dose range of 20-60 mg/day). Ratings to assess clinical response included the Hamilton Rating Scale for Depression (HAM-D), the Clinic Global Impression (CGI), and the Cornell Dysthymia Rating Scale (CDRS). RESULTS: Nine patients (39%) had never received psychiatric treatment during the index episode, despite a long duration of illness (mean +/- SD = 18.5 +/- 17.1 years). Twenty of the 23 patients completed the entire study. The mean +/- SD HAM-D (24-item) score decreased from 14.6 +/- 3.7 to 7.9 +/- 5.0 during the trial, and the CDRS score decreased from 28.1 +/- 9.1 to 15.7 +/- 10.0. When response criteria of a 50% reduction from baseline in the HAM-D score, final HAM-D score < or = 8, and a CGI score of 1 or 2 (very much or much improved) were used, 12 (60%) of the completers were responders. Side effects were uncommon, and the fluoxetine was generally well tolerated. CONCLUSION: These preliminary findings suggest that fluoxetine is an effective treatment in elderly patients with dysthymic disorder. Double-blind, placebo-controlled studies are warranted.

Adult↗
PubMed1996

Exceptionally high seizure threshold: ECT device limitations.

Three patients had exceptionally high seizure threshold, as determined by an empirical titration procedure. Initial seizure threshold was 896 mC in two of the patients. The third patient had an initial threshold of 336 mC that increased to 840 mC at the end of the course of electroconvulsive therapy (ECT), and remained elevated during a second course of ECT. All three patients were elderly men with complicated medical histories and ongoing low-dose benzodiazepine use. Each patient had an excellent response to ECT delivered with a custom modified device, capable of delivering more than twice the charge of ECT devices presently commercially available in the United States. Implications for the administration of ECT in patients with exceptionally high seizure threshold and the limitations of current device output are discussed.

Aged↗
PubMed1995

Regional cerebral blood flow in mood disorders: IV. Comparison of mania and depression.

Cortical regional cerebral blood flow (rCBF) was assessed in minimally medicated, relatively young adults in episodes of either acute mania (n = 11) or major depression (n = 11) and in matched normal control subjects (n = 11), using the 133xenon inhalation method, under eyes-closed, resting conditions. The three groups were equivalent in global CBF. Both patient groups showed significant reductions of rCBF in anterior cortical areas and reduction of the normal anteroposterior gradient. In addition, there was evidence of abnormal, albeit similar, patterns of flow lateralization on a regional basis in both clinical groups compared with normal subjects. An exploratory analysis revealed preliminary evidence of rCBF differences between the clinical groups, localized to the inferior frontal cortex. Otherwise, the evidence in this study suggests that young adult manic and depressed patients are predominantly similar in cortical rCBF parameters.

Administration, Inhalation↗
PubMed1995

Predictors of retrograde amnesia following ECT.

OBJECTIVE: Substantial progress has been made in identifying how the treatment parameters used in ECT impact on cognitive side effects. However, there is limited information regarding individual differences in vulnerability to these side effects. The authors examined patients' pretreatment global cognitive status and postictal orientation recovery time as potential predictors of the magnitude of retrograde amnesia for autobiographical memories after ECT. METHOD: Seventy-one inpatients with major depressive disorder were randomly assigned to four ECT conditions that varied in electrode placement (right unilateral versus bilateral) and stimulus dosage (low versus high intensity). Orientation recovery time was assessed at virtually every session during the course of ECT. Global cognitive status was assessed with the modified Mini-Mental State examination before treatment, during the week after termination of treatment, and 2 months after treatment ended. Retrograde amnesia was assessed at these same time points with the Autobiographical Memory Interview. RESULTS: Pre-ECT global cognitive status and the duration of postictal disorientation were strong predictors of the magnitude of retrograde amnesia in the week after the course of ECT and at 2-month follow-up. In general, these relationships were maintained regardless of technical parameters in the administration of the ECT. CONCLUSIONS: Patients who manifest global cognitive impairment before treatment and patients who experience prolonged disorientation in the acute postictal period may be the most vulnerable to persistent retrograde amnesia for autobiographical information.

Amnesia, Retrograde↗
PubMed1995

Hearing loss and asymmetry in major depression.

To assess patterns of hearing loss and asymmetry in major depressive disorder (MDD), pure-tone and brief-click audiometric thresholds were measured in 59 inpatients with MDD and 40 normal control subjects. For both tasks, patients had higher bilateral thresholds, with marked hearing loss for the highest pure-tone frequency. At lower frequencies, patients displayed significant asymmetry, with poorer hearing in the left ear. After ECT, patients maintained the bilateral hearing losses; however, the baseline asymmetry resolved. These findings suggest that bilateral hearing loss may be a stable characteristic in severe depression. Poorer left ear pure-tone hearing may be present during the depressed state. The baseline asymmetry in audiometric deficits suggests right-hemisphere dysfunction in severe MDD.

Acoustic Stimulation↗
PubMed1995

Cortical perfusion and gray matter weight in frontal lobe dementia.

To evaluate the pathophysiology of frontal lobe dementia (FLD), the authors compared regional cerebral blood flow (rCBF) in matched groups of FLD, probable Alzheimer's disease (AD), and major depression patients and normal control subjects (n = 7 each). The planar xenon-133 technique allowed full quantification of cortical perfusion and estimates of the relative weight of gray matter (wg). FLD patients showed lower blood flow and wg in the frontal cortex than the other groups. Mean cortical perfusion was correlated with cortical wg in the FLD group only. These findings 1) suggest that matched reductions of frontal gray matter weight and perfusion occur in FLD and 2) support the use of rCBF in distinguishing FLD from AD and severe depression.

Aged↗
PubMed1995

Visual fixation and smooth pursuit eye movement abnormalities in patients with schizophrenia and their relatives.

Increasing evidence suggests that smooth pursuit eye movement (SPEM) dysfunction may serve as an endophenotype or genetic marker of schizophrenia. The authors tested SPEM and visual fixation (VF) in 31 patients with schizophrenia, 33 of their first-degree relatives, and 24 patients with major depressive disorder. A high rate of abnormal VF was found in schizophrenic patients and their first-degree relatives, but not in affective disorder patients with or without psychotic features. Rate of VF abnormality distinguished schizophrenic patients from acutely depressed mood disorder patients; SPEM did not. VF and SPEM performance correlated only moderately, suggesting that the pathophysiologies of these two eye movement abnormalities may be partially independent. Implications for identifying a schizophrenia endophenotype are discussed.

Adult↗
PubMed1995

Effects of electroconvulsive therapy on plasma GABA.

There are no published data on the effects of seizures on indices of gamma-aminobutyric acid (GABA) function in human subjects. In study 1, the effects of electroconvulsive therapy (ECT) on free plasma GABA were studied in 39 inpatients with major depressive disorder. Acutely after ECT, free plasma GABA was significantly reduced for up to 1 h after seizure termination, and this finding replicated strongly in a subgroup of six patients who received a second course of ECT. In a second study at a different site that compared sham ECT and real ECT in seven patients, some doubt was raised about the replicability of the acute effect of ECT on GABA levels. Nonetheless, the strength of the findings in the larger study 1 sample suggests that, unlike virtually all other biochemical indices, free plasma GABA may be reduced acutely after ECT. This acute decrease could reflect decreased levels of GABA in brain extracellular space or decreased brain turnover. In study 1, compared with ECT nonresponders, ECT responders had higher GABA levels at both baseline and after a course of ECT. Because plasma GABA levels are known to be low in a subset of patients with major depression, the higher GABA levels observed in clinical responders before and after the ECT course indirectly suggest that patients least abnormal in GABA levels may show superior clinical response. This also suggests that low plasma GABA is not a state marker for depression.

Adult↗
PubMed1995

Subjective side effects during electroconvulsive therapy.

In 92 depressed patients who were randomized to unilateral or bilateral electroconvulsive therapy (ECT) at either low dosage (just above seizure threshold) or high dosage (2.5 times the seizure threshold), subjective side effects were assessed with the Columbia ECT Subjective Side Effects Schedule. A research nurse administered the instrument 4 h after each treatment during the ECT course. In 41 patients, the instrument was also administered before the ECT course. Headache, disorientation, and memory complaints were the most common subjective side effects during the ECT course. Somatic side effects did not change from early to late in the ECT course, and were not influenced by ECT electrode placement or dosage. Most individual somatic side effects, including nausea, tiredness, and muscle aches/pains did not change from pre-ECT to during the ECT course, and may have been a function of the persistent somatic symptoms of depression. Cognitive complaints increased from pre-ECT to during the ECT course, but there was no overall change from pre-ECT to immediately after the ECT course. Cognitive complaints were greater with bilateral compared with unilateral ECT, with no significant effect of electrical dosage. During the ECT course, subjective mood improved and psychomotor agitation decreased, particularly in clinical responders. These findings suggest that most putative somatic side effects are related to the depressive state rather than being induced by ECT. The observed changes reinforce the need to evaluate both subjective and objective side effects during ECT.

Affect↗