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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
PubMed1999

Amphetamine disrupts P50 suppression in normal subjects.

BACKGROUND: P50 suppression is viewed as an operational measure of sensory "gating" that is reduced in patients with schizophrenia and their family members. Previous reports have demonstrated that neural gating is regulated by monoaminergic tone in rodent models of P50 suppression. METHODS: In this study, 11 healthy subjects participated in P50 event-related potential recordings at baseline and after either oral administration of dextroamphetamine (.3 mg/kg) or placebo, to determine if the administration of a monoaminergic agonist produces P50 suppression deficits similar to those observed in patients with schizophrenia. RESULTS: As hypothesized, amphetamine disrupted the suppression of the P50 event-related potential. There was a statistically significant decrement in P50 suppression during the amphetamine challenge condition (t10 = 3.15, p < .01, mean difference = -44.1%, d = -2.5) relative to the baseline P50 condition. A comparison of P50 suppression in the placebo and amphetamine conditions (both after a baseline recording session) revealed a significant amphetamine-induced disruption of P50 suppression (t6 = 3.71, p < .01, mean difference = -54.4%, d = -3.14). CONCLUSIONS: The biochemical alterations associated with an amphetamine-induced disruption of P50 suppression in this study may be related to the pathophysiology of P50 suppression deficits in schizophrenia. The findings are consistent with several careful examinations of suppression deficits in rodent models that have identified the monoaminergic regulation of P50 suppression. These data indicate that amphetamine induces a disruption of P50 suppression in normal subjects.

Adrenergic Agents↗
PubMed1999

Transcranial magnetic stimulation: applications in neuropsychiatry.

In the 1990s, it is difficult to open a newspaper or watch television and not find someone claiming that magnets promote healing. Rarely do these claims stem from double-blind, peer-reviewed studies, making it difficult to separate the wheat from the chaff. The current fads resemble those at the end of the last century, when many were falsely touting the benefits of direct electrical and weak magnetic stimulation. Yet in the midst of this popular interest in magnetic therapy, a new neuroscience field has developed that uses powerful magnetic fields to alter brain activity--transcranial magnetic stimulation. This review examines the basic principles underlying transcranial magnetic stimulation, and describes how it differs from electrical stimulation or other uses of magnets. Initial studies in this field are critically summarized, particularly as they pertain to the pathophysiology and treatment of neuropsychiatric disorders. Transcranial magnetic stimulation is a promising new research and, perhaps, therapeutic tool, but more work remains before it can be fully integrated in psychiatry's diagnostic and therapeutic armamentarium.

Animals↗
PubMed1999

Serotonin, cerebral blood flow, and cerebral metabolic rate in geriatric major depression and normal aging.

While there is substantial evidence for abnormalities in serotonin (5-HT) neurotransmission in major depressive disorder (MDD), almost all of the findings derive from studies of young adults. Moreover, relatively little research has assessed brain 5-HT transmission in vivo. Neuroendocrine studies do not permit evaluation of a range of brain regions, but only the limited circuitry associated with hormone release. Data from autopsy studies are limited by the difficulties of assessment of the acute clinical picture before death, and by post-mortem artifacts. In vivo neuroimaging techniques overcome many of the methodological limitations of both these approaches. There is a large body of imaging data indicating regional cerebral blood flow (rCBF) and cerebral metabolic rate (rCMR) decrements both with aging and in patients with MDD. While the physiological bases for these phenomena are largely unknown, changes in brain 5-HT function may be involved. Neuroanatomical studies have revealed an intricate network of 5-HT-containing neurons within the cerebral microvasculature, with physiological evidence for serotonergic control of both rCBF and rCMR. Acute pharmacological challenges are available to probe brain 5-HT function. Such paradigms, using neuroendocrine responses as endpoints, have been of some utility in predicting outcome with antidepressant treatment. The role of 5-HT dysregulation in geriatric MDD takes on more importance given concerns regarding putative reduced efficacy of serotonin-specific reuptake inhibitors (SSRIs) in this population. If this is due to diminished responsivity of 5-HT systems, then the ability to identify antidepressant nonresponders via 5-HT challenge in combination with neuroimaging measures may have important clinical utility.

Aged↗
PubMed1999

Naloxone in the prevention of the adverse cognitive effects of ECT: a within-subject, placebo controlled study.

Electroconvulsive therapy (ECT) is a highly effective treatment for major depression, but is also associated with characteristic cognitive side effects. Several reports document that endogenous opioids and their receptors are activated by electroconvulsive shock (ECS) and that naloxone in doses sufficient to block endogenous opioid receptors may reverse ECS-induced retrograde amnesia. This placebo-controlled, randomized, within-patient study was conducted to examine the potential of naloxone, given in doses sufficient to block opioid receptors (high dose), to ameliorate acute anterograde and retrograde memory impairments following ECT. Compared to placebo and low dose naloxone, high dose naloxone administered immediately before ECT resulted in significant reductions in anterograde amnesia, and better performance on an attention task. Both low and high dose naloxone improved verbal fluency. There were no beneficial effects of high dose naloxone on retrograde amnesia, and an indication that high dose naloxone may have worsened retrograde amnesia for shape stimuli. There were no effects of high dose naloxone on seizure duration, vital signs, and subjective side effects. The study is consistent with prior research in which change in behavioral and physiological measures was produced principally by naloxone doses sufficient to block endogenous opioid receptors and offers evidence of the potential for ameliorating some adverse cognitive effects associated with ECT.

Adult↗
PubMed1999

Inadequacy of antidepressant treatment for patients with major depression who are at risk for suicidal behavior.

OBJECTIVE: The authors' goal was to determine whether suicide attempters with major depression received more intensive antidepressant treatment than depressed patients who had not attempted suicide. METHOD: One hundred eighty inpatients who met DSM-III-R criteria for a major depressive episode according to the Structured Clinical Interview for DSM-III-R were enrolled in the study. All patients were assessed for lifetime history of suicide attempts. Depressive symptoms at the index hospitalization were assessed with the Hamilton Depression Rating Scale and the Beck Depression Inventory. Strength of antidepressant treatment over the 90 days preceding the hospitalization was scored by using the Antidepressant Treatment History Form. RESULTS: A large majority of the depressed patients with a history of suicide attempts, who were at higher risk for future suicide and suicide attempts, received inadequate treatment. Similarly, most of the depressed patients at lower risk for suicide attempts also received inadequate treatment. CONCLUSIONS: Major depression is undertreated pharmacologically, regardless of history of suicide attempt. Some suicide attempts may be preventable if the problem of underdiagnosis and undertreatment of depression can be overcome by psychoeducation for health professionals and the public.

Adult↗
PubMed1999

Electroconvulsive therapy and suicide risk.

For major psychiatric disorders in which suicidality is often a symptom, electroconvulsive therapy (ECT) is an established, highly effective treatment. In fact, suicidal risk may be an indication for the use of ECT to treat those disorders. The authors present new data and review clinical experience that indicate that ECT often exerts a profound short-term beneficial effect on suicidality. Little, if any, evidence supports a long-term positive effect of ECT on suicide rates, especially if diagnostically heterogeneous groups are considered. However, patients may have been assigned ECT precisely because they were suicidal and, hence, these reports may represent underestimates. As a whole, the published reports are weakened by methodological shortcomings, such as lack of controls, weak design, and possible cohort effects. In fact, most studies were designed to examine the impact of ECT on mortality rates in general, and all but one study found reductions in overall mortality, the source of which remains undetermined.

Antipsychotic Agents↗
PubMed1999

The anticonvulsant hypothesis of the mechanisms of action of ECT: current status.

Electroconvulsive therapy exerts a variety of anticonvulsant effects. The linkage between specific anticonvulsant effects and the efficacy of ECT is examined in relation to changes in seizure threshold, seizure duration, and seizure expression, and alterations in cerebral blood flow (CBF) and metabolism, and in EEG slow-wave activity. New findings are presented that the magnitude of the change in seizure threshold over the ECT course is associated with therapeutic outcome, particularly with right unilateral (RUL) ECT. New findings also indicate that the change in seizure threshold covaries with the magnitude of global reductions in CBF over the treatment course, is inversely related to some inhibitory aspects of seizure expression, and is independent of the cumulative decrease in seizure duration. Considerable evidence has accrued associating the anticonvulsant and antidepressant effects of ECT. However, critical experiments should be conducted in which the effects of augmenting and blocking anticonvulsant actions are studied in relation to efficacy.

Anticonvulsants↗
PubMed1999

The Texas Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Major Depressive Disorder.

BACKGROUND: This article describes the development of consensus medication algorithms for the treatment of patients with major depressive disorder in the Texas public mental health system. To the best of our knowledge, the Texas Medication Algorithm Project (TMAP) is the first attempt to develop and prospectively evaluate consensus-based medication algorithms for the treatment of individuals with severe and persistent mental illnesses. The goals of the algorithm project are to increase the consistency of appropriate treatment of major depressive disorder and to improve clinical outcomes of patients with the disorder. METHOD: A consensus conference composed of academic clinicians and researchers, practicing clinicians, administrators, consumers, and families was convened to develop evidence-based consensus algorithms for the pharmacotherapy of major depressive disorder in the Texas mental health system. After a series of presentations and panel discussions, the consensus panel met and drafted the algorithms. RESULTS: The panel consensually agreed on algorithms developed for both nonpsychotic and psychotic depression. The algorithms consist of systematic strategies to define appropriate treatment interventions and tactics to assure optimal implementation of the strategies. Subsequent to the consensus process, the algorithms were further modified and expanded iteratively to facilitate implementation on a local basis. CONCLUSION: These algorithms serve as the initial foundation for the development and implementation of medication treatment algorithms for patients treated in public mental health systems. Specific issues related to adaptation, implementation, feasibility testing, and evaluation of outcomes with the pharmacotherapeutic algorithms will be described in future articles.

Algorithms↗
PubMed1999

Continuation ECT in treatment-resistant schizophrenia: a controlled study.

In patients with treatment-resistant schizophrenia (TRS), this study compared the efficacy of continuation treatment with flupenthixol alone, continuation electroconvulsive therapy (ECT) alone, and combined continuation ECT and flupenthixol. One hundred fourteen TRS patients received acute treatment (Phase I) with bilateral ECT and flupenthixol (12-24 mg/day). Fifty-eight patients met remitter criteria, including clinical stability during a 3-week stabilization period, and were eligible for the continuation treatment study (Phase II). Fifty-one patients enrolled in the single-blind Phase II continuation trial, and were randomized to the three treatment groups. The duration of the Phase II study was 6 months. Assessments of outcome included the Brief Psychiatric Rating Scale, Global Assessment of Functioning, and the Mini-Mental State Examination. Forty-five patients either relapsed or completed the Phase II study, and six patients dropped out. Among completers, 6 of 15 (40%) patients relapsed in the combined continuation ECT and flupenthixol group. In both the group treated with continuation ECT alone and that with flupenthixol alone, 14 of 15 (93%) patients relapsed. Analyses of intent-to-treat and completer samples demonstrated a marked advantage for the combination treatment condition in relapse prevention. Furthermore, all eight patients who received maintenance ECT combined with neuroleptic medication (Phase III study) maintained therapeutic benefits during the follow-up period of 3-17 months after the continuation treatment study. Among TRS patients who respond to acute combination treatment with ECT and neuroleptic therapy, continuation of this combination treatment is more effective in relapse prevention than use of ECT or neuroleptic therapy alone.

Adult↗
PubMed1998

Effects of electroconvulsive therapy on plasma vasopressin and oxytocin.

BACKGROUND: Animal studies suggest that vasopressin has cognitive-enhancing properties and oxytocin may have amnestic effects. A clinical report suggests that the acute increase in oxytocin-associated neurophysin predicts clinical response to electroconvulsive therapy (ECT) in depressed patients. METHODS: Medication-free patients with major depression were randomized to receive right unilateral or bilateral ECT administered with electrical stimulus intensity at either just above seizure threshold or at 150% above seizure threshold. The associations between plasma vasopressin, oxytocin, ECT treatment parameters, clinical outcome, and cognitive effects were assessed. RESULTS: The sample comprised 55 patients. At the second ECT, patients receiving ECT at 150% above initial seizure threshold had significantly greater increases in plasma vasopressin than patients receiving low-dose ECT (ps < .01-.04), with no effects of electrode placement. At the second and ninth ECT treatments, the vasopressin or oxytocin surges were not associated with clinical improvement, seizure duration, time to orientation, or memory test performance. There were inverse trend-level associations between the acute surge in oxytocin levels at the ninth ECT and clinical response, contradicting a report in the literature. CONCLUSIONS: Overall, these findings do not support the hypothesis that diencephalic seizure propagation is central to the mechanism of action of ECT.

Cognition↗
PubMed1998

Prolactin response to electroconvulsive therapy: effects of electrode placement and stimulus dosage.

BACKGROUND: It is unclear whether the serum prolactin (PRL) surge following electroconvulsive therapy (ECT) is a marker of optimal ECT administration. We investigated the relations among PRL surge, stimulus parameters, and outcome in major depressive disorder (MDD). METHODS: Seventy-nine patients with MDD were randomized in a double-blind trial to right unilateral (RUL) or bilateral (BL), and to low-dose (just above seizure threshold) or high-dose (2.5 x threshold) ECT. RESULTS: Change in PRL (delta PRL) varied among treatment groups, with significant effects of electrode placement (BL > RUL, p < .006), electrical dosage (high > low, p < .04), and gender (female > male, p < .005). There was no evidence that clinical improvement was associated with greater PRL surge. CONCLUSIONS: Although delta PRL varied with parameters impacting on response rates, these data indicate the PRL surge cannot serve as a useful index of clinically effective treatment. This finding does not support the view that diencephalic seizure propagation is necessary for ECT to exert therapeutic effects.

Adult↗
PubMed1998

Use of ECT for the inpatient treatment of recurrent major depression.

OBJECTIVE: The authors' goals were to determine the frequency and distribution of ECT for general hospital inpatients with recurrent major depression and to estimate the effects of prompt ECT on the length and cost of inpatient care. METHOD: Data from the 1993 Healthcare Cost and Utilization Project were analyzed to determine the rate of ECT use for adult inpatients with a principal discharge diagnosis of major depression, recurrent. Associations between prompt initial use of ECT (in the first 5 hospital days) and length and cost of inpatient care were examined before and after control for sociodemographic, diagnostic, and hospital organizational characteristics. RESULTS: An estimated 9.4% of general hospital adult inpatients with a principal diagnosis of recurrent major depression received ECT in the survey year. A majority (59.2%) of these received their initial ECT session within the first 5 days after hospital admission. In univariate analyses, the likelihood of receiving ECT was greater for older patients, whites, privately insured individuals, and patients who lived in more affluent areas. Patients who received ECT tended to have relatively long and costly admissions. After control for several demographic, diagnostic, and hospital organizational characteristics, prompt ECT (as compared with delayed ECT or none) was associated with significantly shorter and less costly inpatient care. CONCLUSIONS: The longer stays and higher treatment costs associated with ECT may be a consequence of patient selection. When patient selection is taken into account, prompt administration of ECT is associated with shorter and less costly hospital stays. Nonetheless, economically disadvantaged patients are relatively unlikely to receive this treatment.

Adolescent↗
PubMed1998

A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease.

OBJECTIVE: The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. METHOD: In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg/day (standard dose), and haloperidol, 0.50-0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol. RESULTS: For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. CONCLUSIONS: The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors.

Aged↗
PubMed1998

The relative efficiency of altering pulse frequency or train duration when determining seizure threshold.

In 12 depressed inpatients referred for bilateral electroconvulsive therapy (ECT), each patient was titrated at the first treatment session by using an ascending method-of-limits procedure with a step-wise increase in pulse frequency (frequency titration) or train duration (duration titration). At the second treatment session, seizure threshold was redetermined by using the method (frequency or duration titration) not used at the first treatment. Frequency or duration was maintained at the lowest level when the other parameter was titrated. Seizure threshold was significantly lower with duration titration (mean, 90 mC; SD, 27.3) than frequency titration (mean, 114 mC; SD, 35.6; p = 0.03). On average, patients in the duration-titration group required 1.2 (SD, 0.6) subconvulsive stimulations before a seizure was elicited, and patients in the frequency-titration group required 1.7 (SD, 0.9) subconvulsive stimulations before a seizure was elicited, a nonsignificant difference. These findings suggest that to elicit a seizure during ECT, increasing train duration may be slightly more efficient than increasing frequency. Basic and other clinical research findings indicate that increasing pulse width may be an inefficient way to elicit a seizure. Therefore the following sequence in the determination of seizure threshold is worth considering when using dose-titration or related techniques: the train duration should be increased first before increasing pulse frequency, and the decision to increase pulse width should be reserved for patients who do not seize at the maximal duration and frequency settings. Further empiric research is needed to establish the utility of this approach.

Adult↗
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↗