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Biomedical subjects

G S Leverich

Publications and source records attributed to G S Leverich.

42 records · Page 3Linked to original sources

Carbamazepine prophylaxis in refractory affective disorders: a focus on long-term follow-up.

Twenty-four patients with refractory affective disorders who were taking carbamazepine were followed in an open-label fashion for an average of 4 years. Carbamazepine, usually in combination with lithium and other previously ineffective medications, reduced the number and severity of manic and depressive episodes. An overall illness index of morbidity (duration x severity) decreased 72% in the first year and 66% in the second year of carbamazepine treatment. One-half of the patients (N = 11) who were followed for more than 2 years showed a pattern of continued improvement (stable); the other half showed loss of prophylaxis (escape). Those showing the escape pattern had a more rapidly deteriorating course of illness in the 4 years before the study than those showing the stable improvement. Clinical and mechanistic implications of these findings are discussed, including the phenomenon of contingent tolerance as a possible explanation for the emergence of loss of efficacy in a subgroup of patients.

Adult↗

Suicide and course of illness in major affective disorder.

The relationship between a history of attempted suicide and prior course of illness was explored in 87 patients with major affective disorder. Fifty-eight percent of bipolar (n = 67) and 50% of unipolar (n = 20) patients had a history of a suicide attempt. Females were more likely to have made an attempt (67%) than males (42%) and were equally likely to have made a violent attempt. Course of illness and prior history of psychosis were similar in patients with and without a history of an attempt. However, in patients who made an attempt, the severity of the worst attempt was positively correlated with the duration of illness. Greater numbers of prior attempts were associated with greater lethality of the worst attempt. Suicidal ideation for the period of most severe depression in the prior 12 months did not correlate with any measure of lethality of suicide attempt. These data not only suggest the need for further studies of suicide in relationship to the longitudinal course of affective illness, but also the need for continuous reappraisal of suicidal risk in patients with recurrent affective disorders.

Adult↗

Preliminary evidence of the reliability and validity of the prospective life-chart methodology (LCM-p).

This article describes the use of the NIMH prospective life-charting methodology (NIMH LCM-p) in the context of a formal double-blind, clinical trial and provides preliminary evidence of its reliability and validity. Subjects included in this report were 30 outpatients with bipolar I and II disorder who completed the first 2 years of a long-term maintenance study: 1 year on carbamazepine or lithium and a crossover to the other in the second year. The LCM-p follows the same types of guidelines and principles utilized in the previously described retrospective life-chart process, allowing for continuity of illness assessment prior and subsequent to study entry. In the LCM-p, daily ratings of severity of mood symptoms based on the degree of associated functional incapacity, provide a more detailed topography of manic and depressive fluctuations. Inter-rater reliability was examined by comparing the severity of daily LCM-p ratings assigned by two raters. In order to assess the validity, we correlated the LCM-p ratings with well-standardized scales, including Hamilton and Beck Depression Ratings, Young Mania Ratings and the Global Assessment Scale (GAS). The Kappa scores for inter-rater reliability demonstrated significant and satisfactory strength of agreement with no fall off over 14 days prior to the rating interview. Strong correlations were found: (1) between the LCM-p average severity for depression rating and the mean Hamilton Depression Rating (r = 0.86, p < .001), and the Beck Depression Inventory (r = 0.73, p < .001); 2) between the LCM-p average severity for mania rating and the Young Mania Rating Scale (r = 0.61, p < .001); and (3) between the LCM-p average severity and the GAS (r = -0.81, p < .001). These preliminary data suggest the reliability and validity of the NIMH-LCM-p in assessing manic and depressive episode severity. It also provides a useful continuous daily measure of affective illness-related symptom fluctuations that allows for detailed prospective assessment of frequency and pattern of illness, treatment response, and continuity with retrospective life chart assessments.

Anticonvulsants↗

Neuroleptic exposure in bipolar outpatients in a research setting.

The study purpose was to determine the extent of neuroleptic exposure in bipolar outpatients maintained on mood-stabilizing medications and any clinical correlates associated with this exposure. Data on medication and severity of illness were gathered from the records (prospective and retrospective) of 70 bipolar patients involved in outpatient research studies at the National Institute of Mental Health (NIMH). The percentage of patients requiring neuroleptic treatment, percentage of time on neuroleptics during the period of observation, total dose of neuroleptics in chlorpromazine (CPZ) equivalency, and number of neuroleptic trials were among the variables calculated. Regression analyses and analyses of variance (ANOVAs) were performed to assess the relationships between neuroleptic exposure and clinical course. Forty-five patients (64.3%) had a neuroleptic trial during the prospective study. Subjects exposed to neuroleptics spent, on average, 15.4% (median, 6.0%) of the time in study on neuroleptic treatment, and were administered, on average, a total of 11,770.5 mg (median, 1,621.9 mg) of neuroleptics (in CPZ equivalency) per year in the prospective study. As expected, bipolar I compared with bipolar II patients had significantly higher neuroleptic exposure by a number of measures. The number of hospitalizations for mania prior to study entry was associated with greater prospective neuroleptic use during the study. Despite maintenance treatment with one or more moodstabilizing agents, we found a relatively high need for adjunctive neuroleptic medication even in this sample of high-functioning bipolar outpatients. These results highlight the need for the study of alternatives, as well as more effective primary mood-stabilizing agents.

Adult↗

Relationship between prior course of illness and neuroanatomic structures in bipolar disorder: a preliminary study.

OBJECTIVE: In this preliminary study, we examined the relationships between prior course and severity of illness and size of the hippocampus, temporal lobes, and third and lateral ventricles in patients with bipolar disorder. BACKGROUND: The few studies that have investigated relationships between course of illness measures and neuroanatomic structures in patients with bipolar disorder found divergent results. METHOD: Twenty-six outpatients, who met Diagnostic and Statistical Manual, Third Edition - Revised (DSM-III-R) criteria for bipolar disorder, received a magnetic resonance imaging (MRI) scan, from which volumes of the temporal lobes, hippocampi, third ventricle, and areas of the lateral ventricles were calculated. Prior course of illness variables were determined using the NIMH Life-Chart Method and were correlated to the volumetric measures of neuroanatomic structures using multiple regression analyses. RESULTS: A longer duration of illness was paradoxically associated with a larger left temporal lobe volume whether patients with a history of substance abuse were removed from the analyses. CONCLUSIONS: Additional studies are needed to both replicate and further examine the association of prior course of illness and larger hippocampal and ventricular volumes in bipolar disorder.

Adult↗

The efficacy and use of anticonvulsants in mood disorders.

Carbamazepine and valproate have utility in the acute and prophylactic treatment of mood disorders that appears comparable with that of lithium, but there are emerging differences as well, including responsiveness in some lithium-nonresponsive illness subtypes. Carbamazepine and valproate are generally well tolerated, but each has its own adverse effect profile and proclivity for pharmacokinetic interactions. The high potency (anticonvulsant) benzodiazepines have utility in mood disorders as adjuncts to mood stabilizers and often can obviate the need for neuroleptics. Several small studies suggest that the dihydropyridine L-type calcium channel blockers can be useful mood stabilizers, and several new antiepileptic agents, especially lamotrigine and gabapentin, may have mood-stabilizing properties. The actions of electroconvulsive therapy as they relate to activation of endogenous anticonvulsant processes, and the potential therapeutic effects of nonconvulsive repeated transcranial magnetic stimulation of brain, are promising areas of mood disorder research.

Anticonvulsants↗