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Biomedical subjects

M D Shelton

Publications and source records attributed to M D Shelton.

15 recordsLinked to original sources
PubMed2001

Current research on rapid cycling bipolar disorder and its treatment.

Rapid cycling is a pattern of presentation of bipolar disorder that specifies the course of the illness and is associated with a greater morbidity. The validity of rapid cycling as a distinct course modifier for bipolar disorder has been demonstrated and the term has been incorporated into the DSM-IV. The phenomenon of rapid cycling tends to appear late in the course of the disorder, occurs more frequently among females, and is more frequently seen in patients with bipolar type II disorder. Stimulants such as cocaine may also play some role in rapid-cycling. It is generally accepted that a recent history of rapid cycling predicts non-response to monotherapy with lithium and probably carbamazepine as well; however it is also possible that concurrent use of antidepressants may play a role in destabilizing the illness course under these agents. Thus, clinical considerations suggest that discontinuing antidepressants may facilitate the recovery process. Among clinically available monotherapies, valproate and lamotrigine appear to be the most useful clinically. However, other treatments such as lithium, carbamazepine, the atypical antipsychotic agents, thyroid hormone, and bupropion are frequently needed augmentation strategies. Electroconvulsive therapy may also prove efficacious in selected cases. The present paper provides a critical review of the evidence for the foregoing clinical issues in rapid cycling.

Acute Disease↗
PubMed2001

A pilot study of topiramate as monotherapy in the treatment of acute mania.

This small-scale pilot study was performed to grossly document safety and any evidence of efficacy of topiramate in bipolar disorder. Ten patients hospitalized for acute mania were given open-label topiramate monotherapy for up to 28 days. The mean Young Mania Rating Scale (YMRS) score decreased from 32 (range, 26-40) at baseline to 22 (range, 2-40) at the end of the study. Five patients exhibited evidence of moderate to marked improvement, three subjects had at least a 50% reduction in YMRS scores, and the other two patients experienced an improvement of 25% to 49% on the YMRS. The preliminary findings of this small series suggest that topiramate may be effective in acute mania. Double-blind controlled trials are now needed to further investigate the efficacy and safety of topiramate in bipolar disorder.

Adult↗
PubMed2001

Evolving methodologies in bipolar disorder maintenance research.

Background During the development of a new treatment for bipolar disorder, maintenance studies are used to evaluate the ability of the putative mood stabiliser to prevent relapse and recurrence of further episodes. Comparisons with the early bipolar disorder maintenance studies indicate that the methodologies of recent trials have evolved substantially. Aims To review the methods used in the first- and second-generation maintenance studies, highlighting the differences of the various designs. Method Literature review. Results Methods that have evolved the most include patient enrolment, randomisation schemes and the use of outcome measures and statistical analyses. In addition, regulatory and commercial issues have also influenced study design. Conclusion There is little consensus on the methodology of bipolar disorder maintenance studies. As the integration of newer therapies into routine clinical practice is dependent on the evidence from controlled studies, it is essential that future maintenance trials in bipolar disorder achieve adequate methodological rigour without sacrificing overall feasibility.

Journal Article↗
PubMed2001

Evolving methodologies in bipolar disorder maintenance research.

BACKGROUND: During the development of a new treatment for bipolar disorder, maintenance studies are used to evaluate the ability of the putative mood stabilizer to prevent relapse and recurrence of further episodes. Comparisons with the early bipolar disorder maintenance studies indicate that the methodologies of recent trials have evolved substantially. AIMS: To review the methods used in the first- and second-generation maintenance studies, highlighting the differences of the various designs. METHOD: Literature review. RESULTS: Methods that have evolved the most include patient enrollment, randomisation schemes and the use of outcome measures and statistical analyses. In addition, regulatory and commercial issues have also influenced study design. CONCLUSION: There is little consensus on the methodology of bipolar disorder maintenance studies. As the integration of newer therapies into routine clinical practice is dependent on the evidence from controlled studies, it is essential that future maintenance trials in bipolar disorder achieve adequate methodological rigour without sacrificing overall feasibility.

Antimanic Agents↗
PubMed2001

Bipolar rapid cycling: focus on depression as its hallmark.

The phenomenon of frequent cycling in bipolar disorder was first recognized by Emil Kraepelin in 1913. More recently, rapid cycling has been reported to be a predictor of nonresponse to treatment. At the time of presentation, most patients with DSM-IV-defined rapid cycling appear to be in the depressed phase of their illness. Frequent and more severe episodes of depression appear to be the hallmark of rapid cycling. Reported in this article are recent preliminary data suggesting that the combination of lithium and divalproex sodium administered continuously over 6 months appears to result in marked acute and continuation antimanic efficacy in 85% of patients and marked antidepressant efficacy in 60%. However, only one half of patients experienced bimodal stabilization. Comorbid alcohol, cannabis, and/or cocaine abuse and/or dependence did not appear to directly affect the spectrum of efficacy of lithium and divalproex or response rates in compliant patients. Comorbidity appeared to alter prognosis by increasing the prevalence of poor compliance. The majority of patients receiving lithium and divalproex who required additional treatment were depressed, suggesting that the frequent recurrence of depression is the primary unmet need in patients with rapid cycling. The use of antidepressants in this population has been discouraged because of concerns about the possibility of cycle acceleration. There exists a need for a pharmacotherapy that not only possesses marked acute antidepressant properties, but that does so without inducing switching or cycle acceleration. A double-blind, placebo-controlled trial of lamotrigine monotherapy in bipolar I depression has demonstrated efficacy without causing switching at a rate exceeding placebo; however, this initial study excluded patients with rapid cycling. To explore the efficacy of lamotrigine in rapid cycling, a recent multicenter study has examined lamotrigine as a maintenance therapy for this population. The results indicate that lamotrigine may be a useful treatment for patients with rapid-cycling bipolar II disorder and that this drug has begun to address this unmet need.

Anticonvulsants↗
PubMed2000

Current concepts in rapid cycling bipolar disorder.

The rapid-cycling variant of bipolar disorder (RCBD) has been variably defined, with episode frequencies ranging from several per day to a minimum of four per year. It is diagnosed disproportionately in women with bipolar II disorder. Its time of onset may be in childhood, adolescence, or adulthood. It appears to be treatment refractory, but controlled trials are lacking. Concurrent treatment with lithium and an antiepileptic drug is considered the current mainstay of treatment, and antidepressants are discouraged. Controlled trials in homogeneous cohorts of RCBD patients are needed. Preliminary data suggest that two or more mood stabilizers are required for adequate control.

Adolescent↗
PubMed1999

Controlled trials in bipolar I depression: focus on switch rates and efficacy.

Until recently, the rate at which patients switch from bipolar depression to the manic or hypomanic phase of the disorder during treatment with antidepressant medications was poorly defined. The completion of three large-scale, double-blind controlled trials in bipolar I depression has improved understanding of this phenomenon. The low switching rates observed in these studies of lamotrigine, paroxetine and moclobemide may indicate a special application of these drugs in the management of patients prone to antidepressant-induced switching. These studies also confirm prior suggestions that tricyclic antidepressants present the highest risk of switching. At present there is no consensus over the optimal definition of switching. Standardising the definition may lead to improvements in the clinical management of bipolar disorder.

Antidepressive Agents↗
PubMed1998

Clinical studies on the use of lamotrigine in bipolar disorder.

New mood stabilizers that possess efficacy in the depressed phase of bipolar disorder are needed. The use of marketed antidepressants puts bipolar patients at some increased risk for drug-induced hypomania/mania and rapid cycling. During the development of the antiepileptic, lamotrigine, the drug was observed to improve mood, alertness, and social interactions in some patients with epilepsy. These early observations provided the rationale for investigations into lamotrigine's potential efficacy in bipolar disorder. There are now 14 open clinical reports involving a total of 207 lamotrigine-treated patients with bipolar disorder that suggest this drug possesses a broad spectrum of efficacy in the management of the depressed, hypomanic, manic, and mixed phases of bipolar disorder. In an attempt to replicate and extend these preliminary open-label prospective findings, a series of multicenter, double-blind, placebo-controlled studies evaluating the efficacy and dose-response relationships of lamotrigine in the various phases of the illness, including both acute and maintenance designs in both bipolar I and II disorder, is ongoing.

Anticonvulsants↗
PubMed1994

The prevalence of akathisia in patients receiving stable doses of clozapine.

BACKGROUND: Akathisia is a common side effect of traditional neuroleptic drugs and is associated with medication refusal and impulsive behavior. While our previous experience indicates that clozapine is effective in treating persistent akathisia, two controlled studies indicate vastly different prevalence rates of akathisia (7% vs. 40%) in patients receiving clozapine. METHOD: We used the Barnes Rating Scale for Drug-Induced Akathisia to estimate the prevalence of akathisia in patients receiving stable doses of clozapine alone (N = 29) in a state hospital. Measurements were also made of manifest psychopathology (Brief Psychiatric Rating Scale) and tardive dyskinesia (Abnormal Involuntary Movement Scale). RESULTS: Two patients (6.8%) receiving clozapine were rated as having akathisia. Only 4 (28.6%) of the 14 subjects with a history of moderate-to-severe tardive dyskinesia on traditional neuroleptic drugs continued to show current evidence of tardive dyskinesia, and in 10 patients (71.4%) there was no evidence of the syndrome (p < .002). In the 4 subjects with tardive dyskinesia there was amelioration to a milder form of the syndrome. There were no new cases of tardive dyskinesia among clozapine-treated subjects. CONCLUSION: These data support the low prevalence of akathisia in patients receiving stable doses of clozapine monotherapy. There is further support that clozapine has an ameliorating effect on tardive dyskinesia associated with traditional neuroleptic drugs. These and other data indicate the need for a controlled trial of clozapine in patients experiencing persistent and disabling akathisia on traditional neuroleptic drugs.

Adult↗
PubMed1987

Alcoholics' self-assessment of their neuropsychological functioning in everyday life.

Self-reports of impairment in everyday cognitive and perceptuomotor functioning for the 6 months that preceded treatment were investigated in 60 male, middle-aged alcoholics and for a comparable time period in 60 nonalcoholic controls matched on age, education, and Shipley Vocabulary age. Alcoholics reported significantly more everyday impairment than did controls in memory, higher cognitive functions, language skills, and perceptual-motor function. Laboratory tests of neuropsychological performance revealed that the alcoholics were significantly poorer than controls on measures of memory, higher cognitive functions, and overall neuropsychological functioning, but test performances essentially were uncorrelated with self-reported everyday impairment and with self-reported levels of depression and anxiety. However, in both groups, measures of depression and anxiety were correlated significantly with self-perception of impairment. In alcoholics, quantity-frequency of drinking (QFI) was also correlated with reported impairment; chronicity was not. Multiple regression analyses indicate that in alcoholics, both quantity-frequency measures of alcohol intake and affective distress (depression, anxiety) made independent and roughly equal contributions to reported everyday impairment; in controls, only affective distress contributed significantly.

Activities of Daily Living↗
PubMed1982

Locus of control and neuropsychological performance in chronic alcoholics.

Correlated neuropsychological performance and three dimensions of Locus of Control (LOC) were examined in 62 hospitalized male chronic alcoholics and 24 non-alcoholic males drawn from the community. Performance deficits in alcoholic Ss correlated significantly with high scores on the Chance (LOC-C) and Powerful Others (LOC-PO) scales for approximately half of the measures employed, while no such correlations were significant in the controls. Correlations between performance and scores on the Internal (LOC-I) scale were negligible. Controls scored significantly higher than alcoholics on the Internal dimension; Chance and Powerful Others orientation were not significantly different in the two groups. From these and other results we conclude: (a) alcoholics and controls manifest similar but not identical LOC orientations; (b) alcoholics and controls show different relationships between neuropsychological performance and LOC orientation; and (c) the correlation between LOC variables and performance in alcoholics cannot account for the widespread differences in performance levels between the two groups.

Alcoholism↗
PubMed1982

Verbal and visuospatial performance and aging: a neuropsychological approach.

The hypothesis that aging and hemispheric laterality interact to produce relatively greater decrements in older individuals in right hemispheric dominant (visuospatial) than left hemispheric dominant (verbal) tasks was examined in 24 early middle-aged (M = 37.6 yr) and 24 older (M = 71.2 yr) males equated for education. Participants performed structurally similar verbal and visuospatial paired-associated learning tasks (the Stark test) that have been found sensitive to left and right hemispheric dysfunction, respectively. They were also given the Shipley Institute for Living Scale and the Memory-for-Designs Test. No group differences were present on the Shipley verbal age scale, but the older group had significantly lower Shipley abstraction ages and memory-for-designs scores. They made more errors than the middle-aged group on both the verbal and visuospatial learning tasks. Similar patterns were found when the data were reanalyzed by decade cohorts. These data do not support the notion of a laterality effect associated with aging.

Adult↗