Biomedical subjects

Delbert G Robinson

Publications and source records attributed to Delbert G Robinson.

14 recordsLinked to original sources

PubMed2006

Randomized comparison of olanzapine versus risperidone for the treatment of first-episode schizophrenia: 4-month outcomes.

OBJECTIVE: The authors compared 4-month treatment outcomes for olanzapine versus risperidone in patients with first-episode schizophrenia spectrum disorders. METHOD: One hundred twelve subjects (70% male; mean age=23.3 years [SD = 5.1]) with first-episode schizophrenia (75%), schizophreniform disorder (17%), or schizoaffective disorder (8%) were randomly assigned to treatment with olanzapine (2.5-20 mg/day) or risperidone (1-6 mg/day). RESULTS: Response rates did not significantly differ between olanzapine (43.7%, 95% CI=28.8%-58.6%) and risperidone (54.3%, 95% CI=39.9%-68.7%). Among those responding to treatment, more subjects in the olanzapine group (40.9%, 95% CI=16.8%-65.0%) than in the risperidone group (18.9%, 95% CI=0%-39.2%) had subsequent ratings not meeting response criteria. Negative symptom outcomes and measures of parkinsonism and akathisia did not differ between medications. Extrapyramidal symptom severity scores were 1.4 (95% CI=1.2-1.6) with risperidone and 1.2 (95% CI=1.0-1.4) with olanzapine. Significantly more weight gain occurred with olanzapine than with risperidone: the increase in weight at 4 months relative to baseline weight was 17.3% (95% CI=14.2%-20.5%) with olanzapine and 11.3% (95% CI=8.4%-14.3%) with risperidone. Body mass index at baseline and at 4 months was 24.3 (95% CI=22.8-25.7) versus 28.2 (95% CI=26.7-29.7) with olanzapine and 23.9 (95% CI=22.5-25.3) versus 26.7 (95% CI=25.2-28.2) with risperidone. CONCLUSIONS: Clinical outcomes with risperidone were equal to those with olanzapine, and response may be more stable. Olanzapine may have an advantage for motor side effects. Both medications caused substantial rapid weight gain, but weight gain was greater with olanzapine.

Adult↗

PubMed2006

DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients.

OBJECTIVE: All antipsychotics act on the dopamine D(2) receptor. The present study extends prior pharmacogenetic investigations of the D(2) receptor gene (DRD2) by examining, in first-episode schizophrenia patients, promoter region variation as a predictor of response time to two first-line atypical antipsychotics. METHOD: Patients experiencing their first episode of schizophrenia (N=61) were genotyped for two DRD2 promoter region polymorphisms (A-241G and -141C Ins/Del) and were randomly assigned to receive 16 weeks of treatment with either risperidone or olanzapine. Time until sustained response (two consecutive ratings without significant positive symptoms) for rare allele carriers versus wild types was examined by using Kaplan-Meier curves. RESULTS: Relative to wild type homozygotes, G carriers (A-241G) exhibited a significantly faster time until response, whereas -141C Del carriers took a significantly longer time to respond. Diplotype analysis revealed similar results. CONCLUSIONS: These findings suggest that variation in the D(2) receptor gene can, in part, explain variation in the timing of clinical response to antipsychotics in patients with first-episode schizophrenia.

Adolescent↗

PubMed2006

High-dose sertraline strategy for nonresponders to acute treatment for obsessive-compulsive disorder: a multicenter double-blind trial.

OBJECTIVE: To evaluate the efficacy and safety of high-dose sertraline for patients with obsessive-compulsive disorder (OCD) who failed to respond to standard sertraline acute treatment. METHOD: Sixty-six nonresponders to 16 weeks of sertraline treatment who met DSM-III-R criteria for current OCD were randomly assigned, in a double-blind continuation phase of a multicenter trial, either to continue on 200 mg/day of sertraline or to increase their dose to between 250 and 400 mg/day for 12 additional weeks. Efficacy measures included the Yale-Brown Obsessive Compulsive Scale (YBOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH Global OC Scale), and the Clinical Global Impressions-Severity of Illness and -Improvement (CGI-I) scales. Data were collected from July 26, 1994, to October 26, 1995. RESULTS: The high-dose (250-400 mg/day, mean final dose = 357, SD = 60, N = 30) group showed significantly greater symptom improvement than the 200-mg/day group (N = 36) as measured by the YBOCS (p = .033), NIMH Global OC Scale (p = .003), and CGI-I (p = .011). Responder rates (decrease in YBOCS score of > or = 25% and a CGI-I rating < or = 3) were not significantly different for the 200-mg/day versus the high-dose sertraline group, either on completer analysis, 34% versus 52%, or on endpoint analysis, 33% versus 40%. Both treatments showed similar adverse event rates. CONCLUSION: Greater symptom improvement was seen in the high-dose sertraline group compared to the 200-mg/day dose group during continuation treatment. Both dosages yielded similar safety profiles. Administration of higher than labeled doses of selective serotonin reuptake inhibitors may be a treatment option for certain OCD patients who fail to respond to standard acute treatment.

Adult↗

PubMed2005

Pharmacological treatments for first-episode schizophrenia.

Studies with first-episode populations offer the unique opportunity to examine the effectiveness and side effects of medications without the confounding effects of prior medication use. This review focuses upon studies of (1) treatment of the initial episode, (2) maintenance treatment issues, (3) recovery, and (4) side effects. Response rates for the initial episode are high with both conventional and new-generation antipsychotics. However, we lack data directly comparing the new-generation agents with one another for treatment of the initial episode, and data about options for patients with treatment resistance at illness onset are very limited. With the most commonly used pharmacological therapies, the course of early-phase schizophrenia is characterized by repeated relapses and a low rate of recovery. Medication treatment is also associated with a variety of side effects. Of particular concern for treatment of first-episode patients are the metabolic side effects with the new-generation antipsychotics because they occur rapidly, are very distressful to adolescents and young adults, and have long-term medical consequences. Available data support maintenance treatment to prevent relapse, but questions remain about the optimal duration of maintenance treatment, whether there are differences among the new-generation agents for maintenance treatment, and balancing the benefits of maintenance antipsychotics with their long-term side effects.

Adolescent↗

PubMed2005

White matter abnormalities in obsessive-compulsive disorder: a diffusion tensor imaging study.

CONTEXT: Several neurobiological models of obsessive-compulsive disorder (OCD) posit a primary role for dysfunction of the anterior cingulate gyrus. Both functional and structural neuroimaging studies have implicated anterior cingulate gray matter abnormalities in the pathophysiology of OCD, but there has been little investigation of the anterior cingulate white matter in this disorder. OBJECTIVE: To test the hypothesis that patients with OCD have abnormal white matter microstructure in the anterior cingulate gyrus compared with healthy volunteers as inferred from diffusion tensor imaging. Additional analyses examined group differences in white matter integrity across the entire brain. DESIGN, SETTING, AND PARTICIPANTS: Fifteen patients with a DSM-IV diagnosis of OCD and 15 healthy volunteers matched for age, sex, and handedness underwent diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy (FA), a robust intravoxel measure of water self-diffusion, was compared between groups on a voxel-by-voxel basis in the anterior cingulate white matter after standardization in Talairach space. MAIN OUTCOME MEASURES: Clinical ratings of symptom severity (ie, Yale-Brown Obsessive-Compulsive Scale) and FA. RESULTS: Compared with healthy volunteers, patients demonstrated significantly lower FA bilaterally in 3 areas of the anterior cingulate gyrus white matter. Additional analyses conducted across the rest of the brain white matter revealed lower FA bilaterally in the parietal region (supramarginal gyri), right posterior cingulate gyrus, and left occipital lobe (lingual gyrus). No areas of significantly higher FA were observed in patients compared with healthy volunteers. Lower FA in the parietal region correlated significantly with higher Yale-Brown Obsessive-Compulsive Scale scores. CONCLUSIONS: These preliminary findings provide evidence of an abnormality that involves the anterior cingulate white matter in the pathogenesis of OCD and are consistent with neurobiological models that posit a defect in connectivity in the anterior cingulate basal ganglia-thalamocortical circuit. White matter abnormalities in other brain regions may also be implicated in the neurobiology of OCD.

Adult↗

PubMed2005

Duration of untreated psychosis and time to treatment response for delusions and hallucinations.

OBJECTIVE: Duration of untreated psychosis is associated with time to treatment response among patients with schizophrenia. However, individual psychotic symptoms have not been investigated in this context. The authors examined the relationship between duration of untreated psychosis and time to response for hallucinations and delusions. METHOD: Data were available for 118 patients with first-episode schizophrenia in a longitudinal treatment study. Patients received open-label treatment with conventional antipsychotics and were followed for up to 5 years. Duration of untreated psychosis was correlated with time to response for delusions and hallucinations, and predictors of time to response were examined. RESULTS: Time to response for delusions was significantly longer than that for hallucinations. Duration of untreated psychosis was significantly correlated with time to response for delusions but not for hallucinations. In regression analyses, duration of untreated psychosis was the only predictor for time to response for delusions; it was not a predictor for hallucinations. CONCLUSIONS: The results suggest that duration of untreated psychosis may be specifically associated with time to response for delusions. This association may have clinical implications.

Adult↗

PubMed2005

White matter abnormalities in first-episode schizophrenia or schizoaffective disorder: a diffusion tensor imaging study.

OBJECTIVE: The goal of this study was to investigate brain white matter abnormalities by using diffusion tensor imaging in patients with schizophrenia or schizoaffective disorder close to illness onset. METHOD: Ten patients experiencing a first episode of schizophrenia or schizoaffective disorder and 13 healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Voxel-wise analysis was used to compare fractional anisotropy maps in the white matter of the two groups following intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy in the left internal capsule and left-hemisphere white matter of the middle frontal gyrus and posterior superior temporal gyrus. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These findings suggest that white matter pathology is present early in the course of schizophrenia and may be less pronounced than has been found in previous diffusion tensor imaging studies of patients with chronic illness. Further, these data are consistent with hypotheses regarding frontotemporal dysfunction and the failure of left-hemisphere lateralization in the pathophysiology of schizophrenia.

Adult↗

PubMed2004

Symptomatic and functional recovery from a first episode of schizophrenia or schizoaffective disorder.

OBJECTIVE: Follow-up studies have found that a substantial number of patients with schizophrenia achieve full recovery (i.e., sustained improvement in both symptoms and social/vocational functioning) when examined decades after an index admission. This study addressed recovery during the crucial early course of the illness. METHOD: Subjects in their first episode of schizophrenia or schizoaffective disorder (N=118) were assessed at baseline and then treated according to a medication algorithm. Full recovery required concurrent remission of positive and negative symptoms and adequate social/vocational functioning (fulfillment of age-appropriate role expectations, performance of daily living tasks without supervision, and engagement in social interactions). RESULTS: After 5 years, 47.2% (95% CI=36.0%-58.4%) of the subjects achieved symptom remission, and 25.5% (95% CI=16.1%-34.7%) had adequate social functioning for 2 years or more. Only 13.7% (95% CI=6.4%-20.9%) of subjects met full recovery criteria for 2 years or longer. Better cognitive functioning at stabilization was associated with full recovery, adequate social/vocational functioning, and symptom remission. Shorter duration of psychosis before study entry predicted both full recovery and symptom remission. More cerebral asymmetry was associated with full recovery and adequate social/vocational functioning; a schizoaffective diagnosis predicted symptom remission. CONCLUSIONS: Although some patients with first-episode schizophrenia can achieve sustained symptomatic and functional recovery, the overall rate of recovery during the early years of the illness is low.

Activities of Daily Living↗

PubMed2004

Recognizing and managing antipsychotic drug treatment side effects in the elderly.

Although atypical antipsychotics differ from conventional antipsychotics in their decreased ability to cause reversible drug-induced movement disorders/motor side effects such as dystonia, drug-induced parkinsonism, and akathisia and potentially persistent drug-induced movement disorders/motor side effects such as tardive dyskinesia, no antipsychotic agent completely eradicates this risk. Antipsychotic agents are frequently used in facilities for the elderly and in general hospitals to treat older patients with behavioral problems. Drug-induced movement disorders are more common and more persistent in elderly patients than in younger patients, and this problem is exacerbated by the fact that antipsychotic medications are often misused by practitioners lacking adequate psychopharmacologic training. Movement disorders can be detrimental to an elderly patient's quality of life and may transform what were otherwise routine activities into difficult tasks. Educational programs are needed to teach primary care physicians, specialists, and patients and their families how to identify and manage drug-induced movement disorders in order to achieve safer and more efficacious care for elderly patients.

Journal Article↗

PubMed2003

Clozapine as a first treatment for schizophrenia.

OBJECTIVE: The authors' goal was to explore whether clozapine given as the first antipsychotic treatment favorably affects the course of schizophrenia. METHOD: Thirty-four inpatients experiencing their first episode of schizophrenia or schizoaffective disorder were treated first with clozapine and then followed for up to 4 years. In a previous study, the authors followed patients experiencing their first episode of schizophrenia or schizoaffective disorder who were given fluphenazine as the first treatment. In the current study and the previous study, response criteria required sustained remission of positive symptoms. RESULTS: Nineteen of the 34 subjects met response criteria while taking clozapine. The median time to treatment response was 11 weeks (range=2-13). Using survival analysis, the authors determined that the cumulative response rate for the 34 patients was 66.4% at the end of 13 weeks, which is comparable to the response rate to fluphenazine in the previous study. All responses to clozapine occurred by 13 weeks. Eight (42%) of the clozapine responders discontinued clozapine before 6 months, and only six (32%) remained on clozapine for all of their time in the study. CONCLUSIONS: The authors found no benefit for clozapine over conventional antipsychotics for acute treatment of the first episode of schizophrenia or schizoaffective disorder. Long-term benefits could not be studied because of the high rate of early discontinuation of clozapine treatment.

Adolescent↗

PubMed2002

Predictors of medication discontinuation by patients with first-episode schizophrenia and schizoaffective disorder.

BACKGROUND: Enhancing medication adherence early in the course of schizophrenia and schizoaffective disorder may substantially improve long-term course. Although extensively studied in multi-episode patients, little data exist on medication adherence by first-episode patients. METHOD: Medication adherence was assessed during the first year of treatment and following recovery from the first relapse in patients treated by a standardized medication algorithm. RESULTS: During the first year of treatment, patients with poorer premorbid cognitive functioning were more likely to stop antipsychotics (t=-2.54, df=75, p=0.01). Parkinsonian side effects increased the likelihood (hazard ratio=41.22; 95% CI=2.30, 737.89; p=0.01), and better executive function decreased the likelihood (hazard ratio=0.40; 95% CI=0.18, 0.88; p=0.02) that patients discontinued maintenance medication after a first relapse. CONCLUSION: Interventions to ameliorate cognitive deficits and Parkinsonian side effects may enhance treatment adherence.

Adult↗

PubMed2002

No evidence for phenotypic variation between probands in case-control versus family-based association studies of schizophrenia.

Traditional case-control genetic association studies utilizing unrelated probands are often used interchangeably with family-based designs to detect genes for complex psychiatric disorders. This strategy may be limited, however, if significant phenotypic variation exists between probands enrolled in these two types of studies. The present study compared 37 probands enrolled in a case-control study of schizophrenia with 37 age-, sex-, and ethnically matched probands enrolled in a family-based study of schizophrenia. Age of onset of illness was compared as well as performance on a battery of cognitive tests assessing attention, working memory, executive function, and verbal memory. Results revealed no significant differences in age of onset between the two groups or on any measure of cognitive performance. These data do not support reports of significant phenotypic variation between probands in case-control and family-based studies, and suggest that studies utilizing family-based approaches may be used to replicate reports of association made with case-control designs in schizophrenia.

Adult↗

PubMed2002

Basal ganglia volumes in first-episode schizophrenia and healthy comparison subjects.

BACKGROUND: Previous studies suggest that dysfunction of cortico-striato-pallido-thalamic (CSPT) circuitry may be involved in the pathophysiology of schizophrenia but also show that basal ganglia structure is highly plastic and may be influenced by antipsychotic treatments. Controversy remains about whether basal ganglia pathology can be detected in vivo among treatment-naïve patients. We conducted a magnetic resonance imaging (MRI) study to examine basal ganglia structures and the limbic forebrain in first episode schizophrenia and healthy comparison subjects. METHODS: Fifty-one patients with first-episode schizophrenia and 28 healthy comparison subjects participated in the study. A high-resolution, special contrast (white matter nulling) MRI sequence was used to measure the caudate nucleus, nucleus accumbens, putamen, and subcommissural limbic forebrain. RESULTS: Volumes of the basal ganglia regions of interest (adjusted for total brain volume and age) did not differ significantly between the groups. Age correlated significantly with caudate and putamen volumes bilaterally in the healthy comparison group, but not among patients. CONCLUSIONS: The findings suggest that there are no volumetric abnormalities in basal ganglia before treatment in first-episode schizophrenia. The lack of a negative correlation between age and striatal volume among patients may implicate illness-associated factors that alter normal age-related changes in basal ganglia size.

Adult↗

PubMed2002

Neurocognitive correlates of response to treatment in formal thought disorder in patients with first-episode schizophrenia.

OBJECTIVE: To examine the independent contribution of executive versus semantic function to improvement in formal thought disorder after initial stabilization in a first-episode sample. BACKGROUND: Neurocognitive deficits have been suggested to predict treatment response in patients with first-episode schizophrenia. However, studies targeting putative neurocognitive mechanisms to explore improvement in positive psychotic symptoms and especially formal thought disorder are lacking. METHOD: Formal thought disorder symptoms in 81 first-episode patients with schizophrenia or schizoaffective disorder either showed significant improvement (responders > 60% change) or not (nonresponders < 60%) 6 months after initial stabilization of symptoms. These two groups were compared on neuropsychologic (n = 16), clinical (n = 15), and volumetric measures of the frontal and temporal lobes (n = 5) in univariate analyses. The variables that significantly differed between these two groups were used in a forward binary logistic regression analysis. RESULTS: As compared with nonresponders, responders were younger at time of testing, had higher verbal intelligence and reading achievement scores, higher scores on the arithmetic subtest of the Wechsler Adult Intelligence Scale-Revised, and lower number of perseverative responses on the Wisconsin Card Sort Test. Responders also had larger frontal lobe volumes than nonresponders. Only two measures (perseverative responses on the Wisconsin Card Sort Test and age at testing) entered the regression equation. Measures of semantic competency and volumetric measures of the temporal lobes were not associated with formal thought disorder improvement. CONCLUSIONS: Neurocognitive deficits are associated with treatment response in formal thought disorder in first-episode patients with schizophrenia. The improvement in formal thought disorder is more strongly linked to executive than semantic function in this sample, pointing to the salience of frontal systems in treatment response in positive psychotic symptoms.

Adult↗