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Biomedical subjects

Del D Miller

Publications and source records attributed to Del D Miller.

12 recordsLinked to original sources
PubMed2006

Baseline neurocognitive deficits in the CATIE schizophrenia trial.

Neurocognition is moderately to severely impaired in patients with schizophrenia. However, the factor structure of the various neurocognitive deficits, the relationship with symptoms and other variables, and the minimum amount of testing required to determine an adequate composite score has not been determined in typical patients with schizophrenia. An 'all-comer' approach to cognition is needed, as provided by the baseline assessment of an unprecedented number of patients in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) schizophrenia trial. From academic sites and treatment providers representative of the community, 1493 patients with chronic schizophrenia were entered into the study, including those with medical comorbidity and substance abuse. Eleven neurocognitive tests were administered, resulting in 24 individual scores reduced to nine neurocognitive outcome measures, five domain scores and a composite score. Despite minimal screening procedures, 91.2% of patients provided meaningful neurocognitive data. Exploratory principal components analysis yielded one factor accounting for 45% of the test variance. Confirmatory factor analysis showed that a single-factor model comprised of five domain scores was the best fit. The correlations among the factors were medium to high, and scores on individual factors were very highly correlated with the single composite score. Neurocognitive deficits were modestly correlated with negative symptom severity (r=0.13-0.27), but correlations with positive symptom severity were near zero (r<0.08). Even in an 'all-comer' clinical trial, neurocognitive deficits can be assessed in the overwhelming majority of patients, and the severity of impairment is similar to meta-analytic estimates. Multiple analyses suggested that a broad cognitive deficit characterizes this sample. These deficits are modestly related to negative symptoms and essentially independent of positive symptom severity.

Adult↗
PubMed2006

The relationship between P-glycoprotein (PGP) polymorphisms and response to olanzapine treatment in schizophrenia.

P-glycoprotein (PGP) is a polymorphic efflux transporter located on the blood brain barrier that potentially affects the penetration of atypical antipsychotics into the central nervous system. Increased antipsychotic penetration to the primary site of activity may result in greater symptom improvement or the occurrence of side effects. This investigation examined the relationship between three common PGP polymorphisms (C1236T, G2677TA, and C3435T) and response to 6 weeks of open-label olanzapine treatment in patients with schizophrenia. Individuals with a PGP T allele at any of these polymorphisms would be expected to have greater antipsychotic penetration through the blood brain barrier, due to lower PGP activity. Forty-one patients were included in this reanalysis. For subjects in the 3435T allele carrier group, the plasma olanzapine level alone was positively associated with percent change in Brief Psychiatric Rating Scale score (p = 0.02). This relationship was not seen for the 3435CC group (p = 0.583). A similar trend was observed for negative symptom reduction, olanzapine plasma concentration, and the 3435T allele (p = 0.06), but this relationship did not meet statistical significance. There was no relationship between the PGP genotypes and changes in weight over the course of this 6 week study. The analysis using C1236T or G2677AT genotypes gave similar results, due to linkage of these polymorphisms.PGP polymorphisms may affect the penetration of olanzapine into the central nervous system as seen by a relationship between the 3435T allele, olanzapine plasma levels, and reduction in the positive symptoms of schizophrenia. This may stem from greater olanzapine central nervous system latency due to the presence of the 3435T allele and reduced PGP activity. The PGP C3435T genotype may help to determine positive symptom reduction from olanzapine clinically, but these findings should be replicated in a larger sample of subjects.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Substance use in persons with schizophrenia: baseline prevalence and correlates from the NIMH CATIE study.

This study examined baseline correlates of substance use in the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness project. Approximately 60% of the sample was found to use substances, including 37% with current evidence of substance use disorders. Users (with and without substance use disorders), compared with nonusers, were significantly more likely to be male, be African-American, have lower educational attainment, have a recent period of homelessness, report more childhood conduct problems, have a history of major depression, have lower negative symptom and higher positive symptom scores on the Positive and Negative Syndrome Scale, and have a recent illness exacerbation. Individuals with comorbid substance use disorders were significantly more likely to be male, report more childhood conduct problems, have higher positive symptom scores on the Positive and Negative Syndrome Scale, and have a recent illness exacerbation. These analyses suggest that substance use disorders in schizophrenia are especially common among men with a history of childhood conduct disorder problems and that childhood conduct disorder problems are potent risk factors for substance use disorders in schizophrenia.

Antipsychotic Agents↗
PubMed2006

Baseline use of concomitant psychotropic medications to treat schizophrenia in the CATIE trial.

OBJECTIVE: This study examined the prevalence and correlates of concomitant psychotropic medications and use of anticholinergic drugs to treat schizophrenia. METHODS: Concomitant medication use was studied at baseline for participants in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial. RESULTS: Of the 1,380 patients with baseline medication data, 82 percent were taking psychotropic medications. Of this group, 6 percent were taking two antipsychotics (one first generation and one second generation); 38 percent, antidepressants; 22 percent, anxiolytics; 4 percent, lithium, and 15 percent, other mood stabilizers. The strongest predictors of taking several medications were having anxiety or depression, being female, and taking second-generation antipsychotics. Conversely, African Americans and those with better neurocognitive functioning were less likely to be taking several concomitant psychotropic medications. In some cases symptoms that were likely targets of polypharmacy, such as depression, remained prominent, suggesting only partial response. CONCLUSIONS: Concomitant use of psychotropic medications to treat people with schizophrenia is common. Empirical data demonstrating the effectiveness of many of these agents for this population are lacking.

Adult↗
PubMed2006

Substance use and psychosocial functioning in schizophrenia among new enrollees in the NIMH CATIE study.

OBJECTIVE: This study examined the relationship between substance use and psychosocial functioning in schizophrenia. METHODS: Participants were enrolled in the Clinical Antipsychotic Trials of Intervention Effectiveness. This study used baseline assessments and examined psychosocial functioning assessed by the Quality of Life Scale. Participants were classified as being abstinent, using substances, or having a substance use disorder. RESULTS: Of the 1,460 participants, 23 percent used substances and 37 percent had a substance use disorder. Of the 544 with a substance use disorder, 87 percent used alcohol, 44 percent used marijuana, and 36 percent used cocaine. Compared with participants who used substances, those with a substance use disorder had higher rates of polysubstance use. Compared with those who were abstinent, those who used substances had higher overall psychosocial functioning, and those with a substance use disorder had similar overall functioning but lower scores on the common objects and activities subscales. Among participants with a substance use disorder, those who used cocaine had lower overall functioning. CONCLUSIONS: Compared with abstinence, substance use and substance use disorder, unless they involved cocaine use, were generally associated with higher or equivalent overall psychosocial functioning. Patterns of substance use were similar to those in the community, suggesting that treatment of substance use disorders in schizophrenia should focus on reconnecting substance users to nonusing peer groups.

Adult↗
PubMed2005

Clinical correlates of tardive dyskinesia in schizophrenia: baseline data from the CATIE schizophrenia trial.

OBJECTIVE: To examine the clinical characteristics of individuals with schizophrenia that develop tardive dyskinesia (TD) associated with antipsychotic treatment. METHODS: Baseline data on 1460 patients with schizophrenia were collected as part of the Clinical Antipsychotic Trials of Intervention Effectiveness schizophrenia study. Subjects who met Schooler-Kane criteria for probable TD were compared to those without TD. Multiple regression analyses were used to examine the relationship between TD and clinical variables. RESULTS: 212 subjects met the Schooler-Kane criteria for probable TD and 1098 had no history or current evidence of TD. Subjects with TD were older, had a longer duration of receiving antipsychotic medication, and were more likely to have been receiving a conventional antipsychotic and an anticholinergic agent. After controlling for important baseline covariates, diabetes mellitus (DM) and hypertension did not predict TD, whereas substance abuse significantly predicted TD. Differences in cognitive functioning were not significantly different after controlling for baseline covariates. The TD subjects also had higher ratings of psychopathology, EPSE, and akathisia. CONCLUSION: Our results confirm the established relationships between the presence of TD and age, duration of treatment with antipsychotics, treatment with a conventional antipsychotic, treatment with anticholinergics, the presence of EPS and akathisia, and substance abuse. Subjects with TD had higher ratings of psychopathology as measured by the PANSS. We found no support for DM or hypertension increasing the risk of TD, or for TD being associated with cognitive impairment.

Antipsychotic Agents↗
PubMed2005

Clinicians' recognition of the metabolic adverse effects of antipsychotic medications.

There is a growing concern regarding the propensity of second generation antipsychotics (SGAs) to induce weight gain and metabolic adverse effects. Recent consensus guidelines have recommended assessment and monitoring procedures to appropriately detect and manage these adverse effects. This study addresses the appreciation and readiness of clinicians to implement management guidelines for these adverse effects. Respondents indicated awareness of the risks of treatment with SGAs. The extent of monitoring for metabolic adverse effects was low and inconsistent across measures and in frequency of evaluation. Ongoing efforts are needed to support and encourage change in clinician practice.

Antipsychotic Agents↗
PubMed2005

Clozapine-induced weight gain associated with the 5HT2C receptor -759C/T polymorphism.

Weight gain has been documented as a significant adverse effect associated with many of the atypical antipsychotic medications. Several recent reports have linked a -759C/T polymorphism of the 5HT2C receptor gene and obesity as well as chlorpromazine, risperidone, and clozapine induced to weight gain. This aim was to determine the association between changes in body mass index (BMI) during clozapine treatment and the -759C/T polymorphism of the 5HT2C receptor gene. This study included 41 patients with treatment-refractory schizophrenia (DSM-IV) who were followed prospectively during treatment with clozapine. Weight and height measurements were obtained prior to starting clozapine and after 6-months of treatment. Genomic DNA was isolated from a whole blood sample and analyzed for the -759C/T polymorphism of the 5HT2C receptor gene. A chi(2) analysis comparing whether or not the subjects carried a -759T allele in subjects grouped as having an increase of more or less than 7% of their baseline BMI during treatment with clozapine found that the presence of the -759T allele was significantly higher in subjects with less than or equal to a 7% increase in baseline BMI compared to those with a greater than 7% increase in BMI. A multiple linear regression analysis showed that both baseline BMI and the presence or absence of the -759T allele had significant effects on 6-month BMI. The T allele may have a protective function in preventing significant weight gain from clozapine. Subjects without the -759T variant allele were at a greater risk for weight gain from clozapine over 6-months compared to those with the -759T allele.

Adult↗
PubMed2004

The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2003 update.

BACKGROUND: The Texas Medication Algorithm Project (TMAP) has been a public-academic collaboration in which guidelines for medication treatment of schizophrenia, bipolar disorder, and major depressive disorder were used in selected public outpatient clinics in Texas. Subsequently, these algorithms were implemented throughout Texas and are being used in other states. Guidelines require updating when significant new evidence emerges; the antipsychotic algorithm for schizophrenia was last updated in 1999. This article reports the recommendations developed in 2002 and 2003 by a group of experts, clinicians, and administrators. METHOD: A conference in January 2002 began the update process. Before the conference, experts in the pharmacologic treatment of schizophrenia, clinicians, and administrators reviewed literature topics and prepared presentations. Topics included ziprasidone's inclusion in the algorithm, the number of antipsychotics tried before clozapine, and the role of first generation antipsychotics. Data were rated according to Agency for Healthcare Research and Quality criteria. After discussing the presentations, conference attendees arrived at consensus recommendations. Consideration of aripiprazole's inclusion was subsequently handled by electronic communications. RESULTS: The antipsychotic algorithm for schizophrenia was updated to include ziprasidone and aripiprazole among the first-line agents. Relative to the prior algorithm, the number of stages before clozapine was reduced. First generation antipsychotics were included but not as first-line choices. For patients refusing or not responding to clozapine and clozapine augmentation, preference was given to trying monotherapy with another antipsychotic before resorting to antipsychotic combinations. CONCLUSION: Consensus on algorithm revisions was achieved, but only further well-controlled research will answer many key questions about sequence and type of medication treatments of schizophrenia.

Algorithms↗
PubMed2004

Atypical antipsychotics: sleep, sedation, and efficacy.

Patients with schizophrenia often suffer from sleep disturbances such as excessive sleeping and insomnia. Common medications for schizophrenia can have a sedative effect on patients. Not all antipsychotic medications have the same sedative effect, which is related to dosage and affinity for histamine H1 receptors. Studies have shown that, compared with conventional antipsychotics, atypical antipsychotics such as risperidone, olanzapine, quetiapine, and ziprasidone generally cause less sedation yet are as effective in controlling psychosis and agitation. Sedation can be troublesome to patients who are trying to become re-integrated into society and interfere with their treatment regimen. Both persistent sedation and chronic insomnia can be managed by the physician.

Journal Article↗
PubMed2002

The effects of neuroleptic medications on basal ganglia blood flow in schizophreniform disorders: a comparison between the neuroleptic-naïve and medicated states.

BACKGROUND: Previous studies indicate that basal ganglia volumes of first-episode neuroleptic-naïve patients with schizophrenia are smaller than those of normal control subjects. Subsequent exposure to neuroleptic medication appears to induce volumetric change. Possible reasons for this include differences in blood flow and metabolism between the neuroleptic-naïve and medicated states. METHODS: We used positron emission tomography (PET) to measure blood flow to the caudate and putamen, in a sample of 29 neuroleptic-naïve patients with schizophreniform disorders and 29 matched control subjects. We also studied a subset of the patient sample (n = 13), comparing their "before" versus "on" medication PET scans. RESULTS: We did not find a significant difference in blood flow to the caudate and putamen between neuroleptic-naïve patients and control subjects even after controlling for whole brain blood flow; however, in the subset of 13 patients compared in the "on" versus "off" medication states, there was a statistically significant increase in blood flow to both the caudate and putamen. CONCLUSIONS: Before treatment, there appears to be no difference in striatal blood flow between first-episode neuroleptic-naïve patients and healthy volunteers, but there appears to be a significant increase in blood flow to the striatum after the treatment is initiated.

Adult↗