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Biomedical subjects

J Volavka

Publications and source records attributed to J Volavka.

At least 37 records · Page 2Linked to original sources
PubMed1998

Change in plasma prolactin and clinical response to haloperidol in schizophrenia and schizoaffective disorder.

There has been a long-standing interest in plasma prolactin as a potential in vivo indicator of blockade of tuberoinfundibular D2 dopamine receptors. Potential relationships between prolactin response and neuroleptic treatment have been obscured by the use of high doses which have caused prolactin to plateau. With lower doses of neuroleptic now commonly in use, prolactin may be more valuable as a correlate of clinical response. In this study, 23 acutely exacerbated schizophrenic and schizoaffective patients were washed out for at least 6 days and were then treated with haloperidol to achieve fixed low to moderate plasma levels under double-blind conditions. Clinical response, plasma prolactin, and haloperidol plasma levels were measured weekly for 3 weeks. Clinical symptoms at endpoint were related to both prolactin change and final prolactin level during haloperidol treatment. Specifically, fewer symptoms at endpoint were associated with a greater increase in prolactin over time and a higher prolactin level at endpoint. Thus, prolactin increase caused by low to moderate doses of haloperidol may be a correlate of endpoint symptomatology. As lower doses of typical neuroleptics are now in use, prolactin response as a predictor of clinical response may have more clinical utility. Further study of prolactin and clinical response to typical neuroleptics should focus on low neuroleptic doses.

Adult↗
PubMed1998

Hypothesis testing: is clozapine's superior efficacy dependent on moderate D2 receptor occupancy?

BACKGROUND: How clozapine exerts superior antipsychotic efficacy in treatment-resistant schizophrenia is not known. Moderate (rather than "full") occupancy of D2 postsynaptic receptors may be crucial, perhaps by achieving a more effective D1/D2 or serotonin-2a/D2 ratio. The objective of this study was to test the moderate occupancy hypothesis of clozapine's superior efficacy. METHODS: Data from the New York effectiveness of clozapine study were used to compare 6-week clozapine treatment results in patients discontinuing oral neuroleptic medication with similar patients discontinuing long-acting depot neuroleptic. The latter group is assured "full" D2 occupancy during the 6-week clozapine treatment. RESULTS: If moderate occupancy is crucial for superior efficacy, the oral discontinuation group should manifest more improvement. Both groups showed the 6-week improvement expected with clozapine therapeutics [31% and 29% reduction in Brief Psychiatric Rating Scale (BPRS) scores in the depot and oral groups, respectively]. An analysis of covariance (for baseline BPRS) revealed no difference in change scores (df = 1,100; F = 0.17; p = ns). CONCLUSIONS: The reduced D2 occupancy hypothesis is rejected.

Antipsychotic Agents↗
PubMed1998

Association between catechol O-methyltransferase genotype and violence in schizophrenia and schizoaffective disorder.

OBJECTIVE: The authors previously reported a relationship between an allele encoding the low activity variant of catechol O-methyltransferase (COMT) and aggressive behavior in schizophrenic patients. This study replicates and extends these findings by using more direct measures of violent behavior. METHOD: Fifty-five white patients (34 men, 21 women) with DSM-IV diagnoses of schizophrenia or schizoaffective disorder were selected to form two groups (violent and nonviolent) on the basis of history of aggressive behavior. COMT genotypes were determined by restriction fragment length polymorphism analysis. RESULTS: A significant association was found between COMT genotype and history of violent behavior. Sixty-four percent of patients homozygous for the low-activity COMT allele were violent; 80% of patients homozygous for the high-activity allele were nonviolent. CONCLUSIONS: The gene determining the activity of an important regulatory enzyme in catecholamine inactivation is associated with violent behavior in patients with schizophrenia and schizoaffective disorder.

Adult↗
PubMed1997

Effect of neuroleptic treatment on depressive symptoms in acute schizophrenic episodes.

This study examined depressive symptoms in acute schizophrenic episodes and their relationship to neuroleptic treatment. Sixty-three depressed and 62 non-depressed acutely exacerbated schizophrenic patients were evaluated with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, the Simpson-Angus Extrapyramidal Scale, and the Hamilton Rating Scale for Depression. Subjects were then randomly assigned to different haloperidol plasma levels and followed for 3 weeks. Overall, depression improved with treatment of the acute psychosis, but a positive association between extrapyramidal side effects and depressive symptoms emerged over time. Depressive symptoms tended to be positively related to haloperidol plasma levels. The results suggest that depressive symptoms in schizophrenia are heterogeneous in origin; while neuroleptics can ameliorate depressive symptoms inherent in the acute schizophrenic episode, they can also contribute to depression.

Adult↗
PubMed1997

Analysis of a functional catechol-O-methyltransferase gene polymorphism in schizophrenia: evidence for association with aggressive and antisocial behavior.

We have recently characterized a functional polymorphism in the catechol-O-methyltransferase (COMT) gene that is responsible for substantial variability in COMT enzymatic activity found in humans. A common low-activity variant of the enzyme contains a methionine residue at amino acid 158 of membrane-bound COMT whereas the common high activity variant has a valine at this site. Considering the role of COMT in dopamine metabolism and the involvement of dopaminergic pathways in the pathogenesis of schizophrenia and violence, we screened 37 patients with schizophrenia to determine whether or not a behavioral association with the COMT polymorphism exists. Patients were assessed for dangerousness on the basis of a history of violent and threatening behavior, crime, cocaine and alcohol abuse, and other antisocial behaviors. We found that schizophrenic patients who were homozygous for the low activity allele were judged by their psychiatrists to be at higher risk for aggressive and dangerous behavior than those who were homozygous for the high activity allele (Kruskal-Wallis statistic = 10.43; P = 0.003).

Adult↗
PubMed1997

History of violent behaviour and schizophrenia in different cultures. Analyses based on the WHO study on Determinants of Outcome of Severe Mental Disorders.

BACKGROUND: Information on patterns and correlates of the violent behaviour of individuals with schizophrenia is largely limited to populations in developed countries. Data from a World Health Organization epidemiological study of schizophrenia and related disorders, the Determinants of Outcome of Severe Mental Disorders (DOSMD), presented an opportunity to study patterns of violence across multinational settings. METHOD: Centres in 10 countries participated in the DOSMD study. An incidence sample of 1017 patients with schizophrenia who had their first-in-lifetime contact with a helping agency as a result of their psychotic symptoms was obtained. Data were available on their history of violent behaviour, substance use, and demographics. RESULTS: The occurrence rate of assault in the entire cohort was 20.6 per hundred, but the rate was three times higher in the developing countries (31.5 per hundred) than in developed countries (10.5 per hundred). History of assault was associated with positive symptoms, such as excitement and auditory hallucinations, and with serious alcohol problems. CONCLUSIONS: The cultural context and the specific characteristics of the disease in individuals with schizophrenia may interactively affect rates of violent behaviour.

Adolescent↗
PubMed1996

The electroencephalogram after alcohol administration in high-risk men and the development of alcohol use disorders 10 years later.

BACKGROUND: In 1979 through 1980, electroencephalographic (EEG) responses to an alcohol challenge in 19 year-old sons of alcoholics as well as in sons of nonalcoholic control subjects were examined. The familial risk status of the subjects and greater EEG sensitivity to alcohol were hypothesized to predict the development of alcoholism 10 years later. METHODS: In 1990 through 1992, diagnostic interviews were completed to ascertain alcohol and other substance use disorders in these subjects and to update their family history. RESULTS: Updated family history of alcoholism predicted the development of substance dependence. Density of alcoholic relatives (the number of alcoholic relatives divided by the number of known relatives) was positively related to the severity of alcohol use disorders in the probands. Contrary to expectation, a greater EEG response at age 19 years was not related to the later development of alcohol dependence. Instead, the opposite was observed: a smaller EEG alpha frequency response to alcohol at age 19 years was related to the development of alcohol dependence and high quantity and frequency of alcohol consumption 10 years later. CONCLUSIONS: Lower EEG response to a small dose of alcohol may be associated with the later development of alcohol dependence. This result is based on a small number of subjects and should be interpreted with caution. Although this result is opposite to our 1980 hypothesis, it is consistent with much of the recent literature.

Adult↗
PubMed1996

Placebo washout in trials of antipsychotic drugs.

For antipsychotic phase 3 clinical trials, we compare the relative merits of a placebo washout period with an alternate design strategy using a low-dose antipsychotic treatment. Evaluations are made with respect to the achievement of specific clinical trial design goals including the effect on power for detecting between-treatment and within-treatment pre-post differences. The relative merits of these two designs are discussed separately for those patients who enter the initial leadin period after withdrawal from previous antipsychotic medication and for those not on medication immediately before that period.

Antipsychotic Agents↗
PubMed1996

Positive and negative symptoms: is their change related?

The objective of this study was to investigate the relationship between change in positive and negative symptoms over time during haloperidol treatment. Subjects were 178 acutely exacerbating chronic schizophrenia patients participating in a clinical trial of haloperidol. Positive and negative symptoms were measured by the positive and negative symptom clusters of the Brief Psychiatric Rating Scale and by the Scales for the Assessment of Positive and Negative Symptoms. Hierarchical linear model analysis was used to estimate symptom-change trajectories of positive and negative symptoms over time in individual patients and to investigate the inter-relationship between these trajectories. Results indicate that positive and negative symptom-change trajectories over time were closely associated. This result did not depend on extrapyramidal side effects, depression, or the baseline balance of positive and negative symptoms. Thus, our study suggests that in acutely exacerbating schizophrenia patients, changes of positive and negative symptoms over time are related during the initial phase of the pharmacological treatment. This relationship may not extend to other treatment paradigms or beyond the initial phase of the treatment.

Adult↗
PubMed1996

Effect of varying haloperidol plasma levels on negative symptoms in schizophrenia and schizoaffective disorder.

Double-blind haloperidol was administered during two consecutive 3-week periods to 65 patients with acutely exacerbating schizophrenia or schizoaffective disorder. Two plasma levels were targeted. low (2 ng/mL) and moderate (10 ng/mL). The subjects were randomly assigned to four treatment sequences (low-low, low-moderate, moderate-moderate, or moderate-low). Data from 28 patients were available for the analyses of the second study period. In that period, decrease of plasma levels reduced mild but not severe negative symptoms. Thus, lowering of the plasma levels after the first 3 weeks of treatment may improve mild negative symptoms. Conversely, increasing the plasma levels may make mild negative symptoms worse.

Adult↗
PubMed1995

Serotonin in violent patients with schizophrenia.

CSF levels of 5-hydroxyindolacetic acid (5-HIAA), the serotonin metabolite, were assayed in 10 violent and 10 matched nonviolent patients with schizophrenia. Mean group levels of 5-HIAA in cerebrospinal fluid were found to be nearly identical. Possible explanations, including effects of medications, are discussed.

Adult↗
PubMed1995

Plasma haloperidol levels and clinical effects in schizophrenia and schizoaffective disorder.

BACKGROUND: Plasma haloperidol levels between 5 and 11 ng/mL may be clinically optimal for acutely exacerbated schizophrenia, but the evidence for this therapeutic window has been inconsistent. METHODS: Haloperidol was administered in a double-blind manner during two consecutive 3-week experimental periods to 65 patients with acutely exacerbated schizophrenia or schizoaffective disorder. Two plasma levels were targeted: "low" (2 ng/mL) and "moderate" (10 ng/mL). The subjects were randomly assigned to four treatment sequences (low-low, low-moderate, moderate-moderate, or moderate-low). RESULTS: In the first 3 weeks, the antipsychotic efficacy of haloperidol increased with plasma levels up to approximately 12 ng/mL. In the second 3 weeks, decrease of plasma levels reduced negative symptoms. CONCLUSION: For most patients, plasma levels not exceeding 12 ng/mL yield the best results in the first 3 weeks of treatment. Subsequent lowering of the plasma levels may improve negative symptoms.

Adult↗
PubMed1995

Effect of risperidone on hostility in schizophrenia.

The objective was to examine effects of risperidone on hostility and compare these effects with those of haloperidol. On the basis of risperidone's pharmacologic profile, we hypothesized that risperidone has a selective effect on hostility and that this effect is greater than that of haloperidol. The data were obtained in a multicenter clinical trial of risperidone under placebo-controlled, double-blind conditions (duration, 9 weeks). The patients were 139 patients with the diagnosis of DSM-III-R schizophrenia. Hostility was measured by the "hostility" item of the Positive and Negative Syndrome Scale. Change in hostility served as a dependent variable in the analyses. Change in "psychosis" was applied as a covariate; it helped us examine changes in hostility that were unrelated to change in psychosis (selective effect). Risperidone had a greater selective effect on hostility than did haloperidol or placebo. This finding should encourage tests of risperidone as a treatment for patients who show frequent overt physical aggression.

Adolescent↗
PubMed1995

Characteristics of state hospital patients arrested for offenses committed during hospitalization.

OBJECTIVE: The study was a preliminary exploration of the relatively new phenomenon of arresting psychiatric inpatients for offenses committed in the hospital. METHODS: A retrospective record review at two New York state hospitals identified all 73 inpatients arrested over a 30-month period for an offense committed while they were hospitalized. Logistic regression was used to compare arrestees with a control group of 1,438 non-arrested inpatients. RESULTS: The number of arrests at the two hospitals significantly increased over the study period. Seventy-nine percent of arrests resulted from a violent incident. At least 68 percent of arrestees had been arrested previously. Compared with the control group, arrestees were more likely to be young, male, and black and to have a shorter length of stay. Axis I diagnoses did not differentiate arrestees from control patients. Ninety percent of arrestees had a diagnosis of substance use or personality disorder or both. The sample more closely resembled the population of criminal offenders in the community than the psychiatric inpatient population. Prosecution resulted in jail or prison terms for 11 percent of arrestees. CONCLUSIONS: This descriptive preliminary study was limited by its retrospective nature and reliance on records of varying quality. Although the increase in arrests is clear, the cause of the increase and the impact of arrests on arrestees and hospitals remain to be clarified.

Adult↗