PubMed Health⌕ Search

Biomedical subjects

R R Conley

Publications and source records attributed to R R Conley.

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

Olanzapine response in treatment-refractory schizophrenic patients with a history of substance abuse.

As many as half of all schizophrenic patients have abused alcohol or illicit drugs. This study determines the extent of substance abuse in a treatment-resistant population and assesses the response of this population to olanzapine treatment. Sixty patients with a DSM-III-R diagnosis of schizophrenia were included in an open 7-week trial of up to 25 mg/day of olanzapine. A history of substance abuse was present in 23 (38%) of the patients. At baseline evaluation, patients with a history of substance abuse had lower CGI scores and less negative symptomatology while having a higher rate of tardive dyskinesia. The overall group improved significantly over time. There were no differences in response between the substance-abusing (SA) and non-substance-abusing (NSA) patients as measured by the total BPRS, GGI and SANS ratings. The NSA group had significantly greater improvement in negative symptoms as measured by the BPRS negative symptom factor. Sixty-nine per cent (16/23) of the SA group and 60% (22/37) of the NSA were considered olanzapine responders by a priori criteria (p = NS). Extrapyramidal symptoms declined significantly in the overall group, but did not significantly differ between the SA and NSA groups. Treatment-refractory patients with prior substance abuse had a comparable outcome on olanzapine therapy to those with no history of abuse, as well as no increase in adverse effects. This suggests that olanzapine may be of benefit to SA patients who have a greater tendency for antipsychotic side effects and tardive dyskinesia.

Adult↗
PubMed1998

[3H]Neurotensin receptor densities in human postmortem brain tissue obtained from normal and schizophrenic persons. An autoradiographic study.

[3H]Neurotensin binding and autoradiographic techniques were used to determine the distribution and density of neurotensin receptors in normal and schizophrenic postmortem brain tissue. Coronal hemi-brain blocks of tissue were cut at the level of the caudate and hippocampus from frozen brain tissue obtained from normal individuals with no known psychiatric or neurologic illnesses and from schizophrenic subjects off- or on-antipsychotic drugs at the time of death. Each hemi-block was further divided, sectioned, thaw mounted on to slides, incubated with [3H]neurotensin and apposed to film. Digitized images were analyzed for binding densities. Areas of intense binding include the substantia nigra, the entorhinal cortex, superficial layers of the cingulate, middle frontal, and insular cortices; and with moderate binding in nucleus accumbens, and caudate. Schizophrenic patients off- (3 months or more) or on-antipsychotic drugs at the time of death were tested; all patients showed a reduced level of neurotensin receptors in the caudate (68% of normals), cingulate (34%) and prefrontal cortices (25%).

Adult↗
PubMed1998

Direct determination of dopamine D4 receptors in normal and schizophrenic postmortem brain tissue: a [3H]NGD-94-1 study.

Using an indirect subtraction binding technique and human postmortem tissue, several laboratories reported finding increases in dopamine D4 receptors in caudate nuclei of schizophrenic patients, although others have not replicated these findings. NGD-94-1 is a selective D4 antagonist with low affinity for the D2 and D3 receptors. [3H]NGD-94-1 has been used in this study to directly determine the density of D4 receptors in normals (n = 13) and schizophrenic subjects (n = 7) off antipsychotic drugs for at least 3 months prior to death, or on antipsychotic (n = 7) drugs at the time of death. Human postmortem coronal brain sections were incubated with [3H]NGD-94-1 and autoradiograms developed; and binding in pertinent regions was quantified. In normals, the highest density of [3H]NGD-94-1 binding was in the hippocampus (68 fmol mg(-1), temporal (33), insular (30), and entorhinal cortices (24.9). Significant increases in [3H]NGD-94-1 density in schizophrenics (n = 14) vs normals (n = 13) were observed in the entorhinal cortex (46%) at both low and high magnifications. The increases observed in the schizophrenics were found in both schizophrenics off antipsychotic drugs for at least 3 months prior to death and those on antipsychotic drugs at the time of death. Thus, the changes may be disease-related and not a consequence of pharmacological treatment. No significant differences were found between the two schizophrenic groups in any brain area studied.

Adult↗
PubMed1998

Weight gain in adolescents treated with risperidone and conventional antipsychotics over six months.

Weight gain is a serious side effect of antipsychotic therapy. Potential consequences of obesity include noncompliance with medications as well as significant morbidity and mortality. Because atypical antipsychotic agents are increasingly being used in adolescents, it is important to determine and further characterize the rate of weight gain in this population. This study compares weight gain associated with the use of conventional antipsychotic agents with that seen with risperidone in adolescents. This retrospective study identified 60 adolescent inpatients who were taking risperidone (n = 18), conventional neuroleptics (n = 23), or no antipsychotic medication (n = 19). Monthly height and weight measurements were recorded over a 6-month period, allowing body mass index (BMI) values to be calculated. Subjects treated with risperidone gained a mean of 8.64 kg and increased in body mass by 3.67 kg/m2 over the 6-month observation period. Those taking conventional antipsychotics gained 3.03 kg or 0.31 kg/m2 in body mass, whereas the control group actually lost weight (-1.04 kg, or -1.01 kg/m2) in the same time frame. Although both antipsychotic groups gained in weight and BMI, the risperidone-treated group gained significantly more body mass than did the conventional antipsychotic group (p = 0.0011). Gains in body weight did not correlate with dose, and concomitant medications such as stimulants and lithium did not contribute to changes in BMI.

Adolescent↗
PubMed1998

Olanzapine compared with chlorpromazine in treatment-resistant schizophrenia.

OBJECTIVE: The purpose of this study was to compare the efficacy of olanzapine with that of chlorpromazine plus benztropine in patients with treatment-resistant schizophrenia. METHOD: One hundred three previously treatment-resistant patients with schizophrenia diagnosed according to the DSM-III-R criteria were given a prospective 6-week trial of 10-40 mg/day of haloperidol. Eighty-four of them failed to respond to that trial and agreed to be randomly assigned to an 8-week fixed-dose trial of either 25 mg/day of olanzapine alone or 1200 mg/day of chlorpromazine plus 4 mg/day of benztropine mesylate. RESULTS: Fifty-nine (70%) of the 84 subjects completed the trial. The primary outcome measures were Brief Psychiatric Rating Scale total score and positive symptom score, Scale for the Assessment of Negative Symptoms global score, and Clinical Global Impression score. An analysis of variance for the subjects who completed the study showed no difference in efficacy between the two drugs. Seven percent of the olanzapine-treated patients responded according to a priori criteria; no chlorpromazine-treated patients responded. The olanzapine-treated patients had fewer motor and cardiovascular side effects than the chlorpromazine-treated patients. Extrapyramidal symptoms and akathisia were similar in the two groups, although no antiparkinsonian drugs were used in the olanzapine group. CONCLUSIONS: Olanzapine and chlorpromazine showed similar efficacy, and the total amount of improvement with either drug was modest. Olanzapine-treated patients had fewer side effects than chlorpromazine-treated patients.

Adult↗
PubMed1998

Optimizing treatment with clozapine.

Clozapine is the only antipsychotic agent that is effective in treatment-resistant schizophrenia. Despite its superior efficacy to chlorpromazine and the fact that it has fewer extrapyramidal side effects than conventional antipsychotics do, clozapine is relatively underused. This may be due in part to a lack of appreciation of clozapine's favorable risk-benefit ratio in many patients. In addition, clozapine is only indicated for use in patients who fail to respond adequately to standard antipsychotic treatment. Treatment with clozapine considerably improves psychiatric well-being and reduces readmission to the hospital and reduces family burden in many severely ill patients. However, clozapine is associated with severe side effects, including weight gain, tachycardia, sedation, seizures, and agranulocytosis. These risks must be weighed against the risks associated with schizophrenia (e.g., suicide). The death rate attributed to clozapine-induced agranulocytosis has been low, a fact that is largely attributable to safety measures such as the Clozaril National Registry. Determining the optimal dosage for each patient will maximize the benefits of treatment while reducing side effects. In some patients, monitoring plasma levels of drug may aid in optimizing treatment. The optimal plasma level of clozapine is 200 to 350 ng/mL. This usually corresponds to a daily dose of 200 to 400 mg, although dosage must be individualized. If patients improve significantly during treatment with clozapine, they should continue to be treated with clozapine and should be withdrawn from this treatment only when medically warranted. Psychotic relapse rates may be as high as 80% among patients switched from clozapine to other novel antipsychotic agents.

Antipsychotic Agents↗
PubMed1997

Benzodiazepine receptors in the post-mortem brain of suicide victims and schizophrenic subjects.

To examine the role of benzodiazepine (BZ) receptors in suicide and schizophrenia, we determined BZ receptors in post-mortem brain (Brodmann's area 10) obtained from suicide victims, schizophrenic patients, and control subjects using [3H]RO15-1788 as the radioligand. The maximum number of binding sites (Bmax) of BZ receptors in the cortex of suicide victims was significantly higher compared with controls, but this increase was mainly due to those suicide victims who died by violent means and whose Bmax was significantly higher than of those who died by non-violent means or control subjects. In schizophrenic patients, Bmax was not significantly different from that of control subjects. When the schizophrenic subjects were separated into two groups, those on neuroleptics and those off neuroleptics for at least 12 months, however, the mean Bmax of BZ receptors in the prefrontal cortex in post-mortem brain obtained from schizophrenic patients on neuroleptics was significantly lower than Bmax in drug-free schizophrenic patients or normal controls. There were no significant differences among groups in values of the apparent dissociation constant (KD) of [3H]RO15-1788 binding. These results suggest that BZ receptors are up-regulated in the cortex of suicide victims, specifically those who used violent means, and that neuroleptic treatment may result in decreased central BZ receptor binding in the cortex of schizophrenic patients. Thus, the method of suicide and previous exposure to neuroleptics should be considered in the interpretation of data on BZ receptors.

Adult↗
PubMed1997

Protein kinase C in the postmortem brain of teenage suicide victims.

Increased serotonin2A (5-HT2A) receptors have been reported in the postmortem brain of suicide victims. To examine if this increase is associated with the dysregulation of postreceptor sites in the signaling cascade, we determined [3H]phorbol dibutyrate (PDBU) binding to protein kinase C (PKC) in postmortem brain samples (Brodmann's areas 8 and 9) obtained from teenage suicide victims and control subjects. [3H]PDBU binding to PKC was determined in membranal and cytosolic fractions. We observed that Bmax of [3H]PDBU binding sites was significantly decreased in both membranal and cytosolic fractions in brain samples from Brodmann's areas 8-9 compared to matched controls. These results thus suggest that PKC may play a role in the pathophysiology of suicidal behavior.

Adolescent↗
PubMed1997

Comorbid bulimia nervosa and schizophrenia.

OBJECTIVE: Despite literature citing the frequency of abnormal eating behavior in persons with schizophrenia, little attention has been paid to the comorbidity of eating disorders and schizophrenia. This case review explores the comorbidity of bulimia nervosa and schizophrenia and its possible clinical implications. METHOD: The authors present four case reports of women with rigorously diagnosed schizophrenia who have eating-disordered behavior. RESULTS: The first case describes a woman whose bulimia nervosa clearly preceded the onset of her schizophrenia. The second and third cases describe women who have many characteristics and risk factors for bulimia nervosa and whose bulimic symptoms significantly interact with psychotic symptoms. The fourth case describes a woman with bulimic behavior which is clearly responsive to psychosis. She does not have a history and behavioral profile of true bulimia nervosa. DISCUSSION: These case reports extend support to a model that schizophrenia and bulimia may coexist in a complex, interactive fashion with important clinical implications.

Adult↗
PubMed1997

Evaluation of treatment-resistant schizophrenia.

A systematic approach to the evaluation and characterization of treatment resistance in schizophrenia has become increasingly important since the introduction of clozapine, risperidone, and olanzapine. The need for accurate evaluation will increase with the introduction of the next generation of antipsychotic medications. People with schizophrenia may manifest a poor response to therapy secondary to intolerance of medication, poor compliance, or inappropriate dosing, as well as true resistance of their illness to antipsychotic drug therapy. Clinicians facing the decision of when to change from one antipsychotic to another must clearly understand the appropriate length of a trial and what target symptoms respond to antipsychotics in order to maximize the response in patients with treatment-resistant schizophrenia.

Antipsychotic Agents↗
PubMed1997

Time to clozapine response in a standardized trial.

OBJECTIVE: The authors sought to determine the time to clozapine response in treatment-refractory patients with schizophrenia. METHOD: Antipsychotic response to a clozapine trial was examined in 50 treatment-refractory schizophrenic inpatients. Subjects were treated with clozapine for at least 12 months, regardless of response status, according to a standardized, increasing dose protocol. Behavioral changes were measured through monthly assessments with the Brief Psychiatric Rating Scale. RESULTS: Thirty-four subjects (68%) met clinical response criteria by the end of the trial. Response was achieved at a mean dose of 468 mg/day (SD = 168). The dose of 30 (88%) of the responding patients was 600 mg/day or less. The mean time to response was 82 days (SD = 100, range = 10-401). It took an average of 60 days (SD = 87) for subjects to reach the dose at which clozapine response was achieved. Once this dose was reached, the average response time was 17 days (SD = 14, range = 2-56). All 34 subjects who responded met criteria within 8 weeks of a clozapine dose escalation. No late response was found in the remaining 16 subjects despite a mean follow-up period of 75 weeks (SD = 50). CONCLUSIONS: In this study, all patients who responded to clozapine did so within 8 weeks of a change in dose. Thus, there appears to be little clinical gain in prolonging exposure to clozapine beyond 8 weeks at any particular dose if no response is seen.

Adult↗
PubMed1997

The application of neuroimaging techniques to drug development.

Neuroimaging is a powerful and innovative tool for studying the pathology of psychiatric diseases and, more recently, for studying the drugs used in their treatment. Technological advances in imaging have made it possible to noninvasively extract information from the human brain regarding a drug's mechanism and site of action. Until now, our understanding of human brain pharmacology has depended primarily on indirect assessments or models derived from animal studies. However, the advent of multiple techniques for human brain imaging allows researchers to focus directly on human pharmacology and brain function. This review outlines available neuroimaging techniques and examines how these various methods have already been applied to the drug development process, as well as how they might be applied in the future.

Antipsychotic Agents↗
PubMed1996

D2-type dopamine receptors in postmortem human brain sections from normal and schizophrenic subjects.

The density of the presumed dopamine D4 receptor ([3H]YM-09151-2 minus [3H]raclopride), as well as the densities of the two ligands themselves were compared in various areas of cerebral tissue from normal versus schizophrenic subjects off or on antipsychotic drugs at the time of death. Using autoradiographic techniques, and analyzing various brain areas, no differences were found in the density of the D4 receptor, nor were differences found between the groups, in any brain region, in the amount of bound [3H]YM-09151-2 or [3H]raclopride. There were, therefore, no differences in the density of the D3-type receptors, including the D4 receptor, in normal and schizophrenic subjects off or on antipsychotic drugs at the time of death.

Adult↗
PubMed1996

Clozapine conflict.

Explore the source record for details and available documents.

Antipsychotic Agents↗
PubMed1995

Patient response and resource management: another view of clozapine treatment of schizophrenia.

OBJECTIVE: Issues in clozapine treatment were considered in terms of implications for resource management. METHOD: A critical review of the literature on time course and pattern of response to clozapine was used to address treatment of negative symptoms, late responders, and extent of clinical benefit in ordinary settings. RESULTS: Superior efficacy of clozapine for partial and poor neuroleptic responders is observed in about one-half of the cases. Response is rapid once a therapeutic dose is reached, and the data do not support the proposition that some patients first respond only after 3-12 months of therapy. The cumulative benefit over several months of treatment and the broad range of symptoms involved in response are similar to those for typical neuroleptic drugs, suggesting that clozapine's superiority is based on greater effectiveness rather than a unique profile of treatment effects. Clozapine appears to be effective for secondary, but not primary, negative symptoms. Modal response is moderate, and extensive rehabilitation and clinical services are required to substantially enhance functional outcome. CONCLUSIONS: Many more patients merit trials with clozapine. Economic costs and adverse drug effects can be minimized by selecting patients most likely to benefit and discontinuing clozapine treatment when benefit is not observed within 2-4 months. Appropriate patients include 1) those with good responses to typical neuroleptics who experience substantial adverse effects and 2) those whose disorders respond poorly to standard neuroleptics and are defined by psychotic symptoms, thought disorder, and hostility. Treatment of primary negative symptoms is not supported by the current experimental data.

Antipsychotic Agents↗