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Biomedical subjects

Deanna L Kelly

Publications and source records attributed to Deanna L Kelly.

At least 19 recordsLinked to original sources
PubMed2006

Clozapine underutilization and discontinuation in African Americans due to leucopenia.

Clozapine use has been notably lower in African American patients than in Caucasians. It has been suggested that lower normal ranges for white blood cell (WBC) counts in African Americans, known as benign ethnic neutropenia, may account partially for the disparity. We examined the rates of leucopenia and agranulocytosis as reasons for discontinuation of clozapine in a sample of 1875 patients with schizophrenia treated in the State of Maryland. Between 1989 and 1999, 5.3% (31/588) of African Americans and 2.4% (31/1287) of Caucasians discontinued clozapine treatment due to leucopenia (chi square = 10.35, df = 1, P = 0.001). No African American patients developed agranulocytosis while 8 Caucasian patients (0.62%) developed this blood dyscrasia. Discontinuations due to leucopenia occurred throughout treatment. Discontinuations due to agranulocytosis occurred primarily in the first 18 weeks (7/8; 87.5% patients with agranulocytosis). It is likely that African Americans had clozapine discontinued unnecessarily due to benign ethnic neutropenia. We concur with recent recommendations to acknowledge differences in WBC values in African Americans and to modify prescribing guidelines or formally acknowledge benign ethnic leucopenia like in other countries in order to facilitate greater use of clozapine in these patients.

Black or African American↗
PubMed2006

Plasma concentrations of high-dose olanzapine in a double-blind crossover study.

Olanzapine is structurally similar to clozapine but has not been shown at routine doses to share the superiority of clozapine to traditional antipsychotics in treatment-resistant patients. Olanzapine, however, has been increasingly used in higher doses as clinicians attempt to find a more tolerable therapy for those refractory to conventional agents. This study examined the relationship of high-dose olanzapine plasma concentrations to symptoms, adverse effects, smoking, and gender. Thirteen patients participated in a double blind 16-week crossover study (8 weeks each arm) of olanzapine (50 mg/day) compared to clozapine (450 mg/day). Women had significantly higher plasma olanzapine levels than men at each time point in each arm (weeks 4, 6, and 8). At 8 weeks women had a steady-state olanzapine level of 278 +/- 62 ng/ml while men had a steady-state level of 127 +/- 47 ng/ml (p = 0.005). At week 4, olanzapine levels tended to be higher in those who had been on clozapine previously (205 ng/ml) compared to those who received olanzapine in the first arm (105 ng/ml). Cigarette intake was negatively correlated to olanzapine plasma concentrations (week 8: r = -0.86, p < 0.05). Plasma levels were significantly higher in those experiencing constipation (176 vs. 82 ng/ml; p = 0.022). Plasma levels of olanzapine were not associated with symptom response and anticholinergic effects were seen at greater frequency with higher olanzapine concentrations. In conclusion, this study reports plasma olanzapine levels at high fixed doses of olanzapine (50 mg/day) in relation to side effects, symptoms, smoking, and gender.

Adult↗
PubMed2006

Adjunct divalproex or lithium to clozapine in treatment-resistant schizophrenia.

This retrospective study examined adjunct divalproex (N = 15) or lithium (N = 9) in treatment-resistant schizophrenia patients added to clozapine and compared to clozapine monotherapy (N = 25). Six month total BPRS scores were similarly improved in all treatment groups, however significantly greater improvements occurred in the first month for those on divalproex (-9) or lithium (-8) vs. clozapine alone (-4.5) (F = 3.32, df = 10.43, p = 0.0003). Rates of sedation, tachycardia, orthostasis, GI disturbances, confusion and dizziness were similar among groups. Mean weight gain was 8.7 pounds for clozapine monotherapy, 3.0 pounds in the adjunct divalproex group and 13.3 pounds in the adjunct lithium group (P = NS). A trend was noted for greater increases in blood glucose levels for those treated with adjunct lithium (F = 2.62, df = 2.28, p = 0.09). The addition of divalproex was significantly more effective in reducing global symptoms (driven by hostility and anxiety) in the first month of adjunct treatment as compared to clozapine monotherapy and to previous clozapine treatment.

Adult↗
PubMed2006

Treatment considerations in women with schizophrenia.

Schizophrenia is a challenging and complex psychiatric disorder. It is a chronic disorder of thought, affect, and cognition that significantly disturbs the individual's ability to function in society and develop interpersonal relationships. The clinical presentation can be extremely varied, with symptoms including delusional thinking, disorganized thoughts and speech, hallucinatory behavior, and negative symptoms (e.g., blunted affect, avolition, alogia, anhedonia). Approximately 1% of the population is affected by schizophrenia worldwide, and women may experience different symptoms, have a later age of onset, may respond to different treatments, and may be more concerned about specific side effects than men. Women with schizophrenia traditionally have been treated in the same way as men and have generally had poorer comprehensive medical care. With the introduction of many new antipsychotic medications in recent years, this review focuses on sex differences in schizophrenia, with an emphasis on differences in treatment and side effects. Additionally, it presents patient counseling issues in sexuality and health outcomes.

Antipsychotic Agents↗
PubMed2006

Prevalence of bone mineral density loss in Korean patients with schizophrenia: a cross-sectional study.

OBJECTIVE: This study investigates bone mineral density (BMD) and the association between BMD and hormonal changes in Korean patients with schizophrenia. METHOD: This cross-sectional study was conducted from January 2005 to June 2005; 195 inpatients with schizophrenia (DSM-IV) were screened. Among them, 51 patients aged 18 to 45 years who had taken haloperidol monotherapy for at least 2 years participated in this study. The control group consisted of normal healthy volunteers who were of similar ages (N = 57). Bone mineral density was determined by a GE Lunar 4500 scanner. Hormone levels were measured by using commercial kits. The Student t test, the Pearson chi2 test, the Wilcoxon rank sum test, and logistic regression analysis were used for data analysis. RESULTS: Female patients, but not male patients, showed significantly lower BMD than the normal controls as seen in all bone regions studied. Among 18 female patients with BMD loss, 17 patients showed hyperprolactinemia, and 7 showed combined hypoestrogenemia. Prolactin levels were significantly higher in the female patients with BMD loss compared to those with normal bone density; however, other hormone levels were not different between the 2 groups. There was no significant difference in hormonal levels between bone loss and normal bone density groups. CONCLUSIONS: Bone mineral density loss in patients with schizophrenia tended to differ by gender. Decreased BMD compared to normal controls was seen in female patients; however, this was not observed in men.

Absorptiometry, Photon↗
PubMed2006

Clozapine utilization and outcomes by race in a public mental health system: 1994-2000.

OBJECTIVE: This study aimed to assess racial differences in clozapine prescribing, dosing, symptom presentation and response, and hospitalization status. This study extends previous studies of clozapine by examining patient- and treatment-related factors that may help explain or eliminate reasons for differential prescribing. METHOD: Clozapine records for 373 white and African American patients with schizophrenia or schizoaffective disorder treated between March 1, 1994, and December 31, 2000, in inpatient mental health facilities in the state of Maryland were examined. Records for this study were derived from 3 state of Maryland databases: the Clozapine Authorization and Monitoring Program, the State of Maryland Antipsychotic Database, and the Health Maintenance Information System Database. RESULTS: A total of 10.3% of African Americans (150/1458) with schizophrenia received clozapine treatment compared with 15.3% of whites (223/1453) (chi2 = 16.74, df = 1, p < .001) during inpatient treatment in the public mental health system in Maryland. Clozapine doses were lower in African Americans relative to whites (385.3 +/- 200.6 vs. 447.3 +/- 230.3 mg/day) (t = -2.66, df = 366, p = .008). At the time of clozapine initiation, whites had more activating symptoms as measured by the Brief Psychiatric Rating Scale (BPRS) (t = -3.98, df = 301, p < .0001); however, African Americans had significantly greater improvements in BPRS total symptoms (F = 4.80, df = 301, p = .03) and in anxiety/ depressive symptoms during 1 year of treatment with clozapine (F = 10.04, df = 303, p = .002). The estimated rate of hospital discharge was not significantly different for African Americans compared to whites prescribed clozapine (log-rank chi2 = 0.523, df = 1, p = .470); however, African Americans were more likely than whites to discontinue clozapine during hospitalization (log-rank chi2 = 4.19, df = 1, p = .041). CONCLUSION: Our data suggest underutilization of clozapine in African American populations. This racial disparity in clozapine treatment is of special concern because of the favorable outcomes associated with clozapine in treatment-resistant schizophrenia and in the specific benefits observed in African American patients. More research is needed to determine why disparities with clozapine treatment occur and why African Americans may be discontinued from clozapine at a higher rate, despite potential indicators of equal or greater effectiveness among African Americans compared with whites.

Black or African American↗
PubMed2005

A randomized double-blind 12-week study of quetiapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia.

Sexual dysfunction is common in people suffering from schizophrenia and is reported by patients to be a significant reason for medication nonadherence. This report contains data for 27 people with schizophrenia who participated in a randomized double-blind 12-week trial of risperidone (4 mg/day), quetiapine (400 mg/day) or fluphenazine (12.5 mg/day). At baseline and endpoint, subjects were rated on the Changes in Sexual Function Questionnaire (CSFQ), the Prolactin-Related Adverse Event Questionnaire (PRAEQ) and had prolactin levels drawn. Endpoint prolactin levels were 50.6 +/- 40.4, 24.4 +/- 18.5, and 8.2 +/- 4.4 mg/dl for risperidone (N = 12), fluphenazine (N = 9) and quetiapine (N=6), respectively (F = 7.5,df = 2, p = 0.005, controlling for sex). Orgasm quality/ability improved significantly for quetiapine as compared to fluphenazine and risperidone (F = 4.41, df = 2, p = 0.033). Seventy-eight percent of patients on fluphenazine reported sexual dysfunction whereas did only 42 and 50% of those on risperidone and quetiapine. Forty percent of quetiapine patients reported they felt better about their sexuality as compared to previous treatment, as did 55% on risperidone. Conversely, only 13% of fluphenazine subjects reported any improvement. Hormonal problems (menstrual problems, gynecomastia, galactorrhea) were predominately observed in risperidone-treated subjects. Overall, quetiapine was associated with a normalization of prolactin levels and had the greatest benefits among these drugs regarding sexual functioning.

Adult↗
PubMed2005

Comparison of clozapine use in Maryland and in Victoria, Australia.

OBJECTIVE: Studies of how differences in systems of care, including cultural differences, affect prescribing practice and patient outcomes are important and can help answer questions such as the effectiveness of clozapine in routine practice. This study examined the use of clozapine in Maryland and in Victoria, Australia. METHODS: This study used medical record data to examine the use of clozapine in January 2000 for people with schizophrenia in two different countries. Data were gathered from all six public inpatient facilities in Maryland and from the two main community outpatient centers in Victoria. Outpatients were studied in Victoria because Australia's inpatient mental health facilities have closed and people with treatment-resistant schizophrenia are managed exclusively as outpatients. RESULTS: In Maryland 591 inpatients with schizophrenia were given a prescription for second-generation antipsychotics; in Victoria 356 outpatients with schizophrenia were given such a prescription. Among second-generation antipsychotics, clozapine was used significantly more frequently in Australia than in Maryland for the treatment of schizophrenia (173 prescriptions, or 49 percent, compared with 144 prescriptions, or 19 percent). Both systems used clozapine mostly for the treatment of schizophrenia (94 percent in Victoria compared with 88 percent in Maryland). The mean clozapine dosages that were used for the treatment of schizophrenia were significantly higher in Maryland than in Australia (522 mg per day compared with 431 mg per day). CONCLUSIONS: Significant differences in use and dosages of clozapine were found in two populations that were similar in diagnoses and demographic characteristics.

Adult↗
PubMed2005

Tardive dyskinesia predicts prolactin response to buspirone challenge in people with schizophrenia.

Prolactin response to buspirone was evaluated in patients with schizophrenia, with and without tardive dyskinesia (TD). Prolactin response in patients with schizophrenia without TD was significantly decreased, compared to healthy comparison subjects (F = 6.36, df = 5, p < 0.0001). Furthermore, prolactin levels after administration of buspirone were not significantly increased from baseline. In contrast, there was no prolactin response difference between patients with schizophrenia and TD and healthy subjects. This finding suggests that decreased dopamine (D(2)) receptor sensitivity may result in lower risk of developing TD and may lead to a fuller understanding of the variable expression of D(2)-receptor mediated side effects.

Adult↗
PubMed2005

First-episode schizophrenia: a focus on pharmacological treatment and safety considerations.

Schizophrenia is a debilitating disorder, which is usually chronic, and is one of the most devastating medical illnesses. Early and appropriate treatment with antipsychotics is an important strategy for patients with first-episode schizophrenia. However, there are many possible safety issues for patients with schizophrenia that should be considered and properly addressed. Depressive symptoms and suicidal behaviour commonly occur in first-episode schizophrenic patients, and every effort should be made to treat and minimise these symptoms. There are also important issues and considerations in young and first-episode patients that should also be considered in the emergency treatment setting and for minimising medication nonadherence in this population. Most importantly, adverse effects should be considered, minimised and addressed. While first- and second-generation antipsychotics (SGAs) both appear to offer similar efficacy for amelioration of positive symptoms in first-episode patients, SGAs may offer better tolerability, specifically regarding extrapyramidal symptoms (EPS) and tardive dyskinesia risk, and some prolactin-sparing benefits. However, these medications do cause a host of adverse effects, including weight gain, metabolic disturbances, corrected QT interval prolongation and prolactin-related adverse effects, which are important considerations relating to both the short- and long-term safety of patients with schizophrenia being treated with SGAs. Clozapine and olanzapine are most likely to cause weight gain and metabolic effects, while risperidone is more likely to cause EPS and prolactin elevations. Most antipsychotics should be used in low doses to minimise adverse effects and each medication should be optimised in a highly individualised way to maximise adherence and treatment outcomes and minimise tolerability and safety concerns. At some point in their lives, these patients will most probably experience periods of depression, suicidal behaviours, adverse effects and nonadherence, and every effort should be made to minimise or prevent these from occurring. Thus, safety concerns in this group of young patients, in the beginning of their first psychotic episode, are a major issue as they are starting a journey of antipsychotic treatment that is likely to last for the remainder of their lives.

Age of Onset↗
PubMed2005

Thyroid function in treatment-resistant schizophrenia patients treated with quetiapine, risperidone, or fluphenazine.

BACKGROUND: Thyroid dysfunction is relatively common in patients with schizophrenia, possibly related to a genetic linkage of the disorders and to antipsychotic treatment. Quetiapine has been implicated as causing some degree of thyroid function changes, yet it remains unclear as to what extent or why these changes may occur. Furthermore, the need for thyroid function monitoring in patients taking this medication is not definitive. METHOD: Thyroid function was assessed in 38 adult DSM-IV-diagnosed schizophrenia patients after 6 weeks of prospective, double-blind, randomized treatment with quetiapine (400 mg/day), risperidone (4 mg/day), or fluphenazine (12.5 mg/day). Data were collected from 1997 to 2002. RESULTS: At baseline, the percentages of randomized patients with abnormal values were 18% (4/22) for serum T(3) resin uptake, 13% (4/30) for thyroid-stimulating hormone (TSH), and 9% (2/22) for total serum thyroxine (TT(4)), representing fairly widespread thyroid abnormalities independent of treatment group. Little change was noted in thyroid function during the 6 weeks of treatment, except for a significant decrease in TT(4) values for those taking quetiapine (p = .01). Clinically, however, no patients demonstrated any signs or symptoms of hypothyroidism during the study, nor were any significant changes in the free thyroxine index or TSH levels noted. CONCLUSIONS: It is expected that TT(4) levels will decrease during quetiapine treatment, and this may possibly be related to competitive metabolism of thyroid hormones and quetiapine by UDP-glucuronosyltransferase. Routine monitoring of thyroid function in quetiapine-treated patients without a history of thyroid disease is not recommended.

Adult↗
PubMed2005

Second-generation antipsychotics for schizophrenia: a review of clinical pharmacology and medication-associated side effects.

Second-generation antipsychotics (SGAs) are replacing traditional antipsychotics as first line therapy for the treatment of schizophrenia. While recent evidence suggests similar efficacy with low dose conventional antipsychotics, much of the advantage favoring SGAs comes from the fact that there are fewer extrapyramidal side effects (EPS) at effective doses with these drugs. As a medication class and with the exception of clozapine, the SGAs overall are very similar with regard to efficacy yet are heterogeneous with regard to receptor binding and structure-activity as well as their side effect liabilities. This paper will review the clinical psychopharmacology of the SGAs as well as adverse events associated with these drugs. Because certain side effects may be associated with nonadherence with treatment, more detailed data for each of the SGA with regards to EPS, weight gain and metabolic abnormalities and sexual dysfunction are presented.

Antipsychotic Agents↗
PubMed2004

Atypical antipsychotic use in a state hospital inpatient adolescent population.

Atypical antipsychotics are now the most commonly prescribed antipsychotics in young patients. These drugs are increasingly being used because of better tolerance and safety as seen in the adult populations. Youth with more severe psychopathology who are treated in the inpatient setting have been overlooked in much of the published research, and the extent of use and rationale in this population is unknown. This naturalistic retrospective study examined a population of adolescents in an inpatient state hospital setting with regard to their use of atypical antipsychotics. All patients who received an inpatient prescription for atypical antipsychotics between January 1, 1997 and June 1, 2000 and were ages 18 or younger at the time of medication initiation were included in the study. Twenty-three percent (88/380) of patients received an atypical antipsychotic: 68% (60/88) risperidone, 27% (24/88) olanzapine, and 5% (4/88) quetiapine. Psychotic disorders were considered as the primary diagnosis in only 17% of patients treated with atypical antipsychotics, and no particular diagnosis was predictive of monotherapy with an atypical antipsychotic. In the adolescent populations, atypical antipsychotics are being used for a wide variety of diagnoses and are commonly used adjunctively (more than 80%) with many concomitant psychotropic medications. More research is needed to develop useful and specific practice guidelines in children and adolescents for these commonly used medications.

Adolescent↗
PubMed2004

Sexuality and schizophrenia: a review.

Sexual functioning has received little attention as an important aspect of patient care for those suffering from severe mental disorders such as schizophrenia. Yet, it has been implicated as one of the major factors contributing to noncompliance with antipsychotic medications and is documented by people with schizophrenia to be one of the areas of treatment with the most unmet needs. A stronger focus on sexuality and preventing sexual dysfunction in schizophrenia would likely be a major benefit for improving treatment. This review will describe possible mechanisms for sexual dysfunction, describe sexual disturbances that have been documented in the literature of people who have schizophrenia, and summarize and discuss assessment measures available. Moreover, a focus on second-generation antipsychotics (SGA) and their association with sexual functioning is described. Each SGA (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) will be described for its prolactin effects, documented sexual disturbances associated with use, and product labeling regarding sexual function. Treatment options and psychosocial issues pertaining to sexuality also are presented.

Amenorrhea↗
PubMed2004

The effects of clozapine and high-dose olanzapine on brain function in treatment-resistant schizophrenia: a case study.

Although demonstrating superior efficacy in people with treatment-resistant schizophrenia, clozapine may cause serious side effects, requires blood monitoring and is costly to administer. Olanzapine is similar to clozapine in molecular structure and pharmacologic action but has not demonstrated as robust results as clozapine at routine doses (10-25 mg). Here we present a case study measuring blood flow by positron emission tomography (PET) imaging for a patient treated sequentially with a high dose of olanzapine (50 mg/day) followed by clozapine each for 8 weeks in a double-blind design. During a task, clozapine produced more brain activation patterns than during treatment with olanzapine or during the drug free condition (2 week washout). Clozapine resulted in recruitment of frontal, parietal and cingulate regions that did not appear to be active during olanzapine in this 44 year old right handed male. Additionally, a more robust decrease in symptoms was noted on the Brief Psychiatric Rating Scale (BPRS) score than with olanzapine treatment. These findings suggest that high doses of olanzapine do not produce similar brain activation patterns as clozapine in people with treatment-resistant schizophrenia.

Adult↗