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BACKGROUND: Clozapine is an effective antipsychotic for treatment-resistant schizophrenia. One limitation of clozapine use is required monitoring of absolute neutrophil count (ANC) because of the risk of clozapine-induced neutropenia. Standard monitoring requires venous blood draws, which is a significant barrier to clozapine use. METHODS: This study assesses the feasibility of use and physician and patient satisfaction of a novel point-of-care (POC) measure of ANC using Athelas One, a device that calculates white blood cell count and ANC using a fingerstick blood sample. This is a subanalysis of a prospective, open-label clinical trial of clozapine treatment, during which patients received a venous blood draw and a capillary fingerstick at baseline and Week 2 of the study, and completed a 5-point Likert scale, comparing the 2 methods. RESULTS: Patients reported benefits from the fingerstick technology, including POC testing being important for their doctors and their health, improved treatment, avoiding sending blood away, and convenience. There was a trend for less concern about the effects of blood draws on health with a fingerstick, and greater physician satisfaction with POC sampling. CONCLUSIONS: This study suggests the feasibility, satisfaction, and ease by both clinicians and patients of using POC testing for ANC monitoring during clozapine treatment.
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Antipsicóticos , Clozapina , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Estudos de Viabilidade , Humanos , Contagem de Leucócitos , Neutrófilos , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Satisfação Pessoal , Sistemas Automatizados de Assistência Junto ao Leito , Estudos ProspectivosRESUMO
Early detection and prevention of psychosis has become an international priority. Much of this work has focused on youth presenting with attenuated symptoms of psychosis-those at Clinical High Risk for psychosis (CHR)-given their elevated probability of developing the full disorder in subsequent years. Individuals at CHR may be prone to exacerbated psychological distress during the COVID-19 pandemic and its subsequent physical isolation measures, due to heightened stress sensitivity and comorbid mental health problems. Telepsychotherapy holds promise for reaching this population, especially during the current COVID-19 outbreak. However, there are limited evidence-based guidelines or interventions for use of telepsychotherapy with this population. In this paper, we review common clinical issues for individuals at CHR and how they might be exacerbated by the COVID-19 pandemic; best practices for treatment and adaptations for telepsychotherapy for individuals at CHR; and highlight real clinical issues that we are currently experiencing in a United States-based specialized CHR clinic as we conduct telepsychotherapy via videoconferencing. We conclude with questions for those in the field to contemplate, as well as potential challenges and benefits in using telepsychotherapy with individuals at CHR and their families.
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Background: Approximately one-third of people with schizophrenia have elevated levels of anti-gliadin antibodies of the immunoglobulin G type (AGA IgG) a higher rate than seen in healthy controls. We performed the first double-blind clinical trial of gluten-free versus gluten-containing diets in a subset of patients with schizophrenia who were positive for AGA IgG. Methods: In this pilot feasibility study, 16 participants with schizophrenia or schizoaffective disorder who had elevated AGA IgG (≥ 20 U) but were negative for celiac disease were admitted to an inpatient unit for a 5-week trial. All participants received standardized gluten-free meals and were randomized in a double-blind fashion to receive a shake containing 10 g of gluten flour or 10 g of rice flour each day. Participants were rated for psychiatric, cognitive and gastrointestinal symptoms at baseline and endpoint. Results: Of the 16 participants, 14 completed the 5-week trial (2 discontinued early for administrative reasons). Compared with participants on the gluten-containing diet, participants on the gluten-free diet showed improvement on the Clinical Global Impressions scale (Cohen d = 0.75) and in negative symptoms (Cohen d = 0.53). We noted no improvement in positive or global cognitive symptoms, but did observe an improvement in attention favouring the gluten-free diet (Cohen d = 0.60). Robust improvements in gastrointestinal adverse effects occurred in the gluten-free group relative to the glutencontaining group. Adverse effects were similar between groups. Limitations: This study was limited by its small sample size; larger studies are needed. Conclusion: This feasibility study suggests that removal of gluten from the diet is associated with improvement in psychiatric and gastrointestinal symptoms in people with schizophrenia or schizoaffective disorder.
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Gliadina/imunologia , Transtornos Psicóticos/dietoterapia , Transtornos Psicóticos/imunologia , Esquizofrenia/dietoterapia , Esquizofrenia/imunologia , Adulto , Anticorpos/imunologia , Dieta Livre de Glúten , Método Duplo-Cego , Estudos de Viabilidade , Feminino , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Projetos PilotoRESUMO
To estimate 20-year mortality risk in people with schizophrenia treated with second-generation antipsychotics (SGA) and examine the effects of cigarette smoking on mortality. Of the 1199 individuals with schizophrenia in the study, estimated 20-year all-cause mortality risk by Kaplan Meier Curve was 30% and leading causes of death included 27% cardiovascular disease, 13% cancer, 12% non-HIV infection, 5% respiratory causes, 20% other causes and 18% had unknown cause of death. For all-cause mortality, we found that white race and male sex were significant risk factors (HR = 1.5, p = 0.002 and HR = 1.33, p = 0.033, respectively). For cardiovascular mortality risk, we showed that cigarette smokers and white race were at higher risk (HR = 1.86, p = 0.017 and HR = 1.71, p = 0.045, respectively). Cardiovascular mortality risk at 20-years is 11%. Kaplan-Meier Survival Curve showed a statistical difference for smokers and non-smokers in cardiovascular mortality over the 20-year follow-up (Log rank chi-square = 5.35, df = 1, p = 0.02). 20-year all-cause mortality risk for individuals with schizophrenia was found to be 30% with cardiovascular disease as a leading cause. Cigarette smokers and white race were associated with an increased risk of death. Regarding cardiovascular mortality specifically, cigarette smoking increased risk by 86% over a 20-year period. Clozapine was neither a risk factor for all-neither cause nor cardiovascular mortality. This data suggests that long-term cardiovascular mortality continues to be increased in schizophrenia for those who are or have been cigarette smokers.
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Antipsicóticos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/mortalidade , Fumar Cigarros/efeitos adversos , Clozapina/efeitos adversos , Esquizofrenia/tratamento farmacológico , Adulto , Idoso , Causas de Morte , Comorbidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE/BACKGROUND: Prolactin-related adverse effects contribute to nonadherence and adverse health consequences, particularly in women with severe mental illness. Treating these adverse effects may improve treatment acceptability, adherence, and long-term outcomes. METHODS/PROCEDURES: Premenopausal women with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder were recruited for a randomized, double-blind, placebo-controlled 16-week trial of adjunct aripiprazole (5-15 mg/d). Participants had elevated prolactin (>24 ng/mL) and were experiencing galactorrhea, amenorrhea, oligomenorrhea, or sexual dysfunction on a prolactin-elevating antipsychotic. Participants were evaluated biweekly for prolactin elevation and galactorrhea and completed a menstrual diary review. Psychiatric symptoms and adverse effects were closely monitored. FINDINGS/RESULTS: Forty-six women were randomized (n = 25 aripiprazole, n = 21 placebo). Thirty-seven completed at least 8 weeks of the study (n = 20 [80%] aripiprazole and n = 17 [81%] placebo). Aripiprazole (mean dose, 11.7 ± 2.4 mg/d) was effective for lowering prolactin relative to placebo (P = 0.04). In addition, 45% (9/20) of the aripiprazole group had a normalized prolactin (<24 mg/mL) compared with 12% (2/17) of the placebo group (P = 0.028). Galactorrhea resolved in 77% (10/13) of the aripiprazole-treated participants compared with 33% (4/12) in the placebo group (P = 0.028). Normalization of sexual function (<16 on the Arizona Sexual Experience Scale) occurred in 50% on aripiprazole (7/14) versus 9% (1/11) on placebo (P = 0.030). No differences between groups in symptoms or adverse effects were noted. Overall, women rated a mean score of 4.6 ± 0.6 on a 5-point Likert scale for sexual function improvement, suggesting their particular satisfaction with improvement in this domain. IMPLICATIONS/CONCLUSIONS: Building upon prior studies, this rigorous evaluation confirms the utility of adjunctive aripiprazole as a strategy for improving prolactin and managing prolactin-related adverse effects in premenopausal women with psychosis.
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Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Quimioterapia Combinada/métodos , Pré-Menopausa/efeitos dos fármacos , Prolactina/sangue , Transtornos Psicóticos/tratamento farmacológico , Adulto , Amenorreia/induzido quimicamente , Amenorreia/prevenção & controle , Antipsicóticos/efeitos adversos , Aripiprazol/administração & dosagem , Método Duplo-Cego , Feminino , Galactorreia/induzido quimicamente , Galactorreia/prevenção & controle , Humanos , Adesão à Medicação , Oligomenorreia/induzido quimicamente , Oligomenorreia/prevenção & controle , Qualidade de VidaRESUMO
Recent literature suggests that schizophrenia is linked to an abnormal response of the immune system. Interferon-γ is a cytokine that acts as a mediator between immune stimulation and the kynurenine pathway and may be related to cognitive abilities. The objectives of the present study are to determine if serum cytokines are correlated with cognitive function differently in patients with schizophrenia compared to controls. Fourteen midlife (30-70 year-old) females with DSM-IV diagnosis of schizophrenia or schizoaffective disorder and 13 midlife control females were analyzed. Cytokines were collected from serum blood draws and analyzed at the Cytokine Core Lab at the University of Maryland, Baltimore. The RBANS, HVLT-R, and UPSA were performed to measure cognition and social performance. The results demonstrate a non-significant difference between interferon-γ levels in women with schizophrenia compared to controls, but this cytokine appears to correlate to cognitive abilities differently in these groups. There were several significant negative correlations between interferon-γ and cognition in midlife patients with schizophrenia, but only one in the midlife control group. The negative correlations between interferon-γ and cognition in patients with schizophrenia suggest the hypothesis that inflammation and the kynurenine pathway have important roles in this disorder.
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Cognição/fisiologia , Disfunção Cognitiva , Citocinas/sangue , Inflamação , Interferon gama/sangue , Transtornos Psicóticos , Esquizofrenia , Adulto , Fatores Etários , Idoso , Disfunção Cognitiva/sangue , Disfunção Cognitiva/imunologia , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Pessoa de Meia-Idade , Transtornos Psicóticos/sangue , Transtornos Psicóticos/imunologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/sangue , Esquizofrenia/imunologia , Esquizofrenia/fisiopatologiaRESUMO
Clozapine is the sole antipsychotic agent effective for the treatment of refractory schizophrenia. Sixty percent of clozapine-treated patients, however, fail to adequately respond. Minocycline, a tetracycline antibiotic, possesses antiinflammatory and neuroprotective properties that may play a role in schizophrenia. Clozapine is mainly metabolized by CYP1A2 enzymes, and minocycline may potentially inhibit CYP1A2 as hypothesized by case report data. To date, no pharmacokinetic interaction has been reported between minocycline and clozapine. This is a secondary analysis of a 10-week controlled study of adjunctive minocycline to clozapine in treatment refractory schizophrenia. Clozapine plasma levels were collected every two weeks during the study. 28 participants assigned to receive minocycline and 22 assigned to placebo were included. No differences existed in baseline demographics, clozapine dose or plasma levels. Average changes from baseline in clozapine plasma level (p = 0.033) were significantly higher in the minocycline group despite maintenance of stable doses. No statistically significant treatment differences were found in the norclozapine (p = 0.754) or total clozapine (p = 0.053) changes in plasma levels, although possible changes in total clozapine levels require further investigation. This analysis suggests that minocycline administration may lead to increased clozapine plasma levels. Further study is needed to examine possible explanations.
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Antipsicóticos/sangue , Clozapina/sangue , Minociclina/farmacologia , Fármacos Neuroprotetores/farmacologia , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Clozapina/análogos & derivados , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minociclina/administração & dosagem , Fármacos Neuroprotetores/administração & dosagemRESUMO
OBJECTIVE: This study sought to examine the predictors of health risk perception in smokers with or without schizophrenia. METHODS: The health risk subscale from the Smoking Consequences Questionnaire was dichotomized and used to measure health risk perception in smokers with (n = 67) and without schizophrenia (n = 100). A backward stepwise logistic regression was conducted using variables associated at the bivariate level to determine multivariate predictors. RESULTS: Overall, 62.5% of smokers without schizophrenia and 40.3% of smokers with schizophrenia completely recognize the health risks of smoking (p ≤ .01). Multivariate predictors for smokers without schizophrenia included: sex (Exp (B) = .3; p < .05), Smoking Consequences Questionnaire state enhancement (Exp (B) = .69; p < .01), and craving relief (Exp (B) = 1.8; p < .01). Among smokers with schizophrenia, predictors were education (Exp (B) = .7; p < .05), nicotine dependence (Exp (B) = .5; p < .01), motivation to quit (Exp (B) = 1.8; p < .01), and Smoking Consequences Questionnaire craving relief (Exp (B) = 1.8; p < .01). CONCLUSIONS: There was overlap and differences between predictors in smokers with and without schizophrenia. Commonly used techniques for education on the health consequences of cigarettes may work in smokers with schizophrenia, but intervention efforts specifically tailored to smokers with schizophrenia might be more efficacious.
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Atitude Frente a Saúde , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Fumar/psicologia , Tabagismo/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Tabagismo/complicaçõesRESUMO
OBJECTIVE: Nicotine dependence is high in schizophrenia, and craving is known to impact relapse during quit attempts. METHODS: We compared tobacco craving in smokers with schizophrenia treated with different antipsychotics. RESULTS: Mean craving scores were lowest in participants receiving first-generation antipsychotics, although these differences were not statistically significant. Craving with clozapine was not lower than with other antipsychotics. CONCLUSIONS: Further research is needed to determine whether differences in craving exist between antipsychotic classes.
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Antipsicóticos/uso terapêutico , Fissura/efeitos dos fármacos , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Fumar/psicologia , Tabagismo/psicologia , Adulto , Benzodiazepinas/uso terapêutico , Clozapina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Tabagismo/complicaçõesAssuntos
Autoanticorpos/sangue , Citocinas/sangue , Dieta Livre de Glúten , Ácido Cinurênico/sangue , Esquizofrenia/sangue , Triptofano/sangue , Adolescente , Adulto , Biomarcadores/sangue , Dieta Livre de Glúten/efeitos adversos , Método Duplo-Cego , Feminino , Gliadina/imunologia , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Transdução de Sinais , Adulto JovemRESUMO
OBJECTIVE: Clozapine is the most effective antipsychotic for treatment refractory people with schizophrenia, yet many patients only partially respond. Accumulating preclinical and clinical data suggest benefits with minocycline. We tested adjunct minocycline to clozapine in a 10-week, double-blind, placebo-controlled trial. Primary outcomes tested were positive, and cognitive symptoms, while avolition, anxiety/depression, and negative symptoms were secondary outcomes. METHODS: Schizophrenia and schizoaffective participants (n = 52) with persistent positive symptoms were randomized to receive adjunct minocycline (100 mg oral capsule twice daily; n = 29) or placebo (n = 23). RESULTS: Brief Psychiatric Rating Scale (BPRS) psychosis factor (P = 0.098; effect size [ES], 0.39) and BPRS total score (P = 0.075; ES, 0.55) were not significant. A change in total BPRS symptoms of more than or equal to 30% was observed in 7 (25%) of 28 among minocycline and 1 (4%) of 23 among placebo participants, respectively (P = 0.044). Global cognitive function (MATRICS Consensus Cognitive Battery) did not differ, although there was a significant variation in size of treatment effects among cognitive domains (P = 0.03), with significant improvement in working memory favoring minocycline (P = 0.023; ES, 0.41). The Scale for the Assessment of Negative Symptoms total score did not differ, but significant improvement in avolition with minocycline was noted (P = 0.012; ES, 0.34). Significant improvement in the BPRS anxiety/depression factor was observed with minocycline (P = 0.028; ES, 0.49). Minocycline was well tolerated with significantly fewer headaches and constipation compared with placebo. CONCLUSIONS: Minocycline's effect on the MATRICS Consensus Cognitive Battery composite score and positive symptoms were not statistically significant. Significant improvements with minocycline were seen in working memory, avolition, and anxiety/depressive symptoms in a chronic population with persistent symptoms. Larger studies are needed to validate these findings.
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Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Minociclina/administração & dosagem , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The Patient Protection and Affordable Care Act focuses on improving consumer engagement and patient-centered care. This article describes the design and rationale of a study targeting family engagement in pediatric mental health services. The study is a 90-day randomized trial of a telephone-delivered Family Navigator services versus usual care for parents of Medicaid-insured youth younger than 13 years with serious mental illness. Youth are identified through a pediatric antipsychotic medication preauthorization program. Family Navigators offer peer support to empower and engage parents in their child's recovery. Outcomes include parent report of empowerment, social support, satisfaction with child mental health services, and child functioning as well as claims-based measures of psychotherapy service utilization and antipsychotic medication dosage. The focus on "family-centered" care in this study is strongly supported by the active role of consumers in study design and implementation.
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Prolactin elevations occur in people treated with antipsychotic medications and are often much higher in women than in men. Hyperprolactinemia is known to cause amenorrhea, oligomenorrhea, galactorrhea and gynecomastia in females and is also associated with sexual dysfunction and bone loss. These side effects increase risk of antipsychotic nonadherence and suicide and pose significant problems in the long term management of women with schizophrenia. In this manuscript, we review the literature on prolactin; its physiology, plasma levels, side effects and strategies for treatment. We also present the rationale and protocol for an ongoing clinical trial to treat symptomatic hyperprolactinemia in premenopausal women with schizophrenia. More attention and focus are needed to address these significant side effects and help the field better personalize the treatment of women with schizophrenia.
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Antipsicóticos/efeitos adversos , Agonistas de Dopamina/uso terapêutico , Hiperprolactinemia/tratamento farmacológico , Piperazinas/uso terapêutico , Quinolonas/uso terapêutico , Esquizofrenia/complicações , Adulto , Antipsicóticos/uso terapêutico , Aripiprazol , Protocolos Clínicos , Feminino , Humanos , Hiperprolactinemia/sangue , Hiperprolactinemia/induzido quimicamente , Hiperprolactinemia/complicações , Projetos de Pesquisa , Esquizofrenia/tratamento farmacológicoRESUMO
INTRODUCTION: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but it is markedly underutilized, particularly in the US Black population, partly because of concern over clozapine-associated low absolute neutrophil count (ANC). People of African descent have a lower normative ANC range than the White population, which is associated with a specific "ACKR1-null" ("Duffy null") CC genotype (SNP rs2814778) on the ACKR1 gene, termed benign ethnic neutropenia (BEN). The range of ANC variability and safety of clozapine have not been established in people with BEN or examined prospectively in people of African descent. METHODS: We completed a multisite, 6-month, prospective, open-label clinical trial of clozapine treatment in people of African descent with schizophrenia spectrum disorders for whom clozapine was clinically indicated, with or without the ACKR1-null genotype. We examined clozapine safety and weekly ANC during clozapine treatment and evaluated ANC variability by ACKR1-null genotype, sex, study site, and clozapine dosing using repeated measures analysis of covariance. Genotype was assayed using TaqMan® technology. RESULTS: We enrolled 274 participants, of whom 227 (82.8 %) completed 6 months of clozapine treatment. There was one case of severe neutropenia (<500 cells/mm3) (0.36 %) over 1467.6 person-months of clozapine exposure. This participant recovered without sequelae after discontinuation of clozapine. Of the 249 participants with known genotypes, 199 (79.9 %) had the ACKR1-null genotype. Neutropenia (<1500 cells/mm3) occurred significantly more often in the ACKR1-null group (33 % [65/199]) than in those with the T allele (6 % (3/50); p < 0.001). Fourteen (5 %) patients discontinued due to adverse events. Rates of infection and fever were low and sialorrhea was the commonest side effect (N = 187, 68 %). CONCLUSION: To our knowledge, this is the largest prospective clozapine trial in people of African descent. Severe neutropenia was rare, despite the high prevalence (80 %) of the ACKR1-null genotype. Our findings suggest that clozapine can be used safely in Black patients including those with BEN.
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OBJECTIVE: Treatment of schizophrenia in patients with comorbid substance use (alcohol/illicit drug use, abuse or dependence) presents challenges for public health systems. Substance use in people with schizophrenia is up to four times greater than the general population and is associated with medication nonadherence and poor outcomes. Therefore, continuous antipsychotic treatment in this population may pose more of a challenge than for those with schizophrenia alone. Many clinical trials and treatment recommendations in schizophrenia do not take into consideration substance use as people with comorbid substance use have typically been excluded from most antipsychotic trials. Nonetheless, antipsychotic treatment appears to be as efficacious in this population, although treatment discontinuation remains high. The objective of this review was to highlight the importance and utility of considering long-acting injectable antipsychotics for patients with schizophrenia and comorbid substance use. METHODS: We did a literature search using PubMed with key words schizophrenia and substance use/abuse/dependence, nonadherence, antipsychotics, long acting injectables, relapse, and psychosocial interventions. We limited our search to human studies published in English and 4,971 articles were identified. We focused on clinical trials, case reports, case series, reviews and meta-analyses resulting in 125 articles from 1975-2011. RESULTS: Our review suggests the potential role of long-acting injectables for people with comorbid substance use and schizophrenia in leading to improvements in psychopathology, relapse prevention, fewer rehospitalizations, and better outcomes. CONCLUSIONS: While more research is needed, long-acting antipsychotics should be considered an important option in the management of people with schizophrenia and comorbid substance use.
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INTRODUCTION: Patients with severe mental illness are falsely characterized as aggressive by the media, perpetuating stigma. While exaggerated, some patients with severe mental illness are more aggressive without treatment. Clozapine may have a unique anti-aggressive effect in patients with schizophrenia-related disorders, independent of antipsychotic or sedative effects. Limited data in forensic and involuntary committed patients is currently available. PURPOSE: This study evaluates clozapine's effects on hostility and aggression in court-ordered Black patients. METHODS: This study analyzes a subgroup of Black patients from a larger prospective 24-week open-label clozapine study. All patients were involuntarily committed and enrolled from two participating state psychiatric hospitals. The primary outcome measured was total use of 'as needed' (PRN) or 'immediate need' (STAT) medications for aggression/hostility. Secondary outcomes included number and duration of seclusion and restraint (S/R) episodes, and changes in Brief Psychiatric Rating Scale (BPRS) hostility factor score. RESULTS: Sixty-nine patients were included in our analysis. Significant reductions were noted in PRN/STAT medication use over time (χ2 = 6.90; p = 0.008) and the BPRS hostility factor score was reduced by 30% over the 24 weeks (F = 4.34, df = 62, p = 0.002). CONCLUSIONS: Treatment with clozapine effectively reduced hostility and aggression within this cohort of involuntarily committed Black patients with mental illness compared to baseline. Specifically, it helped lower the total number of PRN/STAT medication administrations and improved clinician-rated hostility factor scores on the BPRS. Our findings are pertinent as data in forensic settings is lacking and Black patients have been infrequently included in large prospective clinical trials with clozapine. GOV IDENTIFIER: NCT02404155.
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Antipsicóticos , Clozapina , Esquizofrenia , Agressão , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Clozapina/farmacologia , Clozapina/uso terapêutico , Humanos , Estudos Prospectivos , Esquizofrenia/tratamento farmacológicoRESUMO
Schizophrenia is a severe mental disorder with various medical comorbidities and early mortality. Hyperprolactinemia is common in women and its impact on sexual function, galactorrhea and amenorrhea is well known. This paper evaluates the risk of 25-hydroxy vitamin D deficiency and other metabolic related laboratory abnormalities in women with schizophrenia having hyperprolactinemia (N = 43). The mean prolactin level in these women was 88.5 ± 56.0 ng/mL. We found that 100% of women were overweight of which 74% (32/43) of the women were obese, 56% (23/41) had abnormal total cholesterol levels and 30% (13/43) had high fasting blood glucose. Vitamin D levels were considered deficient or inadequate in 37% of women. We did not see significant correlations of prolactin with laboratory measures, however all female patients had elevated and high prolactin levels, leading to low variability in a small sample, which may have precluded seeing any direct relationships. Recognizing prolactin related side effects and understanding the role of other health measures seen in women with antipsychotic induced hyperprolactinemia in our female patients are critical steps toward better personalization of their care and recovery.
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Antipsicóticos , Hiperprolactinemia , Esquizofrenia , Antipsicóticos/efeitos adversos , Feminino , Humanos , Hiperprolactinemia/tratamento farmacológico , Gravidez , Prolactina , Vitamina D/análogos & derivadosRESUMO
Weight gain is a major adverse effect of several second-generation antipsychotic medications. Rimonabant is a cannabinoid-1 receptor antagonist that promotes weight loss in the general population. We conducted a 16-week, double-blind, placebo-controlled study of rimonabant (20 mg/d) in people with schizophrenia or schizoaffective disorder, based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, who were clinically stable on second-generation antipsychotics. Participants had a body mass index of 27 kg/m or higher with hyperlipidemia or body mass index of 30 kg/m or higher, and no current substance abuse/dependence (except nicotine), more than weekly cannabis use, or recent depressive symptoms/suicidality. An exercise and dietary counseling group was offered weekly. Target enrollment was 60; the trial was terminated early because of withdrawal of rimonabant from the European market. Fifteen participants were randomized (7 rimonabant, 8 placebo); 5 completed in each group. Rimonabant was associated with a greater reduction in Brief Psychiatric Rating Scale total score versus placebo (mean ± SE difference, -1.9 ± 0.8, P = 0.02), driven by differences in the Brief Psychiatric Rating Scale anxiety/depression (-1.4 ± 0.35, P = 0.0004) and hostility (-0.7 ± 0.3, P = 0.02) factors. Group differences were not significant for the Calgary Depression Scale total score (P = 0.24), Scale for the Assessment of Negative Symptoms total score (P = 0.13), weight, blood pressure, or fasting lipids or glucose. Rimonabant was well tolerated with no significant adverse events. No significant weight loss, metabolic effects, or adverse psychiatric effects were associated with the cannabinoid-1 receptor antagonist rimonabant in this small sample of people with schizophrenia. The endocannabinoid system remains a promising target for pharmacotherapy of schizophrenia and obesity.
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Sobrepeso/tratamento farmacológico , Sobrepeso/psicologia , Piperidinas/uso terapêutico , Pirazóis/uso terapêutico , Receptor CB1 de Canabinoide/antagonistas & inibidores , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso/induzido quimicamente , Projetos Piloto , Piperidinas/farmacologia , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/fisiologia , RimonabantoRESUMO
Clozapine is a superior agent for treatment-refractory patients with schizophrenia, but is underutilized in the US, likely due to the risk of side effects. This study examined all available autopsy data on cardiac disease and risk factors in people with schizophrenia in a sample of deceased persons with severe mental illness who had received clozapine (N=62) or risperidone (N=42). The mean body mass index (BMI) at the time of death was 31.4+/-8.8 kg/m2 and 27.1+/-8.2 kg/m2 in the clozapine and risperidone groups respectively (t=1.98, df=60, p=0.052). Cardiac related measures examined included: abdominal wall thickness, heart weight, left ventricle thickness, right ventricle thickness, presence of notable cardiac involvement (atherosclerosis, fibrosis and hypertrophy) and number of cardiac arteries occluded. No significant differences in any of the cardiac findings were noted between patients in the clozapine and risperidone groups. Independent of treatment, cardiomyopathy deaths were associated with a higher abdominal wall thickness (p=0.042) and a tendency towards higher BMI (p=0.051) as compared to the other causes of death. The results of this study suggest that while clozapine is associated with weight gain and metabolic abnormalities, there does not appear to be an increased occurrence of cardiac abnormalities in deceased persons who were treated with clozapine as compared to risperidone.