RESUMO
RATIONALE: Inadequate responses to current schizophrenia treatments have accelerated research into novel therapeutic approaches. OBJECTIVES: This study investigated the efficacy and tolerability of adjunctive L-theanine, an ingredient with neuroimmunomodulatory and neuroprotective properties, for chronic schizophrenia. METHODS: Eighty chronic schizophrenia inpatients were equally assigned to receive risperidone (6 mg/day) plus either L-theanine (400 mg/day) or matched placebo in this 8-week, randomized, parallel-group, double-blind, placebo-controlled trial. The participants were assessed using the Positive and Negative Syndrome Scale (PANSS) by recording the results of subscales at baseline and weeks 4 and 8 to measure treatment efficacy. Additionally, the participants were assessed for the Hamilton Depression Rating Scale (HDRS) and adverse events, including the Extrapyramidal Symptom Rating Scale (ESRS). RESULTS: Sixty patients, 30 in each group, were included in the analyses. All baseline demographic and clinical characteristics were comparable between the groups (p-values > 0.05). The reduction rates from baseline to endpoint in negative, general psychopathology, and total scores of PANSS were greater in the L-theanine group (p-values = 0.03, 0.01, and 0.04, respectively). Regarding general psychopathology scores, the reduction in the L-theanine group was also greater until week 4 (p-value < 0.01). The time × treatment interaction effect was significant on negative (p-value = 0.03), general psychopathology (p-value < 0.01), and total (p-value = 0.04) scores of PANSS, indicating additional improvements in the L-theanine group. The HDRS and side effects were comparable between the groups (p-values > 0.05). CONCLUSIONS: L-Theanine adjunct to risperidone safely and tolerably outperformed adjunctive placebo for schizophrenia, and promising evidence indicated its effects on primary negative symptoms, which need to be scrutinized in further studies. TRIAL REGISTRATION: The study protocol was registered and published prospectively in the Iranian Registry of Clinical Trials ( http://www.irct.ir ; registration number: IRCT20090117001556N133) on 2020-12-12.
Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Risperidona/uso terapêutico , Risperidona/efeitos adversos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/induzido quimicamente , Antipsicóticos/efeitos adversos , Pacientes Internados , Irã (Geográfico) , Quimioterapia Combinada , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Método Duplo-CegoRESUMO
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects 0.6%-1.7% of children. The etiology of autism is hypothesized to include both biological and environmental factors (Watts, 2008). In addition to the core symptoms of social-communication delay and restricted, repetitive interests, co-occurring irritability/aggression, hyperactivity, and insomnia negatively impact adaptive functioning and quality of life of patients and families. Despite years of effort, no pharmacologic agent has been found that targets the core symptoms of ASD. The only FDA-approved agents are risperidone and aripiprazole for agitation and irritability in ASD, not for core symptoms. Though they effectively reduce irritability/violence, they do so at the expense of problematic side effects: metabolic syndrome, elevated liver enzymes, and extrapyramidal side effects. Thus, it is not surprising that many families of children with ASD turn to nonallopathic treatment, including dietary interventions, vitamins, and immunomodulatory agents subsumed under complementary-integrative medicine (CIM). Per recent studies, 27% to 88% of families report using a CIM treatment. In an extensive population-based survey of CIM, families of children with more severe ASD, comorbid irritability, GI symptoms, food allergies, seizures, and higher parental education tend to use CIM at higher rates. The perceived safety of CIM treatments as "natural treatment" over allopathic medication increases parental comfort in using these agents. The most frequently used CIM treatments include multivitamins, an elimination diet, and Methyl B12 injections. Those perceived most effective are sensory integration, melatonin, and antifungals. Practitioners working with these families should improve their knowledge about CIM as parents currently perceive little interest in and poor knowledge of CIM by physicians. This article reviews the most popular complementary treatments preferred by families with children with autism. With many of them having limited or poor quality data, clinical recommendations about the efficacy and safety of each treatment are discussed using the SECS versus RUDE criteria.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Medicina Integrativa , Criança , Humanos , Transtorno do Espectro Autista/tratamento farmacológico , Qualidade de Vida , Risperidona/uso terapêuticoAssuntos
Agressão , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/tratamento farmacológico , Antipsicóticos/uso terapêutico , Sistema Único de Saúde , Brasil , Terapia Cognitivo-Comportamental/instrumentação , Análise Custo-Benefício , Risperidona/uso terapêutico , Análise do Comportamento Aplicada/instrumentação , Musicoterapia/instrumentaçãoRESUMO
In 2011, the European Society for the Study of Tourette Syndrome (ESSTS) published the first European guidelines for Tourette Syndrome (TS). We now present an update of the part on pharmacological treatment, based on a review of new literature with special attention to other evidence-based guidelines, meta-analyses, and randomized double-blinded studies. Moreover, our revision took into consideration results of a recent survey on treatment preferences conducted among ESSTS experts. The first preference should be given to psychoeducation and to behavioral approaches, as it strengthens the patients' self-regulatory control and thus his/her autonomy. Because behavioral approaches are not effective, available, or feasible in all patients, in a substantial number of patients pharmacological treatment is indicated, alone or in combination with behavioral therapy. The largest amount of evidence supports the use of dopamine blocking agents, preferably aripiprazole because of a more favorable profile of adverse events than first- and second-generation antipsychotics. Other agents that can be considered include tiapride, risperidone, and especially in case of co-existing attention deficit hyperactivity disorder (ADHD), clonidine and guanfacine. This view is supported by the results of our survey on medication preference among members of ESSTS, in which aripiprazole was indicated as the drug of first choice both in children and adults. In treatment resistant cases, treatment with agents with either a limited evidence base or risk of extrapyramidal adverse effects might be considered, including pimozide, haloperidol, topiramate, cannabis-based agents, and botulinum toxin injections. Overall, treatment of TS should be individualized, and decisions based on the patient's needs and preferences, presence of co-existing conditions, latest scientific findings as well as on the physician's preferences, experience, and local regulatory requirements.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtornos de Tique , Síndrome de Tourette , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Criança , Feminino , Guanfacina/uso terapêutico , Humanos , Masculino , Risperidona/uso terapêutico , Transtornos de Tique/complicações , Transtornos de Tique/tratamento farmacológico , Síndrome de Tourette/complicações , Síndrome de Tourette/tratamento farmacológicoRESUMO
BACKGROUND: Cannabis use is an important risk factor for development of psychosis and further transition to schizophrenia. The prevalence of patients with psychosis and comorbid cannabis use (dual diagnosis) is rising with no approved specialized pharmacological treatment option. Cannabidiol, a constituent of the Cannabis sativa plant, has potential both as an antipsychotic and as a cannabis substituting agent. The aim of this study is to evaluate the efficacy of cannabidiol versus a first-choice second-generation antipsychotic (risperidone) in patients with early psychosis and comorbid cannabis use. METHODS: The study is a phase II randomized, double-blinded, parallel-group, active-comparator clinical trial. We plan to include 130 patients aged between 18 and 64 years with a recent diagnosis of psychosis, comorbid cannabis use, and currently not treated with antipsychotics. The participants will be randomized to seven weeks of treatment with either cannabidiol 600 mg (300 mg BID) or risperidone 4 mg (2 mg BID). Participants will undergo clinical assessment after 1, 3, 5 and 7 weeks, telephone assessment the weeks in between, and a safety visit two weeks after end of treatment. The primary outcomes are cessation of cannabis use (self-reported) and psychotic symptom severity. The secondary outcomes include frequency and quantity of cannabis use, global illness severity, psychosocial functioning, subjective well-being, cognition, sleep, circadian rhythmicity, and metabolomics. DISCUSSION: The results of this trial can potentially contribute with a new treatment paradigm for patients suffering from dual diagnosis. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04105231 , registered April 23rd, 2021.
Assuntos
Antipsicóticos , Canabidiol , Cannabis , Transtornos Psicóticos , Adolescente , Adulto , Antipsicóticos/uso terapêutico , Canabidiol/uso terapêutico , Humanos , Pessoa de Meia-Idade , Transtornos Psicóticos/complicações , Transtornos Psicóticos/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Risperidona/uso terapêutico , Adulto JovemRESUMO
Multiple sclerosis (MS) is a demyelinating, autoimmune disease that affects a large number of young adults. Novel therapies for MS are needed considering the efficiency and safety limitations of current treatments. In our study, we investigated the effects of venlafaxine (antidepressant, serotonin-norepinephrine reuptake inhibitor), risperidone (atypical antipsychotic) and febuxostat (gout medication, xanthine oxidase inhibitor) in the cuprizone mouse model of acute demyelination, hypothesizing an antagonistic effect on TRPA1 calcium channels. Cuprizone and drugs were administered to C57BL6/J mice for five weeks and locomotor activity, motor performance and cold sensitivity were assessed. Mice brains were harvested for histological staining and assessment of oxidative stress markers. Febuxostat and metabolites of venlafaxine (desvenlafaxine) and risperidone (paliperidone) were tested for TRPA1 antagonistic activity. Following treatment, venlafaxine and risperidone significantly improved motor performance and sensitivity to a cold stimulus. All administered drugs ameliorated the cuprizone-induced deficit of superoxide dismutase activity. Desvenlafaxine and paliperidone showed no activity on TRPA1, while febuxostat exhibited agonistic activity at high concentrations. Our findings indicated that all three drugs offered some protection against the effects of cuprizone-induced demyelination. The agonistic activity of febuxostat can be of potential use for discovering novel TRPA1 ligands.
Assuntos
Febuxostat/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Neurotransmissores/uso terapêutico , Risperidona/uso terapêutico , Cloridrato de Venlafaxina/uso terapêutico , Animais , Corpo Caloso/efeitos dos fármacos , Cuprizona , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Febuxostat/farmacologia , Feminino , Células HEK293 , Humanos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Neurotransmissores/farmacologia , Risperidona/farmacologia , Canal de Cátion TRPA1/efeitos dos fármacos , Cloridrato de Venlafaxina/farmacologiaRESUMO
Alterations in polyunsaturated fatty acids (PUFAs), including omega-3 and omega-6, have been implicated in the pathophysiology of psychotic disorders, but little is known about their associations with neuropsychological functioning. The present study includes 46 recent-onset psychosis patients who participated in a larger (n = 50) double blind, placebo-controlled randomized clinical trial comparing 16 weeks of treatment with either risperidone + fish oil (FO) (EPA 740 mg and DHA 400 mg daily) or risperidone + placebo and completed neuropsychological assessments at the baseline timepoint. We investigated the relationship between baseline omega-3 (i.e., eicosapentaenoic acid, EPA; docosapentaenoic acid, DPA and docosahexaenoic acid, DHA) and omega-6 (i.e., arachidonic acid, AA) PUFA with baseline MATRICS Consensus Cognitive Battery (MCCB) and Brief Psychiatric Rating Scale (BPRS) scores. Twenty-five patients had neuropsychological data available at 16 weeks following participation in the clinical trial, which included 12 patients assigned to risperidone + FO and 13 patients assigned to risperidone + placebo. At baseline both higher DHA and EPA correlated significantly with better social cognition after controlling for functioning on other neuropsychological domains, total BPRS score, AA level and substance use. Also, at baseline higher AA correlated significantly with hostility/uncooperativeness after controlling for DHA + EPA + DPA, overall neuropsychological functioning and substance use. Patients treated with risperidone + FO demonstrated a significant longitudinal increase in social cognition that was significantly higher at 16 weeks compared to patients treated with risperidone + placebo. DHA also correlated significantly with social cognition at the 16-week timepoint. This study provides novel evidence for a differential role of omega-3 vs. omega-6 PUFA in neuropsychological deficits and symptoms in recent-onset psychosis and its treatment.
Assuntos
Ácidos Graxos Ômega-3 , Transtornos Psicóticos , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico , Ácidos Graxos Insaturados , Humanos , Transtornos Psicóticos/complicações , Transtornos Psicóticos/tratamento farmacológico , Risperidona/uso terapêuticoRESUMO
We examined the impact of treatment with fish oil (FO), a rich source of omega-3 polyunsaturated fatty acids (n-3 PUFA), on white matter in 37 recent-onset psychosis patients receiving risperidone in a double-blind placebo-controlled randomized clinical trial. Patients were scanned at baseline and randomly assigned to receive 16-weeks of treatment with risperidone + FO or risperidone + placebo. Eighteen patients received follow-up MRIs (FO, n = 10/Placebo, n = 8). Erythrocyte levels of n-3 PUFAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA) were obtained at both time points. We employed Free Water Imaging metrics representing the extracellular free water fraction (FW) and fractional anisotropy of the tissue (FA-t). Analyses were conducted using Tract-Based-Spatial-Statistics and nonparametric permutation-based tests with family-wise error correction. There were significant positive correlations of FA-t with DHA and DPA among all patients at baseline. Patients treated with risperidone + placebo demonstrated reductions in FA-t and increases in FW, whereas patients treated with risperidone + FO exhibited no significant changes in FW and FA-t reductions were largely attenuated. The correlations of DPA and DHA with baseline FA-t support the hypothesis that n-3 PUFA intake or biosynthesis are associated with white matter abnormalities in psychosis. Adjuvant FO treatment may partially mitigate against white matter alterations observed in recent-onset psychosis patients following risperidone treatment.
Assuntos
Ácidos Graxos Ômega-3 , Transtornos Psicóticos , Substância Branca , Ácidos Graxos Insaturados , Humanos , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/tratamento farmacológico , Risperidona/farmacologia , Risperidona/uso terapêutico , Substância Branca/diagnóstico por imagemRESUMO
Introduction: Antipsychotics are widely prescribed for patients with schizophrenia. The Brazilian public health system provides these patients free of charge to patients and it is pertinent to evaluate their benefits.Objective: To evaluate the effectiveness of olanzapine and risperidone in the treatment of patients with schizophrenia in the real-world and assessing risk factors for their discontinuation through a national non-concurrent cohort with 16 years of follow-up.Methods: Three SUS administrative databases were integrated by deterministic-probabilistic linkage. After patients were matched (1:1) for psychiatric hospitalization, year of receiving the antipsychotic, sex, and age, considering either olanzapine or risperidone at study entry. Kaplan-Meier was used to estimate the cumulative probabilities of discontinuation of treatment and associated factors were identified. Sensitivity analyses were performed.Results: 3416 pairs of patients were included. Olanzapine had a longer time until discontinuation of treatment (p = 0.021), and risperidone had a higher risk of discontinuation (p = 0.021). Among patients persistent for at least 24 months, there was no statistically significant difference.Conclusion: Olanzapine demonstrated superior real-world effectiveness over risperidone, in terms of survival and psychiatric hospitalization. This superiority was not sustained in all analyses.
Assuntos
Antipsicóticos/uso terapêutico , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Brasil , Estudos de Coortes , Bases de Dados Factuais , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemAssuntos
Acetilcarnitina/efeitos adversos , COVID-19 , Delusões/induzido quimicamente , Suplementos Nutricionais/efeitos adversos , Transtornos Paranoides/induzido quimicamente , Psicoses Induzidas por Substâncias/etiologia , Complexo Vitamínico B/efeitos adversos , Antipsicóticos/uso terapêutico , Delusões/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Paranoides/tratamento farmacológico , Psicoses Induzidas por Substâncias/tratamento farmacológico , Risperidona/uso terapêuticoRESUMO
INTRODUCTION: With the second-generation antipsychotics (SGAs) widely applied to treat patients with schizophrenia, adverse effects, especially the metabolic syndrome (MetS), were paid more attention following by the efficacy of SGAs. Several studies have suggested that acupuncture could be an effective and safe intervention for MetS. Here, we present a study protocol to investigate the effect of electroacupuncture on MetS due to olanzapine and risperidone. METHODS: This study is a prospective, randomized, single-centered, patient-assessor-blinded, parallel-controlled clinical pilot trial. In all, 36 patients will be randomized to an experimental group or control group by a 1:1 ratio. All patients will receive lifestyle interventions. The experimental group will receive electroacupuncture treatment. The control group will receive sham electroacupuncture treatment. The primary outcomes are body mass index (BMI) and waist circumference (WC). The secondary outcome measures include blood pressure (BP), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), leptin, and adiponectin. We will assess at baseline, 8 weeks after intervention and at the end of 3 months' follow-up. DISCUSSION: The results of this trial are expected to provide data on the efficacy and safety of electroacupuncture on MetS due to olanzapine and risperidone, and potential biochemical mechanism.
Assuntos
Antipsicóticos/efeitos adversos , Eletroacupuntura , Síndrome Metabólica/terapia , Olanzapina/efeitos adversos , Risperidona/efeitos adversos , Antipsicóticos/uso terapêutico , Protocolos Clínicos , Eletroacupuntura/efeitos adversos , Eletroacupuntura/métodos , Humanos , Síndrome Metabólica/induzido quimicamente , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológicoRESUMO
BACKGROUND: Introduction of old and new generations of antipsychotics leads to significant improvements in the positive symptoms of schizophrenia. However, negative symptoms remain refractory to conventional trials of antipsychotic therapy. Recently, there were several open clinical human trials with curcumin. Curcumin is a natural polyphenol, which has a variety of pharmacological activities, including antioxidative and neuroprotective effects. The studies showed that curcumin improved the negative symptoms of schizophrenia. The purpose of our study was to examine the efficacy of curcumin as an add-on agent to regular antipsychotic medications in patients with chronic schizophrenia. METHODS: Thirty-eight patients with chronic schizophrenia were enrolled in a 24-week, double-blind, randomized, placebo-controlled study. The subjects were treated with either 3000 mg/d curcumin or placebo combined with antipsychotics from January 2015 to February 2017. The outcome measures were the Positive and Negative Symptoms Scale (PANSS) and the Calgary Depression Scale for Schizophrenia. RESULTS: Analysis of variance showed significant positive changes in both groups from baseline to the end of the study in all scales of measurement. There was a significant response to curcumin within 6 months in total PANSS (P = 0.02) and in the negative symptoms subscale (P = 0.04). There were no differences in the positive and general PANSS subscales, and the Calgary Depression Scale for Schizophrenia scores between the treatment and placebo groups. No patient complained of any adverse effect. CONCLUSIONS: The promising results of curcumin as an add-on to antipsychotics in the treatment of negative symptoms may open a new and safe therapeutic option for the management of schizophrenia. However, these results should be replicated in further studies.ClinicalTrials.gov Identifier: NCT02298985.
Assuntos
Antipsicóticos/uso terapêutico , Curcumina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Risperidona/uso terapêuticoAssuntos
Meditação/psicologia , Transtornos Psicóticos/etiologia , Adulto , Antipsicóticos/uso terapêutico , Moduladores GABAérgicos/uso terapêutico , Haloperidol/uso terapêutico , Humanos , Lorazepam/uso terapêutico , Masculino , Prometazina/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Risperidona/uso terapêuticoRESUMO
OBJECTIVES: Although second generation long-acting injectable antipsychotics (SG-LAIAs) have been approved and are widely used in adults, there is limited evidence for the use of long-acting formulations in children and adolescents. Thus, we systematically describe the off-label use of SG-LAIAs in clinical practice in adolescent inpatients. METHODS: All individuals admitted to our Children and Adolescent Inpatient Psychiatry Unit receiving treatment with SG-LAIAs between January 2013 and June 2016 were reviewed. A retrospective analysis of medical records was conducted. Clinical diagnoses were established using DSM-5 criteria. RESULTS: Thirty individuals (53.3% female) out of a total of 1,148 admitted patients (2.6%) were identified. The mean age was 16.3 (SD = 1.3; range: 12.5-17.9).The main diagnoses were psychosis (70%) and disruptive behavior disorders (DBDs) (30%), although comorbidity was frequent (96.6%), especially drug use (55.2%, mostly cannabis). SG-LAIAs used were aripiprazole (40%), risperidone (36.7%), and paliperidone palmitate (23.3%), and the main reasons were a history of low compliance (90%) and/or poor insight (73.3%). A mean improvement of 31.7 (SD = 8.7) between admission and discharge was registered in the Children's Global Assessment Scale (CGAS); no differences were observed between different SG-LAIAs. Although they were generally well tolerated, 23.3% of patients reported mild short-term side effects, which were more frequent with risperidone than with aripiprazole (p = .014). CONCLUSIONS: Our clinical experience suggests that SG-LAIAs may be a safe treatment option during adolescence in inpatients with psychotic disorders, as well as with DBD. No differences were found in CGAS improvement scores between the three SGA-LAIAs used, although patients on risperidone reported more side effects than those on aripiprazole. Further research is needed so as to evaluate safety and effectiveness of SG-LAIAs in this population.
Assuntos
Antipsicóticos/uso terapêutico , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Adolescente , Antipsicóticos/efeitos adversos , Aripiprazol/efeitos adversos , Aripiprazol/uso terapêutico , Criança , Preparações de Ação Retardada , Feminino , Hospitalização , Humanos , Pacientes Internados , Masculino , Uso Off-Label , Palmitato de Paliperidona/efeitos adversos , Palmitato de Paliperidona/uso terapêutico , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/fisiopatologia , Estudos Retrospectivos , Risperidona/efeitos adversos , Risperidona/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Up to 75% of people with serious mental illness (SMI) such as schizophrenia and bipolar disorder have co-occurring substance use disorders (dual diagnosis). Dual diagnosis can have an adverse effect on treatment and prognosis of SMI. OBJECTIVES: To evaluate the effects of risperidone compared to treatment with other antipsychotics (first-generation and other second-generation antipsychotics) used in people with serious mental illness and co-occurring substance misuse. SEARCH METHODS: On 6 January 2016 and 9 October 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (including trial registers). SELECTION CRITERIA: We selected randomised trials of risperidone versus any other antipsychotic in people with SMI and substance abuse (dual diagnosis). We included trials meeting our inclusion criteria and reporting useable data. We excluded trials that either did not meet our inclusion criteria or met our inclusion criteria but did not report any useable data. DATA COLLECTION AND ANALYSIS: We independently inspected citations and selected studies. For included studies, we independently extracted data and appraised study quality. For binary outcomes we calculated the risk ratios (RRs) and their 95% confidence intervals. For continuous outcomes we calculated the mean differences (MDs) and their 95% confidence intervals. We pooled data using random-effects meta-analyses and assessed the quality of evidence, creating a 'Summary of findings' table using the GRADE approach. MAIN RESULTS: We identified eight randomised trials containing a total of 1073 participants with SMI and co-occurring substance misuse. Seven of these contributed useable data to the review. There was heterogeneity in trial design and measurement. Risperidone was compared to clozapine, olanzapine, perphenazine, quetiapine and ziprasidone. Few trials compared risperidone with first-generation agents. Few trials examined participants with a dual diagnosis from the outset and most trials only contained separate analyses of subgroups with a dual diagnosis or were secondary data analyses of subgroups of people with a dual diagnosis from existing larger trials.For risperidone versus clozapine we found no clear differences between these two antipsychotics in the reduction of positive psychotic symptoms (1 randomised controlled trial (RCT), n = 36, mean difference (MD) 0.90, 95% CI -2.21 to 4.01, very low quality evidence), or reduction in cannabis use (1 RCT, n = 14, risk ratio (RR) 1.00, 95% CI 0.30 to 3.35, very low quality evidence), improvement in subjective well-being (1 RCT, n = 36, MD -6.00, 95% CI -14.82 to 2.82, very low quality evidence), numbers discontinuing medication (1 RCT, n = 36, RR 4.05, 95% CI 0.21 to 78.76, very low quality evidence), extrapyramidal side-effects (2 RCTs, n = 50, RR 2.71, 95% CI 0.30 to 24.08; I² = 0%, very low quality evidence), or leaving the study early (2 RCTs, n = 45, RR 0.49, 95% CI 0.10 to 2.51; I² = 34%, very low quality evidence). Clozapine was associated with lower levels of craving for cannabis (1 RCT, n = 28, MD 7.00, 95% CI 2.37 to 11.63, very low quality evidence).For risperidone versus olanzapine we found no clear differences in the reduction of positive psychotic symptoms (1 RCT, n = 37, MD -1.50, 95% CI -3.82 to 0.82, very low quality evidence), reduction in cannabis use (1 RCT, n = 41, MD 0.40, 95% CI -4.72 to 5.52, very low quality evidence), craving for cannabis (1 RCT, n = 41, MD 5.00, 95% CI -4.86 to 14.86, very low quality evidence), parkinsonism (1 RCT, n = 16, MD -0.08, 95% CI -1.21 to 1.05, very low quality evidence), or leaving the study early (2 RCT, n = 77, RR 0.68, 95% CI 0.34 to 1.35; I² = 0%, very low quality evidence).For risperidone versus perphenazine, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 281, RR 1.05, 95% CI 0.92 to 1.20, low-quality evidence).For risperidone versus quetiapine, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 294, RR 0.96, 95% CI 0.86 to 1.07, low-quality evidence).For risperidone versus ziprasidone, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 240, RR 0.96, 95% CI 0.85 to 1.10, low-quality evidence).For many comparisons, important outcomes were missing; and no data were reported in any study for metabolic disturbances, global impression of illness severity, quality of life or mortality. AUTHORS' CONCLUSIONS: There is not sufficient good-quality evidence available to determine the effects of risperidone compared with other antipsychotics in people with a dual diagnosis. Few trials compared risperidone with first-generation agents, leading to limited applicability to settings where access to second-generation agents is limited, such as in low- and middle-income countries. Moreover, heterogeneity in trial design and measurement of outcomes precluded the use of many trials in our analyses. Future trials in this area need to be sufficiently powered but also need to conform to consistent methods in study population selection, use of measurement scales, definition of outcomes, and measures to counter risk of bias. Investigators should adhere to CONSORT guidelines in the reporting of results.
Assuntos
Antipsicóticos/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Risperidona/uso terapêutico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Benzodiazepinas/uso terapêutico , Clozapina/uso terapêutico , Diagnóstico Duplo (Psiquiatria) , Humanos , Olanzapina , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Perfenazina/uso terapêutico , Piperazinas/uso terapêutico , Fumarato de Quetiapina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/psicologia , Tiazóis/uso terapêuticoRESUMO
OBJECTIVE: Cannabis use disorders (CUDs) are highly comorbid in patients with schizophrenia and associated with poor outcome. Clozapine has been put forward as the first choice antipsychotic in this patient group. However, little is known about the mechanisms underlying the assumed superiority of clozapine. METHODS: A total of 38 patients with DSM-IV schizophrenia (30 with and 8 without a DSM-IV CUD) and 20 healthy comparison subjects were included between April 2009 and June 2012. Patients were randomized to antipsychotic treatment with clozapine or risperidone. At baseline and after 4weeks of medication, brain response to cannabis-related, positive and neutral images was measured using functional MRI. Neural correlates of cue reactivity were assessed in the following regions of interest: amygdala, ventral striatum, insula, thalamus, orbitofrontal cortex and anterior cingulate cortex. Subjective craving was assessed using self-report questionnaires (OCDUS and MCQ). RESULTS: At baseline, patients with a comorbid CUD showed higher subjective craving and greater activation in response to cannabis-related images compared to patients without a CUD and healthy controls in most regions of interest. Clozapine treated patients reported a greater reduction in craving (F(1,28)=6.0, p=0.04) and showed a larger decrease in amygdala activation during cannabis-related images compared to risperidone treated patients (T=3.94, pFWE=0.006). In addition, significant correlations were found between subjective craving and thalamus and insula activation during cannabis-related images. CONCLUSION: These findings provide evidence that clozapine is superior to risperidone in decreasing subjective craving and cue reactivity for cannabis-related images probably due to a differential effect on dopaminergic neurotransmission. TRIAL REGISTRATION: 'Nederlands trial register' (http://www.trialregister.nl), nr NTR1761, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1761.
Assuntos
Antipsicóticos/uso terapêutico , Encéfalo/efeitos dos fármacos , Clozapina/uso terapêutico , Abuso de Maconha/complicações , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Comorbidade , Fissura/efeitos dos fármacos , Fissura/fisiologia , Sinais (Psicologia) , Humanos , Imageamento por Ressonância Magnética , Masculino , Abuso de Maconha/diagnóstico por imagem , Abuso de Maconha/fisiopatologia , Adesão à Medicação , Esquizofrenia/complicações , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia , Resultado do Tratamento , Percepção Visual/efeitos dos fármacos , Percepção Visual/fisiologia , Adulto JovemRESUMO
BACKGROUND: In recent years, there has been a reported increase in affliction of the skin with small fibres or other particles. The condition has been referred to as Morgellons disease. Patients present with stinging, burning or crawling sensations of the skin, with perceived extrusion of inanimate material alongside fatigue and other systemic symptoms. Sufferers often experience significant morbidity and reduction in quality of life. OBJECTIVES: We aimed to explore the various clinical presentations, management strategies and outcomes employed to treat this condition in our patients. METHODS: We conducted a retrospective case notes review of 35 patients referred to our multidisciplinary psycho-dermatology clinic at the Royal London Hospital between January 2004 and January 2017. RESULTS: The majority of patients were women (25) 71.4%, with a mean age of 54.6 years (26-80 years). Most (26) 74.2% were living alone. The average duration of illness prior to presentation was 3.8 years (4 months-20 years). Many patients had perceived precipitating factors (54.2%) and often self-diagnosed (28.5%). Psychiatric co-morbidities included 42.8% with depressive symptoms and 25.7% with anxiety. Substance misuse was elicited in five patients (14%). Management of patients included both the treatment of skin disease and psychosocial co-morbidities. Out of the 35 patients who attended (14) 40% cleared or showed significant improvement. Sixteen (45.7%) patients were stable and under review. One patient declined treatment and three did not attend review. One patient died from disease unrelated to her skin condition. CONCLUSIONS: Morgellons disease is a condition, which is widely discussed on the internet and patients often self-diagnose. The course of the disease can be chronic and debilitating. For a positive outcome, it is important that a strong physican-patient relationship is cultivated. As demonstrated in this case series, managing patients holistically in an integrated multidisciplinary dermatology setting helps achieve positive outcomes.
Assuntos
Anti-Infecciosos Locais/uso terapêutico , Doença de Morgellons/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos/uso terapêutico , Ansiedade/complicações , Ansiedade/patologia , Citalopram/uso terapêutico , Transtorno Depressivo/complicações , Transtorno Depressivo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Morgellons/complicações , Doença de Morgellons/patologia , Estudos Retrospectivos , Risperidona/uso terapêutico , Resultado do TratamentoRESUMO
The purpose of this nationwide population-based study is to compare the long-term effectiveness of brand-name antipsychotics with generic antipsychotics for treating schizophrenia. We identified patients with schizophrenia who were prescribed antipsychotics from a random sample of one million records from Taiwan's National Health Insurance database, observed between January 1, 2000 and December 31, 2012. Only those with no prior use of antipsychotics for at least 180days were included. We selected patients who were prescribed brand-name risperidone (N=404), generic risperidone (N=145), brand-name sulpiride (N=334), or generic sulpiride (N=991). The effectiveness of the treatments researched in this study consisted of average daily doses, rates of treatment discontinuation, augmentation therapy, and psychiatric hospitalization. We found that compared to patients treated with generic risperidone, those treated with brand-name risperidone required lower daily doses (2.14mg vs. 2.61mg). However, the two groups demonstrated similar rates of treatment discontinuation, augmentation, and psychiatric hospitalization. On the other hand, in comparison with patients prescribed generic sulpiride, those treated with brand-name sulpiride not only required lower daily doses (302.72mg vs. 340.71mg) but also had lower psychiatric admission rates (adjusted hazard ratio: 0.24, 95% confidence interval: 0.10-0.56). In conclusion, for both risperidone and sulpiride, higher daily doses of the respective generic drugs were prescribed than with brand-name drugs in clinical settings. Furthermore, the brand-name sulpiride is more effective at preventing patients from hospitalization than generic sulpiride. These findings can serve as an important reference for clinical practices and healthcare economics for treating schizophrenic patients.