Class of 2008 Abstract / Objectives: To assess the effect of treatment with placebo on weight loss in obese patients. Methods: The placebo groups from nine orlistat and three sibutramine weight loss studies, as identified from the Padwal meta-analysis, were analyzed for: weight loss in kilograms; change in BMI; type of nutrition and exercise interventions; and bias. The means and standard deviations for weight loss were entered into the Stata meta-analysis program to obtain a forest plot to determine an overall estimate of weight loss. The Potential for Methodological Bias Assessment Tool (PMBAT) was used to create a bias score for each study. Results: Overall, subjects in the placebo group lost 3.8 kg (p<0.001). Placebo subjects in the orlistat trials lost significantly more weight (4.3 kg) than did subjects in the sibutramine trials (1.1 kg, p=0.014). The subjects in the sibutramine studies did not lose a significant amount of weight (p=0.397). There were distinct differences between the sibutramine and orlistat studies with regard to nutrition and exercise interventions. The mean score on the PMBAT was 16.7 ± 3.6; and no study scored higher than 25 out of 45 total points. Conclusions: Overall subjects in the placebo group in the combined orlistat and sibutramine studies lost a significant amount of weight. Differences in study design, bias, and the Hawthorne effect may have contributed to this weight loss.

Conclusions. The retractable non-invasive needle seems to have reasonably good capability of blinding patients and is more successful in acupuncture-naive subjects than in experienced ones. The failure to produce similar sensation of stimulation in the sham acupuncture group may be the major reason for incomplete blinding. (Abstract shortened by UMI.) / Design, participants and outcomes. We conducted a randomized controlled trial of 398 acupuncture-naive subjects and 197 acupuncture-experienced subjects who were recruited from the outpatients clinic of a university hospital in China. Acupuncture-naive and experienced subjects were randomized separately to receive the real acupuncture treatment or the placebo acupuncture at acupoint Hegu on the left hand. After the intervention, the percentage of patients who thought they had received real acupuncture was compared between the real and sham acupuncture groups. We defined the degree of blinding as 100% minus the difference in the percentage between the two groups. The score of pain, soreness, numbness, heaviness and distension during the treatment was also compared between the two groups. / Introduction. The newly designed retractable needle which can be used to produce non-invasive placebo or (sham) acupuncture seems promising and has been used in clinical trials. Several studies investigated the credibility of the retractable needle in blinding patients. These studies are generally small and mostly in acupuncture-naive patients and mainly focused on the difference in acupuncture-related sensations rather than the successfulness of blinding. / Objectives. To quantify the degree of blinding of the retractable non-invasive placebo needle in blinding both acupuncture-naive and experienced subjects in clinical trials and to explore possible reasons for incomplete blinding of the sham needle. / Results. In acupuncture-naive subjects, the percentage of those who thought they had received real acupuncture was 70.4% and 42.7% respectively in the real and sham acupuncture groups. The degree of blinding was 72.3% (95% CI: 62.9%, 81.7%). In acupuncture-experienced subjects, the degree of blinding was 58.9 (95% CI: 46.2%, 71.6%). The difference in degree of blinding between acupuncture-naive and experienced subjects was statistically significant (P&lt;0.05). The score of pain, soreness, numbness, heaviness and distension in the real acupuncture group was all statistically significantly higher than that in the sham acupuncture group in both acupuncture-naive and experienced subjects (P&lt;0.001). / Zhang Hongwei. / "February 2005." / Adviser: Jin Ling Tang. / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0161. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 93-102). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

A desregulação glutamatérgica parece ter uma importante participação na neurofisiopatologia da esquizofrenia, principalmente através da disfunção do receptor NMDA. A Memantina, uma droga aprovada pelo FDA para o tratamento da doença de Alzheimer de grau moderado a severo age como um antagonista fraco e não seletivo dos receptores NMDA. O objetivo deste estudo é examinar a eficácia da memantina como tratamento adjuvante à clozapina em pacientes com esquizofrenia refratária. Métodos: Em ensaio randomizado duplo cego controlado com placebo, pacientes com esquizofrenia refratária segundo os critérios do DSM-IV foram alocados aleatoriamente de março de 2005 à fevereiro de 2008 para receber 20mg/dia de memantina (n=10) ou placebo (n=11) juntamente com o tratamento padrão de clozapina. O desfecho principal analisado foi o escore total da Brief Psychiatry Rating Scale (BPRS), e suas subdivisões de sintomas positivos e sintomas negativos. Medidas secundárias observadas foram feitas através das escalas: Clinical Global Impression (CGI), cognition assessed by the Mini-Mental State Exam (MMSE), e Extrapyramidal Symptoms by the Simpson-Angus Scale (SAS). Resultados: Vinte e um participantes concluíram o estudo, e foram incluídos na análise estatística. Foi observado melhora significativa (p<0.01) na pontuação total da BPRS e suas subescalas de sintomas positivos [ES -1.38], sintomas negativos [ES -3.33], além da CGI [ES 1.56] e MMSE. Não foram observadas alterações na escala de sintomas extrapiramidais. Conclusões: A memantina como terapia adjuvante ao tratamento com clozapina em pacientes com esquizofrenia refratária está associada com melhora nos sintomas positivos e negativos Estudos que repliquem estes dados em amostras maiores e com diferentes populações são necessários para confirmar e ampliar nossos resultados. (Trial Register, clinicaltrials.gov, NCT00757978). / Background: Glutamate deregulation may be involved in the neuropathology of schizophrenia, mainly through N-methyl-d-aspartate receptor (NMDA) dysfunction. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease acts as weak non-selective NMDA receptor antagonist. The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to clozapine in patients with refractory schizophrenia. Methods: In this double-blind, placebo-controlled study, outpatients with refractory schizophrenia according DSM-IV clinical criteria were randomized from March, 2005 to February, 2008, to receive either 20 mg/day memantine (n=10) or placebo (n=11), in addition to clozapine, for 12 weeks. The primary outcome measure was the total score on the Brief Psychiatry Rating Scale (BPRS), and its subscales of positive and negative symptoms. Secondary outcomes were global severity of disease as measured by the Clinical Global Impression (CGI), cognition assessed by the Mini-Mental State Exam (MMSE), and extrapyramidal symptoms by the Simpson-Angus Scale (SAS). Results: Twenty-one participants completed the study, and were used in the analysis. Significant improvement (p<0.01) on the total BPRS score, its subscales of positive [effect size (ES) -1.38] and negative symptoms (ES –3.33), the CGI (ES size 1.56) and MMSE were observed with memantine as compared with placebo. No significant changes in extrapyramidal symptoms were observed. Conclusions: Memantine add-on to clozapine therapy was associated with improvement in negative and positive symptoms in refractory schizophrenia patients (Trial Register, clinicaltrials.gov, NCT00757978).

Pilot Study: a) 21 Generalised Anxiety Disorder (GAD) patients were treated double-blind with either diazepam or placebo for 6 weeks. This active treatment period was preceded by one-week single-blind placebo 'wash-in', and followed by two-week single-blind 'washout'. Results showed that diazepam used in moderate doses for 6 weeks produced anxiety recurrence and withdrawal symptoms. b) 10 GAD patients were randomly allocated to Cognitive-Behaviour Therapy (CBT) and compared with the above diazepam and placebo groups. All treatments were balanced for degree of Psychologist/patient contact. At cessation of active treatment CBT superiority was indicated. Post-Study psychotropic prescription and psychological treatment were assessed at 12 months follow-up. The CBT group had the lowest incidence of subsequent treatment interventions. Main Study : 101 GAD patients were randomly allocated to diazepam, placebo, CBT, CBT + diazepam, and CBT + placebo, and treated over 10 weeks. Outcome measures at end of treatment and at 6 months follow-up revealed the superiority of all CBT treatments; especially CBT alone, and CBT + diazepam. Diazepam was more effective than placebo. CBT + diazepam, and diazepam groups showed no anxiety recurrence during graded withdrawal. Secondary Study : 205 long-term benzodiazepine users were matched for age and sex with controls. Inspection of medical case notes showed that benzodiazepine users had higher rates of previous physical illness, GP attendance, and non-psychotropic drug prescription. Differences emerged between anxiolytic, hypnotic, and anxiolytic + hypnotic benzodiazepine users in age, history of physical illness, and previously prescribed medication. Tertiary Study : 44 long-term benzodiazepine users were interviewed. The incidence of psychological ill-health and social problems was lower than expected. Patients were dependent on medication, and reported concern if their medication were to be stopped. Nevertheless 40% considered stopping benzodiazepines. Results from the above studies are discussed in relation to clinical management of GAD, and current concerns about benzodiazepine dependence and withdrawal.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Thesis (M.A.)--Carleton University, 2000. / Includes bibliographical references. Also available in electronic format on the Internet.

A desregulação glutamatérgica parece ter uma importante participação na neurofisiopatologia da esquizofrenia, principalmente através da disfunção do receptor NMDA. A Memantina, uma droga aprovada pelo FDA para o tratamento da doença de Alzheimer de grau moderado a severo age como um antagonista fraco e não seletivo dos receptores NMDA. O objetivo deste estudo é examinar a eficácia da memantina como tratamento adjuvante à clozapina em pacientes com esquizofrenia refratária. Métodos: Em ensaio randomizado duplo cego controlado com placebo, pacientes com esquizofrenia refratária segundo os critérios do DSM-IV foram alocados aleatoriamente de março de 2005 à fevereiro de 2008 para receber 20mg/dia de memantina (n=10) ou placebo (n=11) juntamente com o tratamento padrão de clozapina. O desfecho principal analisado foi o escore total da Brief Psychiatry Rating Scale (BPRS), e suas subdivisões de sintomas positivos e sintomas negativos. Medidas secundárias observadas foram feitas através das escalas: Clinical Global Impression (CGI), cognition assessed by the Mini-Mental State Exam (MMSE), e Extrapyramidal Symptoms by the Simpson-Angus Scale (SAS). Resultados: Vinte e um participantes concluíram o estudo, e foram incluídos na análise estatística. Foi observado melhora significativa (p<0.01) na pontuação total da BPRS e suas subescalas de sintomas positivos [ES -1.38], sintomas negativos [ES -3.33], além da CGI [ES 1.56] e MMSE. Não foram observadas alterações na escala de sintomas extrapiramidais. Conclusões: A memantina como terapia adjuvante ao tratamento com clozapina em pacientes com esquizofrenia refratária está associada com melhora nos sintomas positivos e negativos Estudos que repliquem estes dados em amostras maiores e com diferentes populações são necessários para confirmar e ampliar nossos resultados. (Trial Register, clinicaltrials.gov, NCT00757978). / Background: Glutamate deregulation may be involved in the neuropathology of schizophrenia, mainly through N-methyl-d-aspartate receptor (NMDA) dysfunction. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease acts as weak non-selective NMDA receptor antagonist. The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to clozapine in patients with refractory schizophrenia. Methods: In this double-blind, placebo-controlled study, outpatients with refractory schizophrenia according DSM-IV clinical criteria were randomized from March, 2005 to February, 2008, to receive either 20 mg/day memantine (n=10) or placebo (n=11), in addition to clozapine, for 12 weeks. The primary outcome measure was the total score on the Brief Psychiatry Rating Scale (BPRS), and its subscales of positive and negative symptoms. Secondary outcomes were global severity of disease as measured by the Clinical Global Impression (CGI), cognition assessed by the Mini-Mental State Exam (MMSE), and extrapyramidal symptoms by the Simpson-Angus Scale (SAS). Results: Twenty-one participants completed the study, and were used in the analysis. Significant improvement (p<0.01) on the total BPRS score, its subscales of positive [effect size (ES) -1.38] and negative symptoms (ES –3.33), the CGI (ES size 1.56) and MMSE were observed with memantine as compared with placebo. No significant changes in extrapyramidal symptoms were observed. Conclusions: Memantine add-on to clozapine therapy was associated with improvement in negative and positive symptoms in refractory schizophrenia patients (Trial Register, clinicaltrials.gov, NCT00757978).

A double-blind comparison was conducted using typical doses of soporific agents from three drug classes and a placebo. Drugs which were used in the study included secobarbital, flurazepam hydrochloride, and thioridazine. Subjects were 40 outpatient volunteers whose primary complaint was difficulty in falling to sleep. Subjects were randomly assigned to one of the three drug groups or the placebo group. One of the drugs or the placebo was administered to each subject for 3 nights. Half of the subjects in each of the four groups were told the drug had caused any observed changes in their sleep behavior and were in this way led to attribute any changed sleep behavior externally to the drug. The other half were told the drugs were not typically used to treat insomnia and changes in their sleep were due to changes made in their own behavior, thus attributing any changes in sleep behavior internally. The implication for clinicians was that a short course of drug therapy using a placebo or one of several soporific drugs might be used equally effectively to treat primary latency insomnia. Additionally, the results demonstrated that clinicians might expect the effectiveness of treatment to be maintained following treatment. Recommendations included a suggestion for future research with soporific drugs in other classes.

A desregulação glutamatérgica parece ter uma importante participação na neurofisiopatologia da esquizofrenia, principalmente através da disfunção do receptor NMDA. A Memantina, uma droga aprovada pelo FDA para o tratamento da doença de Alzheimer de grau moderado a severo age como um antagonista fraco e não seletivo dos receptores NMDA. O objetivo deste estudo é examinar a eficácia da memantina como tratamento adjuvante à clozapina em pacientes com esquizofrenia refratária. Métodos: Em ensaio randomizado duplo cego controlado com placebo, pacientes com esquizofrenia refratária segundo os critérios do DSM-IV foram alocados aleatoriamente de março de 2005 à fevereiro de 2008 para receber 20mg/dia de memantina (n=10) ou placebo (n=11) juntamente com o tratamento padrão de clozapina. O desfecho principal analisado foi o escore total da Brief Psychiatry Rating Scale (BPRS), e suas subdivisões de sintomas positivos e sintomas negativos. Medidas secundárias observadas foram feitas através das escalas: Clinical Global Impression (CGI), cognition assessed by the Mini-Mental State Exam (MMSE), e Extrapyramidal Symptoms by the Simpson-Angus Scale (SAS). Resultados: Vinte e um participantes concluíram o estudo, e foram incluídos na análise estatística. Foi observado melhora significativa (p<0.01) na pontuação total da BPRS e suas subescalas de sintomas positivos [ES -1.38], sintomas negativos [ES -3.33], além da CGI [ES 1.56] e MMSE. Não foram observadas alterações na escala de sintomas extrapiramidais. Conclusões: A memantina como terapia adjuvante ao tratamento com clozapina em pacientes com esquizofrenia refratária está associada com melhora nos sintomas positivos e negativos Estudos que repliquem estes dados em amostras maiores e com diferentes populações são necessários para confirmar e ampliar nossos resultados. (Trial Register, clinicaltrials.gov, NCT00757978). / Background: Glutamate deregulation may be involved in the neuropathology of schizophrenia, mainly through N-methyl-d-aspartate receptor (NMDA) dysfunction. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease acts as weak non-selective NMDA receptor antagonist. The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to clozapine in patients with refractory schizophrenia. Methods: In this double-blind, placebo-controlled study, outpatients with refractory schizophrenia according DSM-IV clinical criteria were randomized from March, 2005 to February, 2008, to receive either 20 mg/day memantine (n=10) or placebo (n=11), in addition to clozapine, for 12 weeks. The primary outcome measure was the total score on the Brief Psychiatry Rating Scale (BPRS), and its subscales of positive and negative symptoms. Secondary outcomes were global severity of disease as measured by the Clinical Global Impression (CGI), cognition assessed by the Mini-Mental State Exam (MMSE), and extrapyramidal symptoms by the Simpson-Angus Scale (SAS). Results: Twenty-one participants completed the study, and were used in the analysis. Significant improvement (p<0.01) on the total BPRS score, its subscales of positive [effect size (ES) -1.38] and negative symptoms (ES –3.33), the CGI (ES size 1.56) and MMSE were observed with memantine as compared with placebo. No significant changes in extrapyramidal symptoms were observed. Conclusions: Memantine add-on to clozapine therapy was associated with improvement in negative and positive symptoms in refractory schizophrenia patients (Trial Register, clinicaltrials.gov, NCT00757978).

Introdução: O traumatismo cranioencefálico (TCE) caracteriza-se por ser uma lesão não degenerativa e não congênita e que é provocado por uma força mecânica externa. Espera-se um prejuízo, permanente ou temporário, nas funções cognitiva, física e psicossocial, com diminuição ou alteração do estado de consciência. As consequências residuais pós-TCE acometem de forma diferente cada paciente. A maioria das pessoas que sofrem traumas leves tem um processo de recuperação sem grandes complicações, e são capazes de retornar às suas atividades pré-trauma. Entretanto, a maioria dos pacientes que sofrem de TCE moderado e grave apresentam sequelas e limitações. Uma das opções medicamentosas vigentes e descritas em relatos de casos são os inibidores de acetilcolinesterase que mostram benefícios significativos quanto a melhora atencional e principalmente da memória quando utilizados em paciente na fase crônica pós TCE. Objetivo: Investigar a eficácia da rivastigmina em pacientes com comprometimento cognitivo crônico após o TCE. Métodos: Foi realizado um estudo duplo-cego, controlado com placebo em pacientes com TCE. Catorze pacientes com TCE (sete que tomaram o remédio ativo e sete que tomaram placebo) entre 18 e 70 anos completaram o estudo. Os pacientes foram randomizados em dois grupos, para receber rivastgmina ou placebo. Utilizou-se para análise dos dados comparativos entre grupo medicamento e placebo, análise estatística Z escore, teste T, qui-quadrado, correlação com o EEG e teste de correlação. Resultados: Observou-se que os pacientes que receberam a rivastigmina apresentaram melhora nos testes Cubos, BAI e memória visual de evocação imediata. No entanto, estas diferenças não foram estatisticamente significativas pelos padrões usualmente utilizados em trabalhos da área médica (alfa de 5%). Conclusão: Os resultados obtidos em pacientes com TCE apontam uma tendência que o tratamento medicamentoso com rivastigmina (medicação anti-colinesterásica) pode favorecer a estabilização ou resultar até mesmo em melhora dos déficits cognitivos, emocionais e funcionais. São necessários mais estudos com número maior de pacientes para aprofundarmos os achados aqui encontrados / Introduction: Traumatic brain injury (TBI) is characterized by a nondegenerative and non-congenital injury and is caused by an external mechanical force. Permanent or temporary impairment is expected in cognitive, physical and psychosocial functions, with a decrease or alteration of the state of consciousness. The residual consequences after TBI affect each patient differently. Most people who suffer mild trauma have a recovery process without major complications and are able to return to their pre-trauma activities. However, most patients suffering from moderate and severe TBI have sequelae and limitations. One of the current and described drug options in case reports are acetylcholinesterase inhibitors that show significant benefits in terms of attentional and especially memory improvement when used in patients in the chronic phase after TBI. Objective: To investigate the efficacy of rivastigmine in patients with chronic cognitive impairment after TBI. Methods: A double-blind, placebo-controlled study was performed in patients with TBI. Fourteen patients with TBI (seven who took the active drug and seven who took placebo) between 18 and 70 years completed the study. Patients were randomized into two groups to receive rivastgmin or placebo. To analyze the comparative data between drug group and placebo, statistical analysis Z score, T test, chi-square, correlation with the EEG and correlation test were used. Results: It was observed that the patients who received rivastigmine presented improvement in the Cubus, BAI and visual memory of immediate recall. However, these differences were not statistically significant by the standards commonly used in medical papers (5% alpha). Conclusion: The results obtained in patients with TBI point to a tendency that drug therapy with rivastigmine (anti-cholinesterase medication) may favor stabilization or even result in improvement of cognitive, emotional and functional deficits. Further studies with a larger number of patients are needed to deepen the findings found here