Trends in Healthcare Resource Use Preceding Diagnosis of Alzheimer's Disease Dementia.

Introduction: An Alzheimer's disease (AD) dementia diagnosis is often preceded by an extended period of cognitive decline. Few studies have examined healthcare resource use (HRU) during an extended period before AD dementia diagnosis. Methods: In a historical claims-based cohort study, propensity score-matched cohorts of patients with and without AD dementia were observed for a 5-year prediagnosis period and a 1-year postdiagnosis period. Demographics, clinical characteristics, and HRU were compared between groups. Results: Individuals in the AD dementia group displayed a greater level of medical complexity in the year before diagnosis of AD dementia relative to those in the matched cohort. Both all-cause and AD dementia complication-related HRU increased gradually, with a marked spike at the time of initial AD dementia diagnosis. Discussion. Further research into the natural history of patients with AD dementia is necessary to improve identification of early AD and to better understand its broader impact.

Gantenerumab: an anti-amyloid monoclonal antibody with potential disease-modifying effects in early Alzheimer's disease.

BACKGROUND: This review describes the research and development process of gantenerumab, a fully human anti-amyloid monoclonal antibody in development to treat early symptomatic and asymptomatic Alzheimer's disease (AD). Anti-amyloid monoclonal antibodies can substantially reverse amyloid plaque pathology and may modify the course of the disease by slowing or stopping its clinical progression. Several molecules targeting amyloid have failed in clinical development due to drug-related factors (e.g., treatment-limiting adverse events, low potency, poor brain penetration), study design/methodological issues (e.g., disease stage, lack of AD pathology confirmation), and other factors. The US Food and Drug Administration's approval of aducanumab, an anti-amyloid monoclonal antibody as the first potential disease-modifying therapy for AD, signaled the value of more than 20 years of drug development, adding to the available therapies the first nominal success since cholinesterase inhibitors and memantine were approved. BODY: Here, we review over 2 decades of gantenerumab development in the context of scientific discoveries in the broader AD field. Key learnings from the field were incorporated into the gantenerumab phase 3 program, including confirmed amyloid positivity as an entry criterion, an enriched clinical trial population to ensure measurable clinical decline, data-driven exposure-response models to inform a safe and efficacious dosing regimen, and the use of several blood-based biomarkers. Subcutaneous formulation for more pragmatic implementation was prioritized as a key feature from the beginning of the gantenerumab development program. CONCLUSION: The results from the gantenerumab phase 3 programs are expected by the end of 2022 and will add critical information to the collective knowledge on the search for effective AD treatments.

Meaningful benefits: a framework to assess disease-modifying therapies in preclinical and early Alzheimer's disease.

BACKGROUND: The need for preventive therapies that interrupt the progression of Alzheimer's disease (AD) before the onset of symptoms or when symptoms are emerging is urgent and has spurred the ongoing development of disease-modifying therapies (DMTs) in preclinical and early AD (mild cognitive impairment [MCI] to mild dementia). Assessing the meaningfulness of what are likely small initial treatment effects in these earlier stages of the AD patho-clinical disease continuum is a major challenge and warrants further consideration. BODY: To accommodate a shift towards earlier intervention in AD, we propose meaningful benefits as a new umbrella concept that encapsulates the spectrum of potentially desirable outcomes that may be demonstrated in clinical trials and other studies across the AD continuum, with an emphasis on preclinical AD and early AD (i.e., MCI due to AD and mild AD dementia). The meaningful benefits framework applies to data collection, assessment, and communication across three dimensions: (1) multidimensional clinical outcome assessments (COAs) including not only core disease outcomes related to cognition and function but also patient- and caregiver-reported outcomes, health and economic outcomes, and neuropsychiatric symptoms; (2) complementary analyses that help contextualize and expand the understanding of COA-based assessments, such as number-needed-to-treat or time-to-event analyses; and (3) assessment of both cumulative benefit and predictive benefit, where early changes on cognitive, functional, or biomarker assessments predict longer-term clinical benefit. CONCLUSION: The concept of meaningful benefits emphasizes the importance of multidimensional reporting of clinical trial data while, conceptually, it advances our understanding of treatment effects in preclinical AD and mild cognitive impairment due to AD. We propose that such an approach will help bridge the gap between the emergence of DMTs and their clinical use, particularly now that a DMT is available for patients diagnosed with MCI due to AD and mild AD dementia.

Weight gain management in patients with schizophrenia during treatment with olanzapine in association with nizatidine

OBJECTIVE: Weight gain is associated with treatment with many psychotropic agents. Nizatidine, H2 receptor antagonist, has been proposed to have weight-reducing effects. This was a 12-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of nizatidine in reducing/limiting weight gain in patients with schizophrenia who have been under treatment with olanzapine. METHOD: Patients receiving olanzapine (2 to 6 months) and weight gain > 5 percent of their body weight during olanzapine treatment were randomly assigned to receive nizatidine 600 mg or placebo for up to 12 weeks. Change in psychopathology was assessed using Brief Psychiatric Rating Scale scores from baseline to endpoint. Safety was assessed using the Safety Assessed Software, assessment of glucose and lipid blood levels, and treatment-emergent adverse events. RESULTS: Out of 54 patients enrolled in this analysis, 45 completed the protocol. The mean weight change prior randomization was 7.6 kg and 7.3 kg for those randomized to placebo and nizatidine, respectively (p = 0.828). Patients receiving placebo and nizatidine had a mean weight gain of 12.3 percent (0.7 kg) and 12 percent (1.1 kg) from baseline to endpoint, respectively (p = 0.9). Patients from both groups experienced a statistically significant decrease on the Brief Psychiatric Rating Scale mean score from baseline to endpoint. Treatment-emergent adverse events were reported by 18.5 percent and 25.9 percent on the placebo and nizatidine group, respectively. There were no statistically significant differences in glucose and lipid blood levels from baseline to endpoint and between groups. CONCLUSIONS: The concomitant use of olanzapine with nizatidine was not effective in controlling weight gain in patients who had previously gained weight during treatment with olanzapine when compared to placebo.

OBJETIVO: Ganho de peso está associado ao tratamento com inúmeros psicotrópicos. O uso de nizatidina, um antagonista H2, pode estar associado à redução de peso. Este foi um ensaio clínico aleatorizado, duplo-cego, controlado com placebo, de 12 semanas, desenhado para avaliar a eficácia da nizatidina em reduzir/limitar o ganho de peso em pacientes com esquizofrenia recebendo olanzapina. MÉTODO: Pacientes recebendo olanzapina (entre dois e seis meses) e com ganho de peso > que 5 por cento desde o inicio do tratamento foram aleatorizados para receber nizatidina 600 mg ou placebo. Alterações psicopatológicas foram avaliadas usando-se a Brief Psychiatric Rating Scale total. A segurança foi avaliada por meio da pontuação na Safety Assessed Software, avaliação dos valores de glicemia e lipídios e a incidência de eventos adversos decorrentes do tratamento. RESULTADOS: Dos 54 pacientes incluídos na análise, 45 completaram o protocolo. A alteração média de peso antes da aleatorização foi de 7,6 kg e 7,3 kg nos pacientes aleatorizados para placebo e nizatidina, respectivamente (p = 0,828). Pacientes recebendo placebo e nizatidina tiveram, respectivamente, ganho médio de peso de 12,3 por cento (7 kg) e 12 por cento (1,1 kg) ao longo do estudo (p = 0,9). Ambos os grupos apresentaram diminuição estatisticamente significativa na pontuação média da Brief Psychiatric Rating Scale. Eventos adversos emergentes do tratamento foram relatados por 18,5 por cento e 25,9 por cento dos pacientes recebendo placebo e nizatidina, respectivamente. Não houve diferença estatisticamente significativa nos níveis glicêmicos e lipídicos do início ao final do estudo ou entre os grupos de tratamento. CONCLUSÕES: Comparado ao placebo, o uso concomitante de olanzapina e nizatidina não foi eficaz em controlar o peso em pacientes com ganho prévio de peso durante o tratamento com olanzapina.

Weight gain management in patients with schizophrenia during treatment with olanzapine in association with nizatidine.

OBJECTIVE: Weight gain is associated with treatment with many psychotropic agents. Nizatidine, H2 receptor antagonist, has been proposed to have weight-reducing effects. This was a 12-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of nizatidine in reducing/limiting weight gain in patients with schizophrenia who have been under treatment with olanzapine. METHOD: Patients receiving olanzapine (2 to 6 months) and weight gain >or= 5% of their body weight during olanzapine treatment were randomly assigned to receive nizatidine 600 mg or placebo for up to 12 weeks. Change in psychopathology was assessed using Brief Psychiatric Rating Scale scores from baseline to endpoint. Safety was assessed using the Safety Assessed Software, assessment of glucose and lipid blood levels, and treatment-emergent adverse events. RESULTS: Out of 54 patients enrolled in this analysis, 45 completed the protocol. The mean weight change prior randomization was 7.6 kg and 7.3 kg for those randomized to placebo and nizatidine, respectively (p = 0.828). Patients receiving placebo and nizatidine had a mean weight gain of 12.3% (0.7 kg) and 12% (1.1 kg) from baseline to endpoint, respectively (p = 0.9). Patients from both groups experienced a statistically significant decrease on the Brief Psychiatric Rating Scale mean score from baseline to endpoint. Treatment-emergent adverse events were reported by 18.5% and 25.9% on the placebo and nizatidine group, respectively. There were no statistically significant differences in glucose and lipid blood levels from baseline to endpoint and between groups. CONCLUSIONS: The concomitant use of olanzapine with nizatidine was not effective in controlling weight gain in patients who had previously gained weight during treatment with olanzapine when compared to placebo.

[Functional status and quality of life in Latin American outpatients with schizophrenia treated with atypical or typical antipsychotics: outcomes of the 12 months schizophrenia outpatient health outcomes (IC-SOHO) Study]. / Estado funcional y calidad de vida en pacientes latinoamericanos con esquizofrenia tratados con un antipsicótico atípico o típico: resultado de 12 meses del estudio Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO).

OBJECTIVE: Functional status and quality of life outcomes in Latin American outpatients with schizophrenia were compared after 12 months of monotherapy treatment with olanzapine, risperidone or typical antipsychotics. METHOD: Both outcomes were assessed as part of a prospective, large (N= 7658), international (27 countries), observational study. RESULTS: from the Latin American subpopulation (N= 2671; 11 countries) are presented. Compared to typical antipsychotics, olanzapine and risperidone were associated with significantly (p < 0.05) greater odds of employment and social activity, and significantly greater improvements in quality of life. Olanzapine was also associated with significantly greater odds of living independently, compared to typical antipsychotics. CONCLUSION: This study indicates that functional status and quality of life outcomes are likely to be more favorable when Latin American outpatients with schizophrenia are treated with olanzapine or risperidone monotherapy, rather than typical antipsychotics.

Response and relapse in patients with schizophrenia treated with olanzapine, risperidone, quetiapine, or haloperidol: 12-month follow-up of the Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study.

OBJECTIVE: The primary aim of this study was to compare the effectiveness of 12 months' treatment with olanzapine, risperidone, quetiapine, or haloperidol in preventing relapse of schizophrenia. The study also examined other measures of clinical effectiveness and tolerability. METHOD: Outpatients with schizophrenia (ICD-10 or DSM-IV), who initiated or changed antipsychotic treatment, entered this 3-year, naturalistic, prospective, observational study between November 2000 and December 2001. At baseline, subsets of patients were prescribed monotherapy with olanzapine (N = 3222), risperidone (N = 1116), quetiapine (N = 189), or haloperidol (N = 256). Patients remaining on monotherapy were assessed using the Clinical Global Impression-Schizophrenia scale. Relapse rate was determined from the responder subset. Treatment patterns, patient perception of treatment compliance, substance and alcohol intake patterns, and treatment tolerability were recorded. Results are based on 12-month treatment data. RESULTS: Compared to haloperidol-treated patients, olanzapine- and risperidone-treated patients had approximately 3 to 4 times higher odds of response at 12 months (p

[Latin America: clinical responses to the antipsychotic drugs]. / América Latina: respuesta a los antipsicóticos.

OBJECTIVE: To compare the effectiveness of a 12 months antipsychotic monotherapy treatment with Olanzapine, risperidone and an atypical antipsychotic drug in Latin American patients with schizophrenia. METHOD: The outcomes of effectiveness and tolerability were evaluated in outpatients with schizophrenia belonging to a large sample (N=7658) in a prospective, international trial carried out in 27 countries. The results for the population of Latin America were presented. RESULTS: The probabilities of response were higher for Olanzapine than Risperidone and the atypical antipsychotic drugs. (p < or = 0.05) and for risperidone compared with the atypical antipsychotic drugs. (p < or = 0.05). Olanzapine was better tolerated as regarding the extrapiramidals symptoms and the sexual disfunction, although it was associated to a higher weight gain, as compared to the other groups of the trial. CONCLUSION: the trial indicated that in the Latin American patients with schizophrenia, it is likely that Olanzapine induces clinical responses and has lower incidences on side effects, when compared with risperidone or atypical antipsychotic drugs.

Impacto da comorbidade no diagnóstico e tratamento do transtorno bipolar / Impact of the comorbidity in the diagnosis and treament of bipolar disorder

Os autores descrevem as principais comorbidades em pacientes com transtorno bipolar e suas implicações no diagnóstico e tratamento. A presença de comorbidades dificulta o diagnóstico e o manejo clínico do paciente e está associada à pior resposta ao tratamento. Dada a grande freqüência da comorbidade de transtorno bipolar com transtornos de ansiedade, é obrigatória sua pesquisa em pacientes bipolares. O tratamento do paciente bipolar com comorbidade quase sempre envolve a utilização de um estabilizador do humor. Com base nos dados de literatura não é possível dizer que um seja melhor que outro em pacientes com transtorno bipolar e comorbidade com outro transtorno. Quando se faz necessário o uso de antidepressivos há cuidados e riscos que devem ser lembrados. Os benzodiazepínicos podem ser úteis como coadjuvantes na farmacoterapia desses pacientes.

Exercício físico excessivo e transtornos alimentares / Physical exercise and eating disorders

A atividade física traz benefícios para a saúde mas em excesso pode ser prejudicial. Este estudo procurou avaliar se indivíduos com exercício excessivo (EFEx) se assemelham àqueles com transtorno alimentar (TA) em relação a comportamentos alimentares e imagem corporal. Foram avaliados 50 pacientes com TA com e sem EFEx e 69 sujeitos recrutados em academias de ginástica com e sem TA e/ou com e sem EFEx. Ao contrário de nossa hipótese inicial, indivíduos com TA são significantemente diferentes daqueles com EFEx em todas as variáveis analisadas. Instrumentos mais sensíveis poderiam ser úteis para detectar alterações mais sutis porém ainda inadequadas em indivíduos com EFEx.Physical activity is related to benefits for health in general but when done in excess can also be associated with impairments. This study aimed to evaluate if subjects with excessive exercise (EEx) are similar to eating-disordered (ED) patients regarding food habits and body image. We evaluated 50 eating-disordered outpatients with/out EEx and 69 subjects from gyms with/out ED and with/out EEx. Contrary to our initial hypothesis, ED patients are significantly different from those with only EEx in all variables analyzed. The development of more sensitive tools can be useful to determine more subtle but still inadequate behaviors in excessive physical exercisers...

Dismorfia muscular / Muscle dysmorphia

Preocupações mórbidas com a imagem corporal eram tidas até recentemente como problemas eminentemente femininos. Atualmente estas preocupações também têm sido encontradas no sexo masculino. A dismorfia muscular é um subtipo do transtorno dismórfico corporal que ocorre principalmente em homens que, apesar da grande hipertrofia muscular, consideram-se pequenos e fracos. Além de estar associada a prejuízos sociais, ocupacionais, recreativos e em outras áreas do funcionamento do indivíduo, a dismorfia muscular é também um fator de risco para o abuso de esteróides anabolizantes. Este artigo aborda aspectos epidemiológicos, etiológicos e padröes clínicos da dismorfia muscular, além de tecer comentários sobre estratégias de tratamento para este transtorno

Ganho de peso e medicações antipsicóticas / Weight gain and antipsycotics

Desde sua introdução no mercado, os antipsicóticos têm sido relacionados a aumento de peso. O advento dos antipsicóticos de nova geração trouxe avanços significativos no tratamento dos quadros esquizofrênicos tanto em relação à sintomatologia negativa, depressiva e cognitiva quanto em relação à segurança e tolerabilidade. No entanto, o ganho de peso ainda se mantém como um evento adverso frequente nesta classe. As autoras apresentam um breve resumo da literatura sobre o ganho de peso associado à terapia antipsicótica e seus possíveis mecanismo de ação. Descrevem ainda estratégias cognitivo-comportamentais e farmacológicas para o manejo do ganho de peso para os pacientes em uso de medicações antipsicóticas.

Atividade fisica e transtornos alimentares / Physical activity and eating disorders

Individuos com transtornos alimentares utilizam-se de um arsenal de metodos para controle de peso, incluindo a atividade fisica excessiva, e com prejuizos fisicos, sociais e psiquiatricos. Objetivos: descrever os metodos utilizados para controle de peso, com enfase para...

Alteracoes psiquiatricas associadas ao uso de anabolizantes / Psychiatric symptoms associated with anabolic steroids

Atletas interessados em melhorar o desempenho esportivo e nao-atletas interessados em melhorar a forca fisica e a aparencia tem utilizado esteroides anabolico-androgenicos (EAA) fora de suas indicacoes medicas. Alem dos efeitos adversos em varios orgaos do corpo, estudos recentes tem demonstrado que o uso de ESS pode levar a sindromes psiquiatricas importantes, incluindo quadros maniformes, psicoticos e depressivos, principalmente quando em doses elevadas. Essa revisao procura abordar resumidamente...