ABSTRACT
Olanzapine has been associated with insulin resistance and new-onset diabetes mellitus. A 27-year-old African-American man developed new-onset severe hyperglycemia-glucose 1240 mg/dl, with ketonuria and acidosis, but no weight gain-2 years after starting olanzapine. Although his diabetes was stabilized with insulin, his family had difficulty monitoring his therapy, and insulin was discontinued. Subsequent monotherapy with pioglitazone stabilized the patient's glucose levels, allowing him to continue taking olanzapine. Health care professionals should be aware of links between olanzapine and diabetes mellitus and of the potential for delayed recognition of complications associated with diabetes in patients who are psychotic. Insulin poses additional problems because families of patients with schizophrenia have to deal with compliance and risk of accidental or suicidal overdose. This case and others described in the literature illustrate such dilemmas and highlight the need to further study links connecting diabetes, insulin resistance, and olanzapine. Further research to determine proportionality and risk differences among various atypical antipsychotics also is warranted.
Subject(s)
Antipsychotic Agents/adverse effects , Diabetic Ketoacidosis/chemically induced , Hyperglycemia/chemically induced , Ketone Bodies/urine , Pirenzepine/analogs & derivatives , Pirenzepine/adverse effects , Adult , Benzodiazepines , Diabetic Ketoacidosis/blood , Diabetic Ketoacidosis/complications , Humans , Hyperglycemia/blood , Hyperglycemia/complications , Male , OlanzapineABSTRACT
In this article, we primarily focus on the treatment approaches currently marketed and in advanced stages of development for Alzheimer's disease (AD). Amyloid plaques and neurofibrillary tangles remain the pathologic hallmarks of AD, and much progress has been made in unraveling the molecular biology of these changes. In addition, there is also intense research into inflammatory and oxidative mechanisms as well as vascular and neurochemical alterations in AD. Therapies targeted at these mechanisms are discussed.
Subject(s)
Alzheimer Disease/complications , Cognition Disorders/drug therapy , Cognition Disorders/etiology , Mental Health Services/trends , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antioxidants/therapeutic use , Cholinergic Agents/therapeutic use , Cholinesterase Inhibitors/therapeutic use , Cognition Disorders/diagnosis , Estrogens/therapeutic use , Forecasting , Ginkgo biloba/therapeutic use , Humans , Phytotherapy , Plants, Medicinal , Vitamin E/therapeutic useABSTRACT
Regulatory guidelines in the US and Europe generally require that a drug specifically indicated for treating Alzheimer's disease (AD) must demonstrate an effect upon the core manifestations of dementia. Progressive cognitive and functional losses are the cardinal features of AD. In the US, current guidelines require that new AD treatments show effectiveness on performance-based measures of cognition and on clinician-rated global assessments. Improvement in function is also emphasized in the European guidelines. The primary instruments that have been used to evaluate changes in cognition and global function in most recent AD trials are the cognitive subscale of the Alzheimer's Disease Assessment Scale and a version of the Clinician's Interview Based Impression of Change, respectively. The results from three pivotal trials investigating the acetylcholinesterase inhibitor, donepezil, are used to demonstrate the way in which these tools are used, how to interpret the data they provide, and to determine their overall value in ascertaining efficacy in clinical practice.
