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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients receiving treatment with atypical antipsychotics commonly experience weight gain, which can cause considerable distress and can have deleterious effects on cardiovascular health. Because of the associated weight gain and potential direct effects on glucose metabolism, atypical antipsychotics have also been linked to the development of type II diabetes mellitus. Data on long-term treatment with these agents show that clozapine and olanzapine, followed by risperidone, were associated with the greatest degree of weight gain. A large body of data suggests that during long-term treatment, patients receiving the atypical antipsychotic quetiapine experience minimal weight gain. Data also suggest that quetiapine treatment does not increase the risk of developing type II diabetes. The use of atypical antipsychotics is increasing, as these agents are being prescribed for schizophrenia in lieu of conventional antipsychotics. Furthermore, these drugs have efficacy for treating other conditions such as bipolar disorder. Physicians prescribing atypical antipsychotics must be aware of the risk of weight gain and its associated comorbidities.
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PMID:The implications of weight changes with antipsychotic treatment. 1283 46

Many antipsychotic drugs disturb the regulation of glucose metabolism in patients treated for schizophrenia. The goal of the present studies was to determine if these antipsychotic drugs produce hyperglycemia in mice in relation to their ability to interfere with glucose uptake and utilization. Male C57BL/6 mice were injected with a panel of typical and atypical antipsychotic drugs and blood glucose levels were determined periodically over a 3- to 6-h time interval. The atypical drugs, clozapine, desmethylclozapine, quetiapine, and loxapine, and the original antipsychotic, chlorpromazine, induced significant hyperglycemia in the mice in accordance with their effects on glucose transport. By contrast, haloperidol and sulpiride, which have little effect on glucose uptake, did not induce hyperglycemia. Risperidone produced a modest elevation of blood glucose levels, but only at a low dose of the drug. Cytochalasin B, a specific inhibitor of the glucose transporter (GLUT) protein, produced significant hyperglycemia in the mice. Overall, there was a strong correlation between the ability of a drug to inhibit glucose transport in vitro and its ability to induce hyperglycemia in vivo. Finally, the drugs that produced hyperglycemia in mice have been linked to the development of diabetes in patients.
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PMID:Induction of hyperglycemia in mice with atypical antipsychotic drugs that inhibit glucose uptake. 1287 13

GW Pharmaceuticals is undertaking a major research programme in the UK to develop and market distinct cannabis-based prescription medicines [THC:CBD, High THC, High CBD] in a range of medical conditions. The cannabis for this programme is grown in a secret location in the UK. It is expected that the product will be marketed in the US in late 2003. GW's cannabis-based products include selected phytocannabinoids from cannabis plants, including D9 tetrahydrocannabinol (THC) and cannabidiol (CBD). The company is investigating their use in three delivery systems, including sublingual spray, sublingual tablet and inhaled (but not smoked) dosage forms. The technology is protected by patent applications. Four different formulations are currently being investigated, including High THC, THC:CBD (narrow ratio), THC:CBD (broad ratio) and High CBD. GW is also developing a specialist security technology that will be incorporated in all its drug delivery systems. This technology allows for the recording and remote monitoring of patient usage to prevent any potential abuse of its cannabis-based medicines. GW plans to enter into agreements with other companies following phase III development, to secure the best commercialisation terms for its cannabis-based medicines. In June 2003, GW announced that exclusive commercialisation rights for the drug in the UK had been licensed to Bayer AG. The drug will be marketed under the Sativex brand name. This agreement also provides Bayer with an option to expand their license to include the European Union and certain world markets. GW was granted a clinical trial exemption certificate by the Medicines Control Agency to conduct clinical studies with cannabis-based medicines in the UK. The exemption includes investigations in the relief of pain of neurological origin and defects of neurological function in the following indications: multiple sclerosis (MS), spinal cord injury, peripheral nerve injury, central nervous system damage, neuroinvasive cancer, dystonias, cerebral vascular accident and spina bifida, as well as for the relief of pain and inflammation in rheumatoid arthritis and also pain relief in brachial plexus injury. The UK Government stated that it would be willing to amend the Misuse of Drugs Act 1971 to permit the introduction of a cannabis-based medicine. GW stated in its 2002 Annual Report that it was currently conducting five phase III trials of its cannabis derivatives, including a double-blind, placebo-controlled trial with a sublingual spray containing High THC in more than 100 patients with cancer pain in the UK. Also included is a phase III trial of THC:CBD (narrow ratio) being conducted in patients with severe pain due to brachial plexus injury, as are two more phase III trials of THC:CBD (narrow ratio) targeting spasticity and bladder dysfunction in multiple sclerosis patients. Another phase III trial of THC:CBD (narrow ratio) in patients with spinal cord injury is also being conducted. Results from the trials are expected during 2003. Three additional trials are also in the early stages of planning. These trials include a phase I trial of THC:CBD (broad ratio) in patients with inflammatory bowel disease, a phase I trial of High CBD in patients with psychotic disorders such as schizophrenia, and a preclinical trial of High CBD in various CNS disorders (including epilepsy, stroke and head injury). GW Pharmaceuticals submitted an application for approval of cannabis-based medicines to UK regulatory authorities in March 2003. Originally GW hoped to market cannabis-based prescription medicines by 2004, but is now planning for a launch in the UK towards the end of 2003. Several trials for GW's cannabis derivatives have also been completed, including four randomised, double-blind, placebo-controlled phase III clinical trials conducted in the UK. The trials were initiated by GW in April 2002, to investigate the use of a sublingual spray containing THC:CBD (narrow ratio) in the following medical conditions: pain in spinal cord injury, pain and sleep in MS and spinal cord injury, neuropathic pain in MS and general neuropathic pain (presented as allodynia). Results from these trials show that THC:CBD (narrow ratio) caused statistically significant reductions in neuropathic pain in patients with MS and other conditions. In addition, improvements in other MS symptoms were observed as well. Phase II studies of THC:CBD (narrow ratio) have also been completed in patients with MS, spinal cord injury, neuropathic pain and a small number of patients with peripheral neuropathy secondary to diabetes mellitus or AIDS. A phase II trial of THC:CBD (broad ratio) has also been completed in a small number of patients with rheumatoid arthritis, as has a trial of High CBD in patients with neurogenic symptoms. A phase II trial has also been evaluated with High THC in small numbers of patients for the treatment of perioperative pain. The phase II trials provided positive results and confirmed an excellent safety profile for cannabis-based medicines. GW Pharmaceuticals received an IND approval to commence phase II clinical trials in Canada in patients with chronic pain, multiple sclerosis and spinal cord injury in 2002. Following meetings with the US FDA, Drug Enforcement Agency (DEA), the Office for National Drug Control Policy, and National Institute for Drug Abuse, GW was granted an import license from the DEA and has imported its first cannabis extracts into the US. Preclinical research with these extracts in the US is ongoing.
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PMID:Cannabis-based medicines--GW pharmaceuticals: high CBD, high THC, medicinal cannabis--GW pharmaceuticals, THC:CBD. 1295

Diabetes or hyperglycemia associated with the use of atypical anti-psychotic agents is a subject of growing concern among health care providers and the patients who use the drugs. Although much attention has been relegated to this topic in the mental health literature, there has been little attention devoted to it in the diabetes literature. The purpose of this report is to review the problem of diabetes mellitus associated with atypical anti-psychotic use from an endocrinology perspective. This paper will specifically present (a) a review of the increased prevalence of diabetes in the setting of schizophrenia, (b) a compilation and critical assessment of the existing publications that have documented the association of hyperglycemia and atypical anti-psychotic use, (c) a discussion of the potential mechanisms through which antipsychotics may lead to disturbances in glucose homeostasis, and (d) recommendations for the effective monitoring and treatment of affected patients.
Diabetes Technol Ther 2003
PMID:Diabetes mellitus associated with atypical anti-psychotic medications. 1451 22

Plasma membranes are fluid structures and the maintenance of fluidity is a prerequisite for function, viability, growth and reproduction of cells. Membrane fluidity is the reciprocal of membrane microviscosity, which in turn is inversely proportional to rotational and lateral diffusion rates of membrane components. In the absence of constraints most lipids and unrestrained integral proteins freely diffuse in the plane of the membrane with high diffusion coefficients. The fluid mosaic model of plasma membrane structure is essentially still valid but this model is by its nature a macroscopic one. At present, attention is focused on molecular structural details of protein-lipid interactions and on the static and dynamic structure of membrane proteins. Highly potent new macroscopic and microscopic methods have been developed to measure translational diffusion of membrane lipids and proteins. The microscopic methods can reveal diffusion via encounters between labeled molecules. Fluorescence anisotropy measurements are the most widely used techniques in biological research. The use of different permeant and non-permeant fluorophores have contributed much to a better understanding of the changes in the ordered states and motional freedom of the membrane phospholipids in different cells during development, aging and physiological functions as well as in pathological conditions. The application of fluorophores with non-random distribution have shed light on the asymmetrical changes between the outer and inner domain of the lipid bilayer and on the dynamics of 'flip-flop' in signal transduction. Membrane fluidity was shown to have a decisive role in the efficiency of ligand binding, in the outcome of direct cell to cell contacts and in the modulation of the activity of membrane enzymes. Cell filtrability reflects whole cell viscosity that can not always be correlated with the fine changes in membrane fluidity. Cell viscosity depends inter alia on the size and shape of the cells as well as on membrane rigidity. In contrast to this, membrane fluidity is only dependent on the freedom of mobility of the membrane constituents. Increased release of free radicals and reactive oxygen specie (ROS) affect membrane fluidity, cellular Ca2+ homeostasis, induce lipid peroxidation and finally cell death. Investigation of membrane fluidity proved to be a useful and sensitive additional method to obtain a better insight into the mechanisms by which different compounds, drugs and contact with foreign surfaces are affecting cellular functions. The measurements of membrane fluidity may gain more widespread use for monitoring the safety and efficacy of these actions. During the last few years, changes in membrane fluidity of blood cells have been reported during development and aging and as a result of physiological cell functions. Membrane fluidity changes have been described in thrombocythaemia, hyperlipidaemia, hypercholesterolaemia, hypertension, diabetes mellitus, obesity, septic conditions and in allergic and burnt patients, in alcoholics, in Alzheimer's disease and in schizophrenia. A short summary is given on red cell membrane fluidity changes in a Hungarian triosephosphate isomerase (TPI)-deficient family, reflecting how the very subtle changes in membrane fluidity can help to establish underlying biological differences between the clinical phenotypes of a severe enzyme (TPI) deficiency caused by the defect of a single gene in two brothers one with and one without neurological symptoms.
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PMID:Membrane fluidity of blood cells. 1465 48

There is well accepted evidence that the long-term outcome of schizophrenia is better in developing than in developed countries. Socio-cultural factors, which are as yet unidentified, have been postulated to explain this. There is also disputed evidence that schizophrenia was rare in indigenous populations and increased when they came into contact with Western or industrialised cultures, and that there was an increase in the rate of schizophrenia during the Industrial Revolution. These epidemiological and historical findings point to diet as a possible mediating factor in schizophrenia. Ecological studies have indicated that a worse outcome of schizophrenia is associated with higher consumption of saturated fat and sugar. It is also known that schizophrenic patients have increased insulin resistance and are at increased risk of developing diabetes and coronary heart disease. These findings suggest a new paradigm for our understanding of the causation and treatment of schizophrenia.
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PMID:Nutrition and schizophrenia: an epidemiological and clinical perspective. 1470 54

This study compared the risks of cardiovascular morbidity and mortality in people with schizophrenia who use antipsychotic medications to risks in individuals without schizophrenia in a large managed care organization. A sample of 1920 schizophrenia patients was matched by age, sex, date, and health plan to 9600 persons randomly selected from the health plan general membership. Death, myocardial infarction, arrhythmia, and new-onset diabetes were identified using a National Death Index search and medical claims records. The adjusted all-cause mortality rate in the group of treated schizophrenics was four times higher than in the control group regardless of whether patients were given a typical or an atypical antipsychotic medication. Users of typical antipsychotics had a fivefold higher risk of myocardial infarction than the control subjects. Among patients with schizophrenia, cardiovascular risk was inversely associated with intensity of use of antipsychotic drugs, suggesting that the observed risks may not be due to a simple or direct effect of drugs. Patients treated for schizophrenia had higher rates of new-onset diabetes than did the general population controls. This risk was most pronounced in persons with more intense exposure to drugs and appeared to be indistinguishable in users of typical antipsychotics, of atypical products, or of both.
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PMID:Serious cardiovascular events and mortality among patients with schizophrenia. 1471 72

The pharmacotherapy of schizophrenia remains an ongoing challenge for researchers and clinicians alike. Current medications remain suboptimal to effectively treat this illness despite the recent surge of what are considered to be better antipsychotics: the atypicals. The atypicals cause fewer extrapyramidal symptoms and tardive dyskinesia, but there is growing concern regarding the significant long-term metabolic and cardiac adverse effects of these novel antipsychotics. There are differences among the atypicals in their propensity to produce these adverse effects, and clinicians should weigh the risk-benefit ratio for each drug with each individual patient. Diabetes, heart disease, obesity, and unhealthy lifestyle choices are on the rise in the general population, and individuals with chronic schizophrenia are even more at risk. The dilemma clinicians face in trying to avoid the neurological morbidity of the typicals (extrapyramidal side effects and tardive dyskinesia) is the risk of consequently exposing patients to both the morbidity and potential mortality of the atypicals (cardiovascular, endocrine, and metabolic adverse effects). The importance of baseline investigations and monitoring at regular intervals as well as identification of patients at risk for obesity, diabetes, and cardiovascular morbidity has become crucial. Informed decision making is essential for successful antipsychotic pharmacotherapy. For a condition, which often necessitates long-term pharmacotherapy, the importance of prevention and (or) minimization of morbidity and mortality related to adverse effects of such pharmacotherapy cannot be understated.
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PMID:From chlorpromazine to clozapine--antipsychotic adverse effects and the clinician's dilemma. 1563 57

During the last few years, several case reports and studies have been published on the potential diabetes mellitus (DM)-inducing effect of some atypical antipsychotics, especially clozapine and olanzapine. The purpose of our study was to evaluate diabetogenic effects of atypical antipsychotics in the literature. In order to give a full-scale overview, both peer-reviewed publications and oral and poster presentations on this subject were screened. We found 27 case reports of new-onset DM for clozapine, 39 for olanzapine, 4 for risperidone, and 3 for quetiapine. Related to the year of introduction of these drugs on the market and the number of treatment days of each drug during the last 6 years in 13 western countries, Brazil, and Japan, the cases show an over-representation of cases related to olanzapine and clozapine. In the majority of cases, risk factors (DM family history, obesity, Negroid ethnicity) were present. Eighty-four percent of the cases arose in patients < 50 years, in contrast to the general population (most cases, > 50 years). Comparative epidemiological studies point in the same direction, with two studies showing no differences between the atypical drugs. Antipsychotic agents are used often for treatment of schizophrenia, a condition that appears to be associated with DM also in untreated subjects. Some antipsychotics appear to induce new-onset diabetes mellitus. In view of the health risks of DM and the predisposition in patients with schizophrenia, it is advised to be cautious with prescription of antipsychotics that are associated with new-onset DM. Especially in predisposed patients (family history of DM, obese, Negroid ethnicity), reticence in this respect is required. Moreover, careful monitoring of weight, BMI, and glucose levels is advised both before these antipsychotics are prescribed and during treatment.
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PMID:Atypical antipsychotics and new onset diabetes mellitus. An overview of the literature. 1475 42

Diabetes and mental disorders are common chronic illnesses in the United States. Recently, the introduction of a new class of atypical antipsychotic medications has been a major treatment advance for patients with mental disorders. Because of increased use of atypical antipsychotic medications, new and unanticipated side effects have often appeared. Treatment-emergent diabetes has been described for conventional and atypical antipsychotics. People with schizophrenia may be at increased risk for type 2 diabetes because of the side effects of antipsychotic medication, underlying predisposition, and less healthy lifestyles.
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PMID:Hyperglycemia with antipsychotic treatment. 1476 79


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