12February2010
Posted by Jessi Kirk under: Articles of interest.
January 6, 2010 (Updated January 7, 2010) — When it comes to monitoring metabolic effects of second-
generation antipsychotics (SGAs), it appears that physicians are not heeding recommendations by government or
leading professional organizations. New research suggests that less than one-third of patients treated with these
medications, which can have significant and serious adverse metabolic effects, undergo blood glucose or lipid
testing.
“We studied a 3 state population of Medicaid recipients and found diabetes and dyslipidemia screening among
patients receiving SGAs was low and did not increase following the FDA [Food and Drug Administration] warnings or
recommendations from the American Diabetes and American Psychiatric Associations, which called for increased
metabolic monitoring of patients taking these agents,” study investigator Elaine H. Morrato, DrPH, MPH, University
of Colorado, Denver, told Medscape Psychiatry.
The retrospective analysis is published in the January issue of Archives of General Psychiatry.
Prompted by research showing a strong link between SGAs and an increased risk for hyperglycemia and diabetes,
starting in 2003 the FDA began requiring warning labels on SGAs, including olanzapine, risperidone, quetiapine,
ziprasidone, clozapine and aripriprazole.
“In some cases the hyperglycemia was extreme and associated with ketoacidosis, hyperosmolar coma, or death,”
the study authors note.
As part of the FDA initiative, manufacturers of SGAs were required to send letters to neuropsychiatric health care
professionals informing them of the warnings and advising them of the need for glucose testing in patients with a
diagnosis of diabetes, risk factors for diabetes, or symptoms of hyperglycemia.
At the same time, the American Diabetes Association and the American Psychiatric Association published a
consensus statement describing the metabolic risks associated with atypical antipsychotics and specifying a
monitoring protocol for all patients receiving these medications.
Low Rates of Metabolic Testing
To assess the impact of these warnings and recommendations on glucose and lipid testing and drug selection of
SGAs, the investigators examined laboratory claims data from the Medicaid population of 3 states — California,
Missouri, and Oregon — between 2002 and 2005.
They compared rates of metabolic monitoring between a group of 109,451 patients receiving SGAs and a control
group of 203,527 patients who began taking albuterol but who did not receive antipsychotic medication. Rates were
also compared before and after the FDA warning.
Baseline glucose and lipid testing rates for SGA-treated patients were low at 27% and 10%, respectively. However,
the FDA warning was not associated with an increase in glucose testing among SGA-treated patients, and lipid
testing rates only increased by a marginal 1.7%.
FROM: Medscape Medical News
BY: Caroline Cassels
12February2010
Posted by Jessi Kirk under: Articles of interest.
Background:
Disturbances in lipid homeostasis and myelination have been proposed in the pathophysiology of
schizophrenia and bipolar disorder. We have previously shown that several antipsychotic and antidepressant drugs
increase lipid biosynthesis through activation of the Sterol Regulatory Element-Binding Protein (SREBP)
transcription factors, which control the expression of numerous genes involved in fatty acid and cholesterol
biosynthesis. The aim of the present proof-of-principle study was to investigate whether such drugs also affect lipid
transport and export pathways in cultured human CNS and liver cells.
Results:
Quantitative PCR and immunoblotting were used to determine the level of lipid transport genes in human
glioblastoma (GaMg) exposed to clozapine, olanzapine, haloperidol or imipramine. The effect of some of these
drugs was also investigated in human astrocytoma (CCF-STTG1), neuroblastoma (SH-SY5Y) and hepatocellular
carcinoma (HepG2) cells. We found significant transcriptional changes of cholesterol transport genes (ApoE,
ABCA1, NPC1, NPC2, NPC1L1), which are predominantly controlled by the Liver X receptor (LXR) transcription
factor. The up-regulation was observed after 24 to 48 hours of drug exposure, which is markedly delayed as
compared to the drug-induced SREBP-controlled stimulation of lipid biosynthesis seen after 6 hours.
Conclusion: Our data show that stimulation of cellular lipid biosynthesis by amphiphilic psychotropic drugs is
followed by a transcriptional activation of cholesterol transport and efflux pathways. Such effects may be relevant for
both therapeutic effects and metabolic adverse effects of psychotropic drugs.
Background
Antipsychotic and antidepressant drugs are imperative in the treatment of schizophrenia and affective disorders.
These drugs exert their therapeutic effects at least in part through perturbation of the dopamine-, noradrenaline- and
serotonin neurotransmitter systems in the brain, but additional molecular mechanisms of action are likely to
contribute to their clinical effect. We have demonstrated that several antipsychotics and antidepressants increase
lipid biosynthesis in cultured human CNS cells.[1–4] This drug-induced stimulation of cellular lipogenesis could
represent a novel mechanism of psychotropic drug action in the brain, since glia-produced lipids, including
cholesterol, play important roles in myelination and synaptogenesis.[5,6] Interestingly, several studies have indicated
disrupted glial function, as well as lipid and myelin abnormalities, in schizophrenia and affective disorders.[7–11] The
drug-mediated lipogenic effect could also be relevant for the associated serious metabolic adverse effects, such as
weight gain and dyslipidemia. Indeed, some of the psychotropic drugs increase the expression of lipid biosynthesis
genes in cultured hepatocytes and adipocytes,[1,3,12–14] as well as in blood cells from olanzapine-treated patients.[15]
The increased lipid biosynthesis is mediated through activation of the sterol regulatory element-binding protein
(SREBP) transcription factors, which control the expression of genes involved in cellular production of cholesterol
(e.g., 3-hydroxy-3-methylglutaryl-CoA reductase; HMGCR) and fatty acids (e.g., fatty acid synthase; FASN and
stearoyl CoA-desaturase; SCD). The SREBP system is sensitive to cationic amphiphilic drugs, such as antipsychotic
and tricyclic antidepressant, through their ability to partly mimic the effects of oxysterols.[16]
FROM: BMC Pharmacology
By: Audun O Vik-Mo; Johan Fernø; Silje Skrede; Vidar M Steen
12February2010
Posted by Jessi Kirk under: Articles of interest.
Objective.
To develop international guidance for improving the quality of mental health care in low- and middle-
income countries.
Design.
A panel developed recommendations based on a comprehensive literature review, consultation with over
100 experts from 46 countries and an analysis of international best practices.
Recommendations. A 5-pronged approach to improving the quality of mental health care is recommended. Quality
improvement requires the alignment of policy and legislation with the attainment of good quality mental health
outcomes. Key partners must be brought into the quality improvement process. Funding can be an important tool for
promoting good quality but needs to be correctly aligned to meet policy objectives and to promote evidence-based
interventions. Accreditation procedures and quality standards need to be carefully developed and resources
allocated for their implementation. Finally, quality improvement must be brought into routine service management
and delivery.
Conclusions.
Through a systematic approach to quality improvement, it is possible to ensure that the best possible
interventions are provided within the constraints of each country and that the rights and well-being of people with
mental disorders is optimally promoted. Quality improvement is not a luxury but an integral part of ensuring that the
best possible services are provided to all who need them.
Introduction
Poor quality mental health services can violate basic human rights, lead to negative therapeutic outcomes and
prevent people from enjoying the highest standard of physical and mental health.[1] However, poor quality of care
can be substantially redressed through concerted and systematic quality improvement strategies.[2] Evidence is now
emerging that the very substantial burden of disease attributable to mental disorder can be significantly reduced
through high-quality evidence-based mental health care.[3] While prescribing methods for improving the quality of
mental health services is challenging, not least because there is tremendous variation in the availability of financial
and human resources in different countries, providing guidance to countries to assist them to attain better quality
mental health care is necessary and important.
What is Meant by Quality?
Quality in health care has been defined by the Institute of Medicine as ‘the degree to which health care services for
individuals and populations increase the likelihood of desired health outcomes and are consistent with current
professional knowledge’.[4] Quality may be viewed from a number of perspectives. For a person with a mental
disorder, quality can mean reduction in symptoms, being able to carry on with ‘normal’ life and being treated with
dignity and with full respect of his/her rights to autonomy and independent decision-making. From the point of view
of a family member, quality may mean being provided with support to help cope with some of the emotional
consequences of having an ill family member and being provided with the information and skills to actively assist a
family member’s integration into the community. A service provider on the other hand may see quality as ensuring
that patients receive the best treatment and care available. For a policy-maker, quality can be seen as the key to
improving the mental health of the population, ensuring value for money expended and accountability. All of these
perspectives are important; in this article, we primarily examine quality from the perspective of public health service
FROM: International Journal for the Quality of Health Care
By: M. Funk; C. Lund; M. Freeman; N. Drew
10February2010
Posted by Jessi Kirk under: Articles of interest.
This article is breaking and important news. Sabine Bahn the British researcher who developed the test has been working on this test and been featured in news article for some time. The partner who is commercializing the test is Rules Based Medicine. They have recently been hiring high level executives from pharmaceutical companies with expertise in marketing to market this product. Rules Based Medicine is also in the midst of becoming a publicly traded company and issuing stock to raise money for this and other bio marker tests they are working on. Although this article mentions only schizophrenia they are also working on one for Bipolar as well.
Medical News Today
Submitted by: Darrell H.
10February2010
Posted by Jessi Kirk under: Articles of interest.
The following is a link to a study on how well doctors followed up on an FDA warning about monitoring patients for side effects of atypical antipsychotics. It found that little changed in treatment practices after the warning was issued.
Science Daily
Submitted by: Darrell H.
10February2010
Posted by Jessi Kirk under: Articles of interest.
Below is a follow up article from the New York Times about last weeks big news story that antidepressants are not effective for mild depression. It notes that there is a lot more to the story than was covered by the news media last week.
New York Times
Submitted by: Darrell H. –with thanks to a friend from his emailing list
10February2010
Posted by Jessi Kirk under: Articles of interest.
The following is an article from the Wall Street Journal about antidepressants.
Wall Street Journal
Submitted by: Darrell H.
10February2010
Posted by Jessi Kirk under: Articles of interest.
The following is a link to a New Hampshire Public Radio program on brain cells known as glia or the brain’s glue.
These cells represent about 85% of the tissue in the brain and recent research has shown they have a significant role in brain function. The program mentions briefly impacts on dementia, alzheimers, schizophrenia, depression, and addiction. To listen to the program click on one of the links after listen at the upper left of the web page. The program lasts approximately 10 minutes.
New Hampshire Public Radio
Submitted by: Darrell H.
10February2010
Posted by Jessi Kirk under: Articles of interest.
The following links to an article about a study of prescribing practices by psychiatrists. It shows that Polypharmacy (using combinations of medications) is growing significantly for treatment of depression. The article also expresses concern that there is no evidence base to support this.
MedPage Today
Submitted by: Darrell H.
10February2010
Posted by Jessi Kirk under: Articles of interest.
A summary of what recent research has shown about the genetics of addiction.
Genome Web
Submitted by: Darrell H.
