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Atypical antipsychotics and metabolic testing.

Psychiatrists have long been besieged with warnings about possible connections between second-generation antipsychotics and the ripple effects of the weight gain they sometimes induce: diabetes and cardiovascular disease Cardiovascular disease
Disease that affects the heart and blood vessels.

Mentioned in: Lipoproteins Test

cardiovascular disease 

In 2003, the Food and Drug Administration imposed a label change on the drug class, warning of the risk of hyperglycemia hyperglycemia: see diabetes.  and requiring those with pre-existing diabetes or risks to be monitored.

By 2004, the American Diabetes Association, American Psychiatric Association (APA (All Points Addressable) Refers to an array (bitmapped screen, matrix, etc.) in which all bits or cells can be individually manipulated.

APA - Application Portability Architecture
), American Association of Clinical Endocrinologists, and the North American North American

named after North America.

North American blastomycosis
see North American blastomycosis.

North American cattle tick
see boophilusannulatus.
 Association for the Study of Obesity issued consensus guidelines recommending a schedule of metabolic testing (see chart) and suggesting consideration of a change in agent if weight gain rises more than 5% above baseline during treatment.

For patients with serious psychiatric illness, the risks are even more profound, said Dr. John W. Newcomer, professor of psychiatry, psychology, and medicine at Washington University in St. Louis, and the chair of an APA working group that is creating a White Paper on atypical antipsychotic drugs Antipsychotic Drugs, Atypical Definition

The atypical antipsychotic agents, sometimes called the "novel" antipsychotic agents are a group of drugs which are different chemically from the older drugs used to treat psychosis.
 and metabolic risk.

Patients with schizophrenia and bipolar disorder bipolar disorder, formerly manic-depressive disorder or manic-depression, severe mental disorder involving manic episodes that are usually accompanied by episodes of depression.  often lead unhealthy lifestyles, independent of being prescribed an atypical antipsychotic drug: Some smoke, eat poorly, and fail to get enough exercise. The life expectancy Life Expectancy

1. The age until which a person is expected to live.

2. The remaining number of years an individual is expected to live, based on IRS issued life expectancy tables.
 of seriously mentally ill patients is about 25-30 years less than mentally healthy adults, with the primary drivers of excess mortality medical causes, especially cardiovascular disease, rather than suicide.

The role of atypical antipsychotic drugs in perpetuating weight gain in this at-risk patient group has been characterized as a class-wide effect, although certain agents have been disproportionately associated with the problem. Guidelines and warnings alike stress the importance of monitoring all patients taking any second-generation antipsychotic antipsychotic /an·ti·psy·chot·ic/ (-si-kot´ik) effective in the treatment of psychotic disorders; also, an agent that so acts. Antipsychotics are a chemically diverse but pharmacologically similar class of drugs; besides psychotic  drug, and following more closely those with risk factors or changes in metabolic parameters.

"Numerous surveys of psychiatrists show a high level of awareness of the risks, a recognition of the importance of these metabolic risks, and the intention to screen. But what we see when we look at actual billing claims for the lab testing tells a different story," said Elaine H. Morrato, Dr. P. H., primary author of several studies evaluating metabolic testing rates in psychiatric patients. She holds academic appointments in the schools of public health, medicine, and pharmacy at the University of Colorado University of Colorado may refer to:
  • University of Colorado at Boulder (flagship campus)
  • University of Colorado at Colorado Springs
  • University of Colorado at Denver and Health Sciences Center
  • University of Colorado system
 School of Medicine in Denver.

In one representative example from her research, an analysis of laboratory claims data for 18,876 commercially insured adults initiating atypical antipsychotic drugs found that 23% and 8% received baseline glucose testing and lipid testing, respectively. Annual testing rates were 38% (glucose) and 23% (lipids). There were slight increases in testing compliance in the years before the 2004 consensus statement, but "the ADA statement was not associated with an increase in screening rates," the study found (Diabetes Care 2009;32:1037-42).

Patient-related barriers, clinical issues, and systemic shortfalls are all to blame, said Dr. Jayendra K. Patel, director of schizophrenia research and bipolar disorder at the Center for Psychopharmocologic Research and Treatment at the University of Massachusetts The system includes UMass Amherst, UMass Boston, UMass Dartmouth (affiliated with Cape Cod Community College), UMass Lowell, and the UMass Medical School. It also has an online school called UMassOnline. , Worcester, in an interview.

Psychiatrists may understand the metabolic risks of atypical antipsychotics in a vulnerable population and want to avoid those risks, but they have to work in a system that doesn't make it easy for them to ensure that monitoring gets done.

One shortfall is the reliance on individual psychiatrists, many of whom are unaccustomed to routinely conducting physical examinations on patients, to take patients' blood pressures, measure weights and heights, calculate BMIs, and write and follow up on laboratory orders.

In many cases, "offices are not set up that way," lacking a blood pressure cuff, a scale, or a nurse, said Dr. Morrato.

"Relying on the physician to remember when someone is due for an assessment has variable success rates,'' said Dr. Robert Marvin, medical director for the Psychosis Program at the University of Illinois at Chicago This article is about the University of Illinois at Chicago. For other uses, see University of Illinois at Chicago (disambiguation).

UIC participates in NCAA Division I Horizon League competition as the UIC Flames in several sports, most notably Basketball.
. "We have found in our clinic that it takes a systems-level approach to be successful." His team includes a psychiatric pharmacist and clinical nurse specialists who share responsibility for ensuring that patients are regularly monitored and receive appropriate referrals and care if they show signs of weight gain or altered metabolic parameters.

Ideally, such local system solutions make it easy to remember to perform or order periodic screenings, with chart checklists and tracking of results, system-wide, Dr. Morrato added.

Institutions are also taking the lead in coordinating care between psychiatrists and primary care specialists and/or pertinent specialists such as endocrinologists and cardiologists, who can either facilitate screening in conjunction with the prescribing psychiatrist, or who can serve as referral sources who can be relied upon to provide sensitive interventions to a difficult patient population.

Another core issue is the delicate risk-benefit analysis risk-benefit analysis,
n the consideration as to whether a medical or surgical procedure, particuarly a radical approach, is worth the risk to the patient compared with the possible benefits if the procedure is successful.
 that accompanies treating profoundly mentally ill patients: the target group for receipt of atypical antipsychotic medications.

Schizophrenia is a complex, chronic, debilitating mental illness that has no easy fix, Dr. Patel said. "The treatment for each patient has to be individualized, with respect to where this patient is, what he has been through, his ethnic/racial background and family medical history, and how serious his psychosis is."

Given a patient with very severe psychosis, a history of suicide Suicide has been committed by people from all walks of life since the beginning of known history. Among the famous who have taken their own lives are Socrates, Boudicca, Brutus, Mark Antony, Cleopatra VII of Egypt, Judas Iscariot, Hannibal, Nero, Virginia Woolf, Sadeq Hedayat, Sigmund  attempts, and who also has a family history of diabetes and cardiovascular disease, he said he would consider prescribing clozapine clozapine /clo·za·pine/ (klo´zah-pen) a sedative and antipsychotic agent; used in the treatment of schizophrenia.

, the atypical antipsychotic drug most closely linked to metabolic alterations. "We are always balancing competing values: the value of aggressively, successfully treating a patient to the best possible outcome [versus] avoiding side effects that might affect long-term outcome."

The question comes back to monitoring and ensuring that the risk-benefit analysis adapts to physiologic changes in the patient, he said. If a patient gains weight, it's evident, but "what a patient doesn't see is the cholesterol, the triglycerides Triglycerides
Fatty compounds synthesized from carbohydrates during the process of digestion and stored in the body's adipose (fat) tissues. High levels of triglycerides in the blood are associated with insulin resistance.
, the glucose level, the blood pressure, and these are what really hurt the patient but are not so obvious."

These silent contributors can escape the attention of a busy practitioner, particularly one who isn't in the habit of ordering screening tests and doesn't work in a system designed to facilitate that.

Even when screening is implemented, the system can fail. Not all psychiatrists have a close working relationship with a primary care physician who can follow up on laboratory values and competently treat mentally ill patients. And not all patients have the means or motivation to get to a lab and an internist's office after they've been to the psychiatrist.

Finally, there is the issue of discussing the side effects, Dr. Patel said.

The notion of avoiding certain agents to skirt the issue has become, apparently, the de facto alternative to screening for many psychiatrists. Prescribing patterns suggest "doctors made a clinical judgment that they would not need to monitor much or at all if the patient was taking a low-risk drug,'' said Dr. Newcomer.

Although it is true that there is a "huge spectrum of weight gain liability" among drugs in the class, it remains "disappointing" that physicians have failed to heed well-publicized warnings about risk in a vulnerable patient population prescribed polypharmacy, he said.

Data analyses by Dr. Morrato and Dr. Newcomer show that about 80% of the patients at the highest risk get screened, compared with about 20% of those with no risk factors cited in claims data.

However, physicians' preferential screening decisions ignore the gradation gradation: see ablaut.  effect associated with escalating risk and miss the opportunity to prevent disease by catching problems early, especially in young patients, said Dr. Morrato.

One possible solution is to carefully switch a patient from a higher- to a lower-risk alternative within the class, which-has been found to be less disruptive to the clinical course of most patients than once believed. Another is to begin with a less risky alternative, while still monitoring according to ADA guidelines.

Dr. Morrato has received research funding from Pfizer. Dr. Newcomer has received grant support and/or was a consultant to numerous pharmaceutical companies, including the makers of several drugs within the atypical antipsychotic class. Dr. Marvin said he did not have any relevant financial disclosures. Dr. Patel receives research grant support from Johnson 8c Johnson, Bristol-Myers Squibb, and Forest Pharmaceuticals.
Metabolic Workup Guidelines, Atypical Antipsychotics

Measurement            Baseline  4 Weeks  8 Weeks  12 Weeks  Quarterly

Personal/Family           X

Height/Weight/BMI *       X         X        X        X         X

Waist circumference       X

Fasting blood glucose     X                           X

Fasting lipid profile     X                           X

Blood pressure            X                           X

Measurement              Annually     Every 5 years

Personal/Family history     X

Height/Weight/BMI *

Waist circumference         X

Fasting blood glucose       X **

Fasting lipid profile                    X **
                                   (If normal in year 1)

Blood pressure              X **

* If a patient gains 5% or more of his/her initial weight at any time
during therapy, a switch in the second-generation antipsychotic should
be considered. BMI should be reassessed at 4, 8, and 12 weeks after
switching, and quarterly thereafter.

** More frequently if clinically indicated, or in those with higher
baseline risk for developing diabetes or hypertension. Source:
Consensus Development Conference on Antipsychotic Drugs and Obesity and
Diabetes, Diabetes Care

Patterns suggest doctors make a clinical judgment that patients on a low-risk drug need less monitoring.


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Author:Bates, Betsy
Publication:Clinical Psychiatry News
Date:Aug 1, 2009
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