Psychiatrists Urged to Pay More Heed To Patients' Physical Health
Psychiatrists and mental health professionals must change their standard of care to include physical health monitoring that typically occurs only in primary care settings. For patients with schizophrenia who do not have access to primary medical care, additional monitoring should be aimed at earlier detection of and intervention for common, serious risk factors that could lead to significant deterioration in patients' physical well-being.
Those are just two of the conclusions from a consensus conference of experts in the care and treatment of patients with schizophrenia. The conference, held at Mount Sinai School of Medicine in New York City in late 2002, produced a long list of recommendations that cumulatively amount to a significant “change in usual practice” (Psychiatric News, March 5).
The recommendations were published in the August American Journal of Psychiatry, with Stephen Marder, M.D., a professor of psychiatry at the University of California at Los Angeles and the Department of Veterans Affairs Greater Los Angeles Healthcare System, as the lead author.
Both the conference and the article were funded by Mount Sinai, the University of Texas, and several divisions of the U.S. Department of Veterans Affairs. No funding was received from the pharmaceutical industry; however, most of the conference attendees reported that they have received support from various pharmaceutical companies, mostly in the form of research grants.
The publication of the Mt. Sinai recommendations follows the release in February of the recommendations of the Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes, which was sponsored by the American Diabetes Association, APA, American Association of Clinical Endocrinologists, and North American Association for the Study of Obesity.
While the consensus conference focused primarily on metabolic dysfunction associated with the second-generation antipsychotics (SGAs), the Mount Sinai recommendations are much broader, including not only recommendations on monitoring for weight gain and glucose dysregulation that could be precursors to diabetes, but also extensive information on hyperlipidemia, QT interval prolongation, prolactin elevations and sexual dysfunction, extrapyramidal side effects and tardive dyskinesia, cataracts, and elevated risk of myocarditis in patients taking clozapine (Clozaril).
The Mount Sinai recommendations were promulgated after an extensive review of the literature on each of the treatment-emergent adverse effects associated with antipsychotic therapy. Not only was the evidence in each area reviewed, but because “the quality of available evidence for the association of specific antipsychotics with particular side effects varied considerably,” the evidence was rated as well, the authors explained.
“Level 1 evidence” included multiple, randomized, controlled trials. Data from cohort studies, outcomes research, or low-quality randomized, controlled studies were considered level 2 evidence, and data from case-control studies were considered level 3 evidence.
The guidelines and recommendations from the conference were developed to apply to care of adults with schizophrenia. Specialty populations, including the elderly, children and adolescents, and those with HIV, were not discussed.
With respect to the risk of weight gain and obesity associated with antipsychotic therapy, the consensus recommendations say there is level 1 evidence to support a “continuum of weight gain liability among the second-generation antipsychotics.”
Ziprasidone (Geodon) is associated with the lowest risk, while risperidone (Risperdal) was judged medium risk. Olanzapine (Zyprexa) and clozapine were rated high risk for weight gain, while quetiapine (Seroquel) has been associated with variable weight gain. The authors agreed, however, that quetiapine's weight gain risk “is likely to be similar to that of risperidone.” At the time of the conference, there was little evidence upon which to rate aripiprazole (Abilify).
All patients on antipsychotic therapy should have weight and body mass index (BMI) measured at regular intervals. The recommendations note that weight gain liability is an appropriate point of consideration when choosing antipsychotic therapy and emphasize that any weight gain of one (or more) BMI units indicates a need for intervention to prevent further weight gain and its complications.
The most serious of those complications—diabetes—should be closely monitored with a fasting plasma glucose or hemoglobin A1c levels measured prior to initiating a new antipsychotic medication and then at regular intervals throughout medication therapy. In addition, mental health professionals must become familiar with early signs and symptoms of diabetes, including weight loss, polyuria, and polydipsia.
Cardiac Risks Detailed
“As a group, individuals with schizophrenia should be considered at high risk for coronary heart disease,” the recommendations conclude, and should have lipid profiles monitored regularly. The new guidelines recommend that any patient with a low density lipoprotein (LDL) level greater than 130 mg/dl be referred to primary care or an internist for dietary modification and potential lipid-lowering medications.
Patients who have known cardiac disease or a history of syncope or whose family history includes sudden death before age 40 should not be prescribed an agent that prolongs the QTc interval, including older drugs like thioridazine or pimozide or the newer ziprasidone. All patients should have a baseline electrocardiogram recorded, and for those taking a QTc prolonging medication, ECGs should be monitored regularly.
The recommendations address the risk of myocarditis associated with clozapine. Both case reports and postmarketing surveillance have identified at least 30 cases of myocarditis, including 17 fatalities among 205,493 patients prescribed clozapine in the U.S. Symptoms include unexplained fatigue, dyspnea, tachypnea, fever, chest pain, palpitations, and signs of congestive heart failure.
Over 80 percent of reported cases have occurred in the first six weeks of clozapine therapy. In patients with these symptoms, myocarditis should be suspected, and a white blood cell count and plasma troponin level measured. Patients with myocarditis should be urgently referred to cardiology.
Other Symptoms to Look For
Patients should be questioned about symptoms signaling prolactin elevation, including changes in menstruation or libido and milk discharge from breasts for women, and change in libido or erectile or ejaculatory dysfunction in men. Patients who are on medications known to elevate prolactin and develop symptoms should have their prolactin level measured and any other medical causes of the symptoms ruled out. Consideration should be given, the recommendations advise, to switching a symptomatic patient with an elevated prolactin to an antipsychotic that is not associated with elevation in prolactin.
All patients must be regularly monitored for developing extrapyramidal symptoms, including examination for rigidity, tremor, and akathisia. Baseline exams should be performed to rule out parkinsonism or involuntary movement disorder, and patients at high risk should be monitored frequently throughout medication therapy.
The development of cataracts has been associated with older phenothiazine antipsychotics such as chlorpromazine and prochlorperazine. More recently quetiapine studies with animals revealed that the drug significantly increased the incidence of cataract development in dogs given high doses of the medication.
Patients who report a gradual decline in vision or an increase in blurring of their vision should be referred to an eye-care professional for a slit-lamp examination.
“Adhering to the recommendations of this conference,” the authors wrote, “will result in a significant change in the role of psychiatrists and other mental health care providers involved in the prescribing of antipsychotic medications for patients with schizophrenia.”
The conference participants “recognize that their recommendations may differ substantially from current standards of practice.”
The authors concluded, “Implementing these recommendations will take planning and the support of payers and administrators, as well as the cooperation of providers.”
An abstract of “Physical Health Monitoring of Patients With Schizophrenia” is posted online at<http://ajp.psychiatryonline.org/cgi/content/full/161/8/1334?>.▪
Am J Psychiatry 2004 161 1334
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Published online: 17 September 2004
Published in print: September 17, 2004
Notes
An exhaustive review of the evidence yields far-ranging recommendations for patients on antipsychotic therapy. The new recommendations emphasize monitoring for developing medical complications.
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