In 2003, the FDA issued a warning for second-generation antipsychotics, including olanzapine and risperidone, among others, citing an increased risk for diabetes and hyperglycemia. The FDA stated that glucose levels should be monitored in patients with diabetes, at risk for diabetes or with symptoms of hyperglycemia. Concurrently, the American Diabetes Association and American Psychiatric Association recommended glucose and lipid testing for all patients started on second-generation antipsychotics.
In June 2009, a study in Diabetes Care cited evidence that adults being treated with second-generation antipsychotic (SGA) drugs, have up to two times greater prevalence of type 2 diabetes, dyslipidemia, hypertension, and obesity. Then in January 2010, the FDA issued a warning about adverse metabolic effects for patients taking the second-generation antipsychotic drug olanzapine, which is approved for the treatment of schizophrenia and bipolar disorder in adolescents and adults. At that time the manufacturer of the drug, Eli Lilly, issued a letter to prescribers, noting that after 24 weeks of treatment, the percentage of adults who gained at least 7% of their baseline body weight was 89%. The letter also noted that elevations as high as 500 mg/dL in triglycerides had been observed in adolescents taking the drug.
While it’s clear that patients taking these drugs are at risk for metabolic disorders, the question of who is responsible for monitoring for these syndromes remains. “It’s not always clear which physician is supposed to the screening, the monitoring, and the treating,” Elaine H. Morrato, DrPH, MPH, assistant professor in the department of health systems, management and policy at the University of Colorado, Denver, said in an interview. “What are the jobs of the psychiatrist, the primary-case doctor, and the referred endocrinologist?”
Metabolic Syndrome and Coordinated Care
According to a 2008 perspective published in Primary Care Companion of the Journal of Clinical Psychiatry, “primary care professionals have an important part to play in the physical health care of people with mental illness, as they are well positioned to monitor metabolic disturbances and should do so regularly,” wrote the authors of the perspective. Before any atypical drugs are prescribed, this includes the essential measurement of key indicators such as weight, waist circumference, height, plasma glucose level, blood pressure, and lipid profile. For effective long-term treatment, “careful clinical monitoring over time [should be] the standard of care in both mental and primary health care,” the researchers wrote.
For patients using community mental health centers for their primary care, screening innovations are being implemented that are having an impact. In a 2010 issue of Psychiatric Services,Christina Mangurian, MD, and colleagues noted that 4 months after the New York State Office of Mental Health mandated that all adult outpatient clinics regularly monitor their patients’ body mass index, blood pressure and smoking status, nearly half (n= 7,500) of all adult outpatients with mental illnesses being treated by the State Office of Mental Health, had been screened for these physical health indicators. “What gets measured, gets managed,” the researchers wrote.
But according a study by Corell et al, also in a 2010 issue of Psychiatric Services, there are obstacles that may keep psychiatrists from effectively monitoring their patients in accordance with published guidelines. “Among mental health providers, barriers include lack of comfort with medical issues or lack of time and resources to address [them],” the researchers wrote.
The issue is not a lack of awareness on behalf of the psychiatrist, according to Sun H. Kim, MD, an assistant professor of endocrinology, gerontology and metabolism at Stanford University School of Medicine. “Many doctors, especially psychiatrists, are aware and concerned about the side-effect profile of antipsychotic medications,” he said. Instead, Kim said the main issue is that patients who are treated with antipsychotic medications are primarily seen by psychiatrists who feel more comfortable managing psychiatric problems than metabolic ones. “Therefore, there might be some hesitancy to order these [types of monitoring] tests,” he said.
And other clinicians cite the responsibilities and workload that come with being in a smaller versus larger practice. “[The notion of a community health center] is great, [particularly if you can] consolidate records, and integrate,” said Morrato. “But how do you address the needs of the private practice, which might be a sole practitioner whose office is not set up to be doing this type of monitoring?”
An Innovative Treatment Model
One option, said Morrato, is for private mental health practitioners to rely on a health fair model such as one cited in the study by Correll and colleagues. Held simultaneously at 219 sites across the United States, this 1-day, voluntary metabolic health screening service, sponsored by Pfizer, Inc., was utilized by 10,084 mental health patients from a variety of mental health facilities, including public clinics and group practices. The service offered same-day feedback to physicians by a biometrics testing third party in accordance with the Health Insurance Portability and Accountability Act.
Results of the fair supported the prevalence of metabolic adverse effects in patients with schizophrenia and bipolar disorders. These were due both to lifestyle influences as well as the use of second-generation antipsychotics. Overall, the mean waist circumference of the screened patients was 41.1 inches for men and 40.4 inches for women. Body mass indices showed that 27% of all participants were overweight (Body mass index [BMI] of 25.0–29.9 kg/m2); 52% were obese (BMI ≥ 30.0 kg/m2); 51% had elevated triglycerides (≥150 mg/dl); and 51% were hypertensive (≥ 130/85 mm Hg).
Nearly a third (n = 2,739) of patients reported having fasted for 8 hours or more before prior to the screening. In this cohort, 52% had metabolic syndrome; 35% had elevated total cholesterol (≥200 mg/dl); and 59% had low levels of high-density lipoprotein cholesterol (<40 mg/dl for men, (<50 mg/ dl for women); 45% had elevated triglycerides (≥150 mg/dl); and 33% had elevated fasting glucose (≥100 mg/dl). Of the fasting patients with metabolic syndrome (n = 1,359), 60% reported receiving no treatment. Schizophrenia or bipolar disorder was self-reported by 62% of participants overall.
According to Morrato, the health fair model is a strategy that small practices who might have difficulty coordinating this kind of care can outsource, similar to when cardiologists rely on health screening services to monitor their patients on blood thinners. “It takes the burden off the specialist,” she said.
Switching to Drugs Associated With Less Risk
One way around the issue of how to treat patients with bipolar and other mood disorders without increasing their risk for metabolic syndrome is to switch prescriptions. Results of a survey of 298 psychiatrists, published in Current Medical Research and Opinion, indicated that providers concerned about the connection between compliance and weight gain in their patients with bipolar disorder to whom they had prescribed second-generation antipsychotics changed their patients’ prescriptions, although they also added monitoring to their treatment regimens.
In the survey, nearly all respondents (96%) reported a 20 lb increase in their patients’ weight as an adverse event associated with certain agents. Overall, clozapine and olanzapine were the agents consistently viewed as most likely to cause significant weight gain and other metabolic concerns. After changing their patients’ medications, more than 80% of respondents then monitored their patients’ weights, fasting plasma glucose levels, and fasting lipid profiles at regular intervals.
“A growing recognition of the differences in weight-gain potential and adverse metabolic effects among agents appears to have had a definite impact on prescribing patterns in the management of bipolar disorder,” the authors wrote. “Since most patients receive long-term treatment, clinically significant weight gain … may cause them to discontinue their medication and this may lead to relapse.”
Morrato, Hartung, et al analyzed rates of diabetes and dyslipidemia screenings in Medicaid laboratory claims made in California, Oregon and Missouri between 2002 and 2005 — before and after the 2003 FDA warning. The investigators compared glucose and lipid monitoring trends in 109,451 patients receiving second-generation antipsychotics to 203,527 patients taking albuterol for asthma, but not antipsychotics. The findings, published in the January 2010 issue of Archives of General Psychiatry, indicated that while new prescriptions for olanzapine declined during the warning period (annual share decline, 19.9%; P < .001), new prescriptions for aripiprazole (Abilify, Otsuka), which is not typically associated with metabolic issues, have increased (12.1%; P < .001).
“I suspect that it is easier, and therefore faster, to switch prescribing practices following a drug warning, particularly if safer alternatives are available, than it is to increase complexity in medical care by adding extra monitoring,” Morrato said. However, Morrato also cites data from Verispan that found that by 2009 the atypical antipsychotic drug category was #1 in the US based on dollar sales. With that evidence in mind, “I don’t [necessarily] think the metabolic warnings have caused significant switching to other drug classes,” she said.
Communication Between Specialties
Regardless of who ultimately is responsible for the screening, monitoring and management of metabolic risks associated with patients taking second-generation antipsychotics, communication between psychiatrists and endocrinologists is essential to minimizing adverse events. “Psychiatrists may not typically be trained to monitor for diabetes and endocrinologists may not typically be trained to monitor for mental health disorders,” Morrato said. “There is a pretty clear consensus that the psychiatrist is not going to manage the patient’s diabetes. For patients taking antipsychotics, it is important that both health care professionals are involved in patient care decision-making. However, unless there is well-integrated care, it can place more ownership and burden on the patient to manage information between the different specialties.”
“I would love to see a model in which patients with psychiatric problems are taken care of in a system where both psychiatric and medical issues are addressed in one clinic by a team of physicians,” Kim said.
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- Correll, C. Psychiatric Serv, 2010; 61:9. doi:10.1176/appi.ps.61.9.892 [CrossRef]
- Ketter, TA. Current Med Res Opin. 2006;22:12:2345–2353. doi:10.1185/030079906X148616 [CrossRef]
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- Morrato, EH. Arch Gen Psychiatry. 2010;67:17–24. doi:10.1001/archgenpsychiatry.2009.179 [CrossRef]
- Morrato, EH. Diabetes Care. 2009 doi: doi:10.2337/dc08-1720 [CrossRef] .
Leslie Citrome, MD, MPH
Weight gain associated with medication treatment can be a deterrent to adherence for some patients. However the amount of weight gain that is disconcerting for one individual may not be as distressing for another. Moreover, for a person who has been battling a severe and persistent mental disorder, weight gain in the context of successful control of psychosis and extreme mood swings may be an acceptable bargain. In those instances it is often the clinician who is the most worried about the consequences of being overweight and obese. In any event, true shared decision-making would require full disclosure of metabolic risks and potential premature mortality. The philosophy of evidence-based medicine1 encourages the clinician to use his/her clinical experience and judgment, together with the best available research evidence, and also take into account the individual patient’s values and preferences. All three considerations are required in order to obtain the best possible outcome for the patient in question, and attention to the patient’s values and preferences is key to adherence. Selection of a medication will be highly dependent on a person’s past history of therapeutic response and tolerability concerns, of which the latter may include divergent phenomena such as weight gain, akathisia, and somnolence/sedation. The practitioner is fortunate to have a variety of options that differ in these tolerability profiles.
Leslie Citrome, MD, MPH
Professor of Psychiatry,
New York University School of Medicine.
- Sackett, DL, Rosenberg, WMC & Gray, JAM et al. Evidence based medicine: what it is and what it isn’t. BMJ. 1996;312(7023):71–72.