Metabolic Monitoring of Patients Taking Antipsychotics: Are We Doing All We Can?

When Charles Raison, MD, ran an inpatient treatment team in the early days of the atypical antipsychotics, he had a consistent warning for families of patients with psychosis—the patients would need new clothes before being discharged from the hospital.

“They would go up two or three dress sizes,” he said.

Research shows that the newer “atypical” or second-generation antipsychotic medications are associated with a host of metabolic side effects, including weight gain, dyslipidemia, and diabetes mellitus.¹ While the extent of these metabolic effects depends on the specific antipsychotic prescribed and patient-specific factors, patients in one study gained 8% to 15% of their baseline weight in 12 weeks,² and other research showed antidiabetic medication was prescribed as soon as 30 days after inpatient admission in some patients.³

Patients who experience these side effects are at risk on two levels—their physical health may deteriorate, and they might not adhere to their psychiatric medication.⁴ “Because of these risks, it’s very clear that optimal psychiatric care involves monitoring metabolic risk and side effects,” said Dr. Raison, Associate Professor at the College of Medicine and the College of Agriculture and Life Sciences at the University of Arizona in Tucson.

However, despite the risks of adverse metabolic effects and medication noncompliance, many psychiatrists believe they and their colleagues have done an inadequate job of monitoring and caring for patients’ metabolic issues.^{5, 6} “Too often, my patients report that blood work to check for metabolic syndrome is not ordered frequently enough,” said Saundra Jain, MA, PsyD, LPC, Executive Director of the Mental Aerobics Project in Lake Jackson, Texas.

Part of the problem is the fragmentation of care that is all too common in many clinical practices and the resultant tendency to assume that other health care professionals are performing the monitoring. Yet the psychiatrist, as the prescriber, should be “the nerve center” of the medical team, said Dr. Raison.

Rakesh Jain, MD, MPH, Director of Psychiatric Drug Research at the R/D Clinical Research Center in Lake Jackson, Texas, echoed this sentiment by saying psychiatrists have “the highest responsibility” for the medications they prescribe, and therefore let  their patients down when they forget that patients have minds and bodies—both of which should be monitored and treated.

The Nuts and Bolts of Monitoring

Monitoring metabolics is relatively simple, requiring only a reliable scale, measuring tape to determine waist circumference, and basic lab work. The key factor is taking the time to weigh people, said Dr. Raison. “If you don’t keep track of the numbers, you run the risk of gradually getting used to changes in the way a patient looks, and it’s easy to lose track of how much weight they’ve gained,” he said. “But it’s important not just to rely on weighing patients, because antipsychotics can negatively impact metabolic function over and above the effect on weight, and you’ll miss this if you don’t also check patients’ blood.”

Dr. Rakesh Jain and Dr. Raison strongly recommend referring to the 2004 American Psychiatric Association (APA) and American Diabetes Association (ADA) guidelines for specifics on how to monitor patients from baseline onward.⁷ According to the guidelines, baseline measurements should include personal and family history, weight and height to calculate BMI, waist circumference, blood pressure, fasting plasma glucose, and fasting lipid profile.

Follow-up monitoring of the patient’s weight should be conducted at 4, 8, and 12 weeks after the initiation of or changes to pharmacotherapy, as well as quarterly during routine visits. Three months after initiation of antipsychotics, the psychiatrist should check patients’ fasting plasma glucose, lipid levels, and blood pressure.

An Efficient System

In Dr. Raison’s experience, clinicians who devise an efficient system are more likely to reliably monitor their patients. Psychiatrists practicing in hospital settings may have easy access to a lab and an in-house system, but clinicians in private practices and other settings may need to develop their own procedures. Dr. Raison offers several strategies:

• Put in the time up front to create an efficient, well-thought-out monitoring system and ensure it evolves into a routine. This saves time and makes metabolic monitoring less likely to be forgotten in the midst of a busy day.
• Make everything easy for the patient: pick a lab close to the office, obtain any requisition forms ahead of time, and place a stack of the forms next to maps of the lab’s location.
• Involve other staff members. Your nurse can give instructions to patients, and administrative staff members can offer directions or distribute maps.

Dr. Raison emphasized the importance of “making the collection and monitoring of metabolically important data brain-dead and reliable. You’re going to be doing it a gazillion times, so this reduces the temptation to get sloppy.”

Clues to a Problem

According to the 2010 ADA guidelines for prediabetes, patients with a fasting glucose level of 100 to 125 mg/dL, an oral glucose tolerance test result of 140 to 199 mg/dL, or a hemoglobin A(1c) of 5.7% to 6.4% are classified as prediabetic.⁸

The 2004 APA and ADA guidelines recommend immediate care for patients with:

• symptomatic or severe hyperglycemia
• symptomatic hypoglycemia
• glucose levels of 60 mg/dL or less, even if symptoms are not present.

However, the guidelines caution that treatment and goals should be individualized and considered in the context of the patient’s psychiatric condition and treatment.

In addition, early and significant weight gain often signals that a patient is experiencing metabolic effects. “If you put somebody on a new drug and they come back a month or two  later and have gained eight or nine pounds, that’s someone who’s likely to gain a lot of weight,” noted Dr. Raison.

Intervention

Once a problem is identified, patients should become part of the conversation around treating metabolic effects. “It can be difficult; it becomes my job to tell them you cannot ignore your body,” said Dr. Rakesh Jain. Often, he will call upon family members to persuade the patient to make dietary changes, since even minor adjustments help. “A shift to diet soda from regular soda can be incredibly powerful,” he added.

Dr. Saundra Jain frequently treats patients dealing with weight gain, including teaching them how to use a food and exercise log to manage their weight.

However, if nonpharmacologic interventions are not effective, the psychiatrist might choose to treat metabolic issues with appropriate agents or switch antipsychotic medications.

According to Dr. Raison, making such a medication decision is complex and highly tailored to each patient, because the benefits of switching to an agent with an improved metabolic profile must be balanced against the potential risks of losing clinical effect and inducing other types of side effects that a patient may find intolerable. It is also important to emphasize that individuals have hugely different metabolic responses to the same agent. Nonetheless, a number of studies suggest that several of the newer antipsychotics, including ziprasidone, asenapine, lurasidone and aripiprazole, may be options for some patients.^{9, 10}

Dr. Raison and Dr. Rakesh Jain agree that the best way to maximize the possibility of success with any intervention is to catch metabolic problems as soon as possible. Early intervention—before metabolic syndrome or diabetes develops—maximizes the chance of reducing weight gain. Once a patient gains 100 lbs, it becomes difficult to exercise, said Dr. Rakesh Jain.

In the future, advances in genetics may lead to testing that gauges which patients will experience extreme weight gain.^{11, 12} For example, researchers have recently shown that antipsychotic-induced weight gain is tightly linked to the ability of some of these agents to impact insulin production via effects on the SMAD3 protein. Agents that impact SMAD3 induce metabolic abnormalities, while antipsychotics without this effect do not. This raises the possibility that researchers may eventually develop antipsychotic medications  that retain positive neurological effects without negative metabolic side effects.¹³

For now, though, “the way to know is to be watching. When the patient starts gaining weight and showing worrisome metabolic trends in their lab values, that’s when you know,” advised Dr. Raison.

Dr. Rakesh Jain strongly believes that psychiatrists must embrace this vital responsibility if they are not doing so already. “It’s time to be honest with each other and look at the large, nasty skeleton that hangs in our closet—that we simply don’t monitor patient’s bodies as much as we should. It’s time to fix it.”

—Lauren LeBano

References

1. McEvoy JP, Meyer JM, Goff DC, et al. Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr Res. 2005;80(1):19-32.
2. Correll CU, Manu P, Olshanskiy V, et al. Cardiometabolic Risk of Second-Generation Antipsychotic Medications During First-Time Use in Children and Adolescents. JAMA. 2009;302(16):1765-1773.
3. Citrome L, Jaffe A, Levine J, et al. Relationship between antipsychotic medication treatment and new cases of diabetes among psychiatric inpatients. Psychiatr Serv. 2004;55(9):1006-1013.
4. DiBonaventura MD, Gabriel S, Duplclay L, et al. A patient perspective of the impact of medication side effects on adherence: Results of a cross-sectional nationwide survey of patients with schizophrenia. BMC Psychiatry. 2012;12(20): 1471-244X.
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6. Mitchell AJ, Delaffon V, Vancampfort D, et al. Guideline concordant monitoring of metabolic risk in people treated with antipsychotic medication: systematic review and meta-analysis of screening practices. Psychol Med. 2012;42(1):125-147.
7. American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; et al. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27(2):596-601.
8. American Diabetes Association. Standards of Medical Care in Diabetes—2010. Diabetes Care. 2010;33 Suppl 1:S11-61. 
9. Citrome, L. Lurasidone in schizophrenia: new information about dosage and place in therapy. Adv Ther. 2012;29(10):815-825.
10. Chen Y, Bobo WV, Watts K, et al. Comparative effectiveness of switching antipsychotic drug treatment to aripiprazole or ziprasidone for improving metabolic profile and atherogenic dyslipidemia: a 12-month, prospective, open-label study. J Psychopharmacol. 2012;26(9).:1201-1210.
11. Adkins DE, Aberg K, McClay JL, et al. Genomewide pharmacogenomics study of metabolic side effects to antipsychotic drugs. Mol Psychiatry. 2011;16(3):321-322.
12. Malhotra AK, Correll CU, Chowdhury NI, et al. Association between common variants near the melanocortin 4 receptor gene and severe antipsychotic drug-induced weight gain. Arch Gen Psychiatry. 2012;69(9):904-912.
13. Cohen T, Sundaresh S, Levine. Antipsychotics activate the TGFβ pathway effector SMAD3. Mol Psychiatry. 2012 Jan 31;186.