Reducing Cardiometabolic Risk in Patients With Serious Psychiatric Illness
Patients with schizophrenia are at an inherently higher risk for cardiometabolic disease than the general population. As such, the risks of cardiometabolic side effects from antipsychotic agents are important to consider, as are lifestyle interventions. If prevention is not successful, risk factor mitigation is needed.
What is your approach to the management of cardiometabolic risk in patients with schizophrenia?
Clinical Professor of Psychiatry
“One should initially prescribe antipsychotics with the most favorable metabolic profiles. . . .”
Part of the initial approach to reducing metabolic risk is simply recognizing that patients with schizophrenia have a high number of inherent risk factors, including biologic factors such as poor glycemic control and lifestyle factors such as sedentary behavior and smoking. Patients may also have inadequate access to general medical care or are simply reluctant to see providers of nonpsychiatric care. Thus, the pattern of risk arises from a confluence of issues.
Younger, first-episode patients may also be uniquely sensitive to certain adverse effects of antipsychotic medications, particularly weight gain. It is important to make their first experience with antipsychotic medication as benign as possible so that side effects will not contribute to adherence issues. One should initially prescribe antipsychotics with the most favorable metabolic profiles and consider long-term treatment with agents that carry more metabolic risk only when patients fail to respond to more metabolically benign medications.
In terms of nonpharmacologic strategies, we should offer all patients some type of behavioral intervention to increase activity levels, as well as nutritional counseling. These interventions do not have to be sophisticated. Straightforward suggestions, such as cutting back on sugary drinks and juices, may be the initial dietary goal. Furthermore, every patient who smokes should be offered a smoking cessation treatment of some kind when they are psychiatrically stable. While this may be rejected initially, the topic should be discussed with the patient on a regular basis.
Risk mitigation strategies should be a consistent part of the clinical routine. Patients may decline to follow a certain recommended behavior modification (eg, smoking cessation); however, if treatment options are never offered, the likelihood of a patient pursuing these goals without support is low. In addition, it is important to continue mentioning such modifications, even if a patient is initially resistant, as they may change their mind at some point in the future.
In terms of a systems perspective, we should do what we can to develop models that allow patients better access to nonpsychiatric care. The co-localized model has been one of the most successful. Many community mental health centers now have an embedded primary care provider so that psychiatric patients can receive nonpsychiatric care in a place where they already feel comfortable. Clinicians should take advantage of whatever local resources are available, whether that is a co-localized or consultation model, or engaging a case manager to help the patient attend nonpsychiatric medical appointments. It is extremely important that mental health clinicians facilitate their patients receiving nonpsychiatric medical care.
“Pending newer treatments with a lower potential for metabolic adverse effects, we need to routinely use the strategies that are available to us. The first strategy with respect to prescribing involves the prevention of metabolic issues, and the second is the mitigation of those issues if you must use a drug that has caused a problem for the patient.”
I would reiterate that our patients with schizophrenia are at an inherently higher risk for cardiometabolic disease than the general population. This is due to genetic predisposition, environment, and unhealthy lifestyle. Patients with schizophrenia have much higher rates of smoking cigarettes than the general population, and smoking is considered an equivalent to having the metabolic syndrome in terms of cardiovascular risk. If a clinician can reduce or eliminate a patient’s smoking, it will have a tremendous impact on their coronary heart disease risk. I spend quite a bit of time talking about smoking with my patients with schizophrenia, and also about their lifestyle issues, including their eating and exercise habits. I weigh my patients during each office visit, and weight management is an active source of discussion. Reducing the risk of coronary heart disease is an ongoing process.
In terms of antipsychotic medication selection, patients vary as to whether they will experience a problem with tolerability or safety. I sometimes prescribe antipsychotic medications that carry a higher risk for cardiometabolic problems, and we continue with that treatment as long as the patient is tolerating it and does not exhibit rapid or excessive weight gain or alterations in their metabolic indices. However, when I prescribe an older second-generation antipsychotic and the patient gains a substantial amount of weight over a few weeks, I realize that that drug is no longer a feasible option for the patient, unless I can mitigate the weight gain with the use of medications such as metformin and/or nonpharmacologic interventions such as diet and exercise.
Pending newer treatments with a lower potential for metabolic adverse effects, we need to routinely use the strategies that are available to us. The first strategy with respect to prescribing involves the prevention of metabolic issues, and the second is the mitigation of those issues if you must use a drug that has caused a problem for the patient.
Senior Vice President, Behavioral Health Services
“ . . . patients with chronic and severe mental illness have a significantly shorter life expectancy than healthy controls. . . . It is important that effective mechanisms are in place to ensure that patients have good collaborative medical care. It is also important to help motivate patients to follow through with some of the strategies that we discussed to lower risks.”
I am not sure that we have sufficiently emphasized the fact that patients with chronic and severe mental illness have a significantly shorter life expectancy than healthy controls. There are a variety of factors that contribute to this, and we have alluded to some of them. But it is an important public health issue to try to help patients obtain better control over these issues. It is an uphill battle, but I believe that there is a lot more that we can do.
Dr Meyer mentioned that patients with schizophrenia do not always have good access to health care or want to take advantage of nonpsychiatric health care. It is important that effective mechanisms are in place to ensure that patients have good collaborative medical care. It is also important to help motivate patients to follow through with some of the strategies that we discussed to lower risks. Follow-through is hard enough for the average person, but it is even more difficult for someone with a serious mental illness.
Minimizing the risk of metabolic effects from psychotropic medications is essential. However, problematic prescribing is still common. For example, olanzapine is a very efficacious drug, but it has multiple metabolic side effects. In many situations, other antipsychotic medications would be preferable.
I wish to conclude by mentioning that there is some evidence that elevated fasting insulin levels may be associated with schizophrenia, independent of antipsychotic medication use. Even in drug-naive, first-episode patients, we see some evidence of insulin resistance. The issue of cardiometabolic risk in schizophrenia is thus quite complicated, is not necessarily due to medication therapy alone, and requires continued attention.
Cunningham JI, Eyerman DJ, Todtenkopf MS, et al. Samidorphan mitigates olanzapine-induced weight gain and metabolic dysfunction in rats and non-human primates. J Psychopharmacol. 2019;33(10):1303-1316. doi:10.1177/0269881119856850
Daumit GL, Dalcin AT, Dickerson FB, et al. Effect of a comprehensive cardiovascular risk reduction intervention in persons with serious mental illness: a randomized clinical trial. JAMA Netw Open. 2020;3(6):e207247. doi:10.1001/jamanetworkopen.2020.7247
Fleischhacker WW, Arango C, Arteel P, et al. Schizophrenia–time to commit to policy change. Schizophr Bull. 2014;40(suppl 3):S165-S194. doi:10.1093/schbul/sbu006
Guest PC. Insulin resistance in schizophrenia. Adv Exp Med Biol. 2019;1134:1-16. doi:10.1007/978-3-030-12668-1_1
Kearns B, Cooper K, Cantrell A, Thomas C. Schizophrenia treatment with second-generation antipsychotics: a multi-country comparison of the costs of cardiovascular and metabolic adverse events and weight gain. Neuropsychiatr Dis Treat. 2021;17:125-137. doi:10.2147/NDT.S282856