Tony Cohn, MD

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This article provides the rationale for monitoring parameters in patients who are being treated with antipsychotics.

At the end of this CE activity, participants should be able to:

1. Recognize the importance of metabolic monitoring.

2. Describe what the goals and challenges are of monitoring patients.

3. Describe who, when, and how to monitor.

This continuing medical education activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve their care for patients with mental health disorders.

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The focus on metabolic conditions in serious mental illness dates from the switch to atypical antipsychotics starting in the late 1990s. Metabolic conditions may include type 2 diabetes mellitus, hyperlipidemia, weight gain, obesity, metabolic syndrome, and associated coronary heart disease. The rationale for monitoring metabolic parameters during the course of antipsychotic treatment is clear.

• Reduced life expectancy in serious mental illness because of metabolic comorbidity (obesity, type 2 diabetes mellitus, dyslipidemia, coronary heart disease)

• Contemporary antipsychotics have prominent metabolic adverse effects

• Increased susceptibility to metabolic disorder because of genetic (thrifty phenotype) and lifestyle (diet, physical inactivity, cigarette smoking) factors

• Individuals with serious mental illness often receive suboptimal primary and preventive health care

Metabolic adverse effects of antipsychotics have been the subject of litigation and the focus of much media attention.

 There is considerable public awareness that compels clinicians to pay attention to these issues when prescribing antipsychotics. Metabolic adverse effects have clearly overtaken neurological adverse effects as a major concern in treating psychosis. As clinicians, we need to incorporate metabolic monitoring into clinical practice and to understand the significance of metabolic changes that develop during antipsychotic treatment.

While there has been agreement about the importance of metabolic monitoring for close to a decade, practice audits consistently show low rates of adherence to monitoring guidelines. In a recent international review of guideline-concordant monitoring for metabolic risk in patients treated with antipsychotics, adherence was “concerningly low” in routine clinical practice.

Monitoring rates remained low even after the widespread introduction of local and national guidelines starting from 2004. In a comparison of pre- and post-guideline practices, only glucose monitoring showed a statistically significant incremental increase.

The reasons for low monitoring tend to be system-related. For example, is monitoring the responsibility of the psychiatrist or of a primary care physician? Mental health practitioners may not be up-to-date or comfortable assessing and interpreting metabolic parameters. Patients with serious mental illness may not have access to primary care and may not follow through with laboratory testing or medical appointments. What action should be taken when laboratory test results are abnormal? Clinicians are busy and, thus, often systematic metabolic monitoring is not completed or sustained during the course of treatment.

One of the most concerning consequences of this is that clinical decisions are based on limited data. For example, a patient is found to have diabetes well into the course of antipsychotic treatment. The antipsychotic is switched and the patient decompensates. Without systematic monitoring, it is unclear how long the patient has had diabetes and what the relationship was to the prescribed antipsychotic. Or, clozapine is not prescribed for a diabetic patient with refractory psychosis because the clinician is convinced that there will be further weight gain and worsening of diabetes. With careful metabolic monitoring, this may well not be the case, and if there is worsening glucose control, diabetes medication can be easily adjusted.

• Early identification of treatable metabolic conditions (diabetes, dyslipidemia, and hypertension)

• Identification of individuals at high risk for metabolic disorder (metabolic syndrome, prediabetes, severe obesity) for prevention and health promotion initiatives

• Evaluation of the association between prescribed antipsychotic medication and the development of metabolic disorder by collecting systematic clinical data

• Evaluation of the outcome of metabolic interventions (antipsychotic switching, pharmacotherapy, and psychotherapy)

In North America, the key metabolic monitoring guideline is the American Diabetes Association (ADA)/American Psychiatric Association (APA) consensus document that quickly became the standard reference soon after its publication in 2004.

 The guideline specifies baseline and interval monitoring of glucose and lipid parameters and a review of the patient’s medical history and physical measurements, including weight, waist circumference, and blood pressure. In 2010, the ADA added hemoglobin A1c as a diagnostic test for diabetes, which facilitates diabetes screening because overnight fasting is not required for this test. Obtaining fasting blood samples can be challenging when working with patients who have a serious mental illness. Moreover, monitoring lipid parameters annually is preferable to every 5 years, as suggested in the original guidelines. These modifications are included in 

Other international guidelines include the position paper of the European Psychiatric Association, supported by the European Association for the Study of Diabetes and the European Society of Cardiology.

 Similar guidelines have also been developed in Australia, Canada, France, and Sweden.

 There is considerable consensus across the monitoring guidelines. Special guidelines have also been developed for monitoring metabolic changes in children and adolescents treated with antipsychotics.

Baseline monitoring is particularly important when an antipsychotic is first prescribed and when patients are switched to an antipsychotic with high metabolic liability, such as clozapine or olanzapine. This establishes a baseline from which to evaluate subsequent changes in metabolic parameters. Monitoring 3 months after the initial baseline is valuable in assessing early metabolic change.

Young, antipsychotic-naive patients are particularly susceptible to rapid weight gain.

 Change in body weight and an increase in triglyceride levels are the usual early metabolic changes; fasting glucose and hemoglobin A1c levels generally remain low initially because of compensatory hyperinsulinemia.

 Rising insulin levels can be a useful marker of early metabolic change, but insulin levels are not measured routinely because assays are not well standardized and because costs can be prohibitive.

 Occasionally, acute onset of diabetes can be picked up at the 3-month point; this is a clear indication for discontinuing or switching the antipsychotic.

Antipsychotics are prescribed long-term. Therefore, establishing a routine of annual metabolic monitoring is important so that metabolic changes can be tracked and dealt with as they arise throughout the course of treatment.

There is debate about who should be responsible for metabolic monitoring. Because mental health practitioners are often the primary health care contacts for patients with serious mental illness, it may be that the responsibility for metabolic monitoring, but not necessarily treatment of metabolic disturbance, rests with mental health practitioners. At the same time, experience has shown that systems and structures need to be established to support routine monitoring. In practice, basic psychiatric care may need to be augmented by physical health clinics and/or metabolic clinics as well as by regular audits to ensure adherence with guidelines and appropriate follow-through.

At the same time, the responsibility for monitoring oversight remains in the realm of mental health, and a basic “metabolic knowledge base” needs to be developed. In practical terms, mental health practitioners should know:

• Criteria for identifying those at risk for metabolic disturbance (

In primary and general medical practice, the relevance and importance of metabolic syndrome as a construct and as a risk marker are often debated. Guidelines for the management of hyperlipidemia are grounded on the Framingham assessment, which is based on total and low-density lipoprotein cholesterol levels. Moreover, 4 of the 5 metabolic syndrome criteria-metabolic dyslipidemia (raised triglyceride and low high-density lipoprotein cholesterol levels), abdominal adiposity (increased waist circumference), and dysglycemia (increased glucose levels)-are markers of antipsychotic metabolic effects.

 Not surprisingly, rates of metabolic syndrome are consistently elevated in adult samples of patients with serious mental illness, and fasting insulin levels (equivalent to metabolic syndrome) are elevated in younger patients with early psychosis.

 Therefore, it can be argued that metabolic syndrome has added relevance as a risk marker for patients treated with antipsychotics, an issue often not recognized by primary care providers.

In terms of equipment, practitioners should have a digital scale, blood pressure cuff, and tape measure easily accessible in the office. Office scales only measure up to 300 or 350 lb; clinics or hospitals should ensure access to a more advanced scale for patients who weigh more. Practitioners may find it useful to designate 1 month of every 6 or 12 months to focus on metabolic monitoring and to ensure that every patient in the caseload is monitored.

It helps to define the population. Many will define this as any patient who is taking regularly prescribed antipsychotics. Some would also include those receiving mood stabilizers or antidepressants because these drugs are associated with weight gain. If there is a need to focus on a smaller target, one might choose the highest-risk groups-patients with early psychosis, those receiving clozapine who are already having routine blood work, forensic patients who are confined for long periods in hospitals or jails, or high-risk ethnic groups (Hispanic, South Asian, Aboriginal, or black).

It is best to start immediately and monitor patients who have not been monitored recently. Baseline monitoring is important when an antipsychotic is first prescribed for a new patient; it will be extremely valuable if problems later emerge. When a patient’s medication is switched, particularly to a high-liability agent, getting another baseline is again valuable. Setting up reminders or a system for annual monitoring is important, as is checking 3 months after the initial baseline. More frequent monitoring is usually unnecessary and redundant unless there is a specific clinical focus or concern.

This might present the biggest challenge. There is a need for data collection, data entry, and documentation. In our center, we have developed an electronic tool that organizes these tasks, integrates with the laboratory system, analyzes the data, and flags areas of concern.

 Computer systems are well suited to this task and allow for auditing and reports. Paper-based tracking records are also used. The task of data collection and data entry can be delegated, but the prescribing clinician should maintain responsibility for ensuring that the monitoring is completed and for reviewing results.

This involves collaboration with primary care providers and other clinicians. Referrals must be made when there is a new diagnosis of diabetes, hypertension, or significant dyslipidemia or when diabetes is poorly controlled. Patients will need support to follow through with appointments and treatment. When uncertain, clinicians may find it helpful to fax results to the primary care physician or to consult a colleague. When high-risk patients are identified (prediabetes, metabolic syndrome, severe obesity), referral to a dietitian or metabolic clinic is indicated.

Dr Cohn is Assistant Professor of Psychiatry at the University of Toronto in Ontario.

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Articles

In this CME article, the focus is on the significance of metabolic changes that develop during antipsychotic treatment, as well as on strategies to incorporate metabolic monitoring into clinical practice. 

Tony Cohn, MD

Articles

Metabolic Monitoring for Patients on Antipsychotic Medications