Rapid Rise in Cardiometabolic Risk in Early Schizophrenia

Fran Lowry

October 14, 2014

Patients with first-episode schizophrenia spectrum disorders (FES) develop cardiometabolic risk factors and abnormalities that manifest within weeks of illness onset, new research suggests.

Dr Christoph Correll

This rapid increase in cardiometabolic risk is likely related to a combined effect of the underlying illness, unhealthy lifestyle, and antipsychotic medications, the authors, led by Christoph U. Correll, MD, of the North Shore–Long Island Jewish Health System and the Zucker Hillside Hospital, Glen Oaks, New York, note.

"Patients with early-phase schizophrenia spectrum disorders already have a lot of cardiometabolic risk indicators and risk factors that have accumulated, even over a short period of treatment with antipsychotics, 47 days on average," Dr Correll told Medscape Medical News.

"This is something we need to pay attention to as clinicians, so that we do the appropriate monitoring and interventions. I would hope that our study results help clinicians become more attuned to these difficulties, and also help their patients make safer choices regarding a healthier lifestyle," Dr Correll added.

The study was published online October 8 in JAMA Psychiatry.

High Morbidity, Mortality

It is well known that individuals with schizophrenia have high cardiovascular morbidity and mortality, but their risk status and the mediators or moderators of risk in the earliest stages of illness are less clear.

In the current study, the investigators analyzed baseline results from the Recovery After an Initial Schizophrenia Episode–Early Treatment Program (RAISE-ETP) study, which included 394 patients who had suffered an initial schizophrenia episode. The data were collected between July 2010 and July 2012 from 34 community mental health centers.

Patients were aged 15 to 40 years (mean age, 23.6 years) and had received fewer than 6 months of antipsychotic treatment (mean lifetime antipsychotic treatment, 47.3 days).

The investigators looked at patients' body composition and fasting lipid, glucose, and insulin levels.

Nearly half of the patients (48.3%) were obese or overweight. The mean body mass index was 26.6 (standard deviation, 6.7). Half (50.8%) of the patients smoked; 56.5% had dyslipidemia; 40% had prehypertension; 10% had hypertension; and 13% had metabolic syndrome.

Of the patients who had dyslipidemia, only 0.5% received lipid-lowering medication, and of the patients who had hypertension, only 3.6% received antihypertensive medication.

Of the study patients, prediabetes was present in 4%, as determined on the basis of glucose measurement, and in 15.4%, as determined on the basis of hemoglobin A1C measurement. Diabetes was present in 3% (glucose based) and in 2.9% (hemoglobin A1C based).

The duration of psychiatric illness was significantly correlated with higher body mass index, fat mass, fat percentage, and waist circumference (P < .01 for all measures). However, duration of illness was not correlated with elevated metabolic parameters, with the exception of triglycerides-to-HDL-C ratio (P = .04).

On the other hand, duration of antipsychotic treatment was significantly correlated with higher non-HDL-C levels, higher triglyceride levels, and higher triglycerides-to-HDL-C ratio and lower HDL-C levels and systolic blood pressure (P ≤ .01 for all measures).

Two antipsychotic drugs were particularly associated with metabolic impairment ― olanzapine (multiple brands) and quetiapine (Seroquel, AstraZeneca Pharmaceuticals LP).

Olanzapine was significantly associated with higher triglyceride levels, higher insulin levels, and insulin resistance (P ≤ .02), and quetiapine was associated with significantly higher triglycerides-to-HDL-C ratio (P ≤ .02).

"We know from other studies that aripiprazole [Abilify, Otsuka Pharmaceuticals Co, Ltd], lurasidone [Latuda, Sunovion Pharmaceuticals, Inc], and ziprasidone [Geodon, Pfizer Inc] are lower risk for cardiometabolic abnormalities and should be preferred, particularly early on in treatment," Dr Correll said.

"We have guidelines in the United States that say that Zyprexa (olanzapine) should be second-line, and still many first-episode patients receive it. I think that should stop. There is no evidence that this medication is more efficacious than the others, at least for first-episode patients," he said.

"Our take-home to clinicians is to avoid higher-risk agents in FES patients, promote a healthy lifestyle, do the monitoring, and integrate physical and mental health care."

Failure to Address Risk

Medscape Medical News invited William T. Carpenter Jr, MD, professor of psychiatry and pharmacology at the University of Maryland School of Medicine, Baltimore, to share his views on the study results.

"The findings are not at all surprising and are an important advance just in documenting how early significant adverse metabolic effects are observed," Dr Carpenter, who was also chair of the DSM-5 Psychotic Disorders work group, said.

Schizophrenia and possibly other psychoses are associated with metabolic risk as an innate component of such illness, which is then complicated by the typical lifestyle behavioral risks and, finally, by exposure to antipsychotic drugs, many of which have very significant adverse metabolic effects, he noted.

"How rapidly some therapeutic medications can increase metabolic risk is very important and suggests that clinicians should consider the metabolic profile of antipsychotic drugs when making an initial selection. Don't wait for weight gain or metabolic parameters to change," Dr Carpenter said.

"This is a major public health challenge, and the widespread failure to detect and address these risk factors is shameful," he added.

"It would be important to know how many of the patients in this study met criteria for statins and failed to have them prescribed, or whether dietary, exercise, smoking cessation, and other prevention measures were recommended or implemented by primary care doctors or initial psychiatric contacts prior to entering the RAISE program.

"The US healthcare system is totally inadequate in caring for the mentally ill, including basic preventive clinical care for those persons with psychosis, despite the high mortality rates and the well-established risk and prevention measures," Dr Carpenter said.

The study was supported in part by the National Institute of Mental Health and by federal funds from the American Recovery and Reinvestment Act. Dr Correll has been a consultant and advisor and has received honoraria from Actelion, Alexa, the American Academy of Child and Adolescent Psychiatry, Bristol-Myers Squib, Cephalon, Eli Lilly and Co, Genentech, Gerson Lehrman Group, IntraCellular Therapies, Lundbeck, Medavante, Medscape, Merck, the National Institute of Mental Health, Janssen/Johnson & Johnson, Otsuka, Pfizer, ProPhase, Roche, Sunovion, Takeda, Teva, and Vanda, and has received grant support from Bristol-Myers Squibb, the Feinstein Institute for Medical Research, Janssen/Johnson & Johnson, the National Institute of Mental Health, the National Alliance for Research in Schizophrenia and Depression, Novo Nordisk A/S, and Otsuka. Dr Carpenter reports no relevant financial relationships.

JAMA Psychiatry. Published online October 8, 2014. Abstract

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