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Schizophrenia, Antipsychotic Use Associated With ECG Changes

July 10, 2019

By Will Boggs MD

NEW YORK—People with schizophrenia have a different pattern of electrocardiogram (ECG) abnormalities than do controls, and those taking antipsychotics have more such abnormalities than do patients not on the drugs, according to a nationally representative study from Denmark.

"The rate of ECG abnormalities was similar between patients with schizophrenia and controls without psychiatric disease, but interestingly, patients with schizophrenia demonstrated more frequently elevated heart rate, prolonged QT interval, and pathological Q waves, as a sign of prior myocardial infarction, on ECGs," Dr. Christoffer Polcwiartek from Aalborg University Hospital, in Aalborg, Denmark, and Duke University Medical Center, in Durham, North Carolina, told Reuters Health by email.

Life expectancy of people with schizophrenia is nearly 20 years shorter than that of the general population, and cardiovascular disease is their leading cause of death.

Dr. Polcwiartek and colleagues used data from linked registries including nearly 1 million digital ECGs to investigate ECG characteristics of 4,486 patients with schizophrenia compared with 22,430 matched controls without prior psychiatric diagnoses or psychotropic drug use.

Almost 75% of patients with schizophrenia received antipsychotics, and more than 30% received antipsychotic polypharmacy, antidepressants, and benzodiazepines, the researchers report in Schizophrenia Bulletin, online June 20.

Just over half of patients with and without schizophrenia had ECG abnormalities.

Compared with controls, patients with schizophrenia had significantly higher median heart rate (79 bpm vs. 69 bpm for controls), longer QTc interval (416 ms vs. 412 ms) and higher prevalence of QTc prolongation (3.4% vs. 1.1%) and pathological Q waves (5.3% vs. 3.9%).

However, significantly fewer patients with schizophrenia than controls met ECG criteria for left ventricular hypertrophy (6.1% vs. 9.6%) and atrial fibrillation or flutter (0.7% vs. 1.4%).

Among patients with schizophrenia, the odds of abnormal ECGs were 20% higher with redeemed prescriptions of antipsychotics, 29% higher with antipsychotic polypharmacy, and 15% higher with benzodiazepines.

With the exception of serotonin and norepinephrine reuptake inhibitors (SNRIs), which were associated with a lower odds of abnormal ECGs, antidepressants, lithium, and other QT-prolonging drugs were not associated with abnormal ECGs.

"Reasons for the excess cardiovascular mortality are multifactorial in this vulnerable patient group," Dr. Polcwiartek said. "Therefore, particularly special attention in the diagnostic work-up of patients with schizophrenia is needed including ECG in case of cardiovascular risk factors or symptoms, revision or addition of psychotropic or cardiovascular drug treatment, attention to psychotropic polypharmacy, and consideration of secondary care referral for further examination, thereby coming to a more integrated psychiatry and cardiovascular care."

Dr. Alessandro Serretti of the University of Bologna, in Italy, who has researched genetic contributions to QTc prolongation associated with psychopharmacological treatments, told Reuters Health by email, "I would interpret the finding in the opposite direction: ECG alterations are quite uncommon in subjects with schizophrenia. In fact, despite QTc prolongation and other abnormalities being significantly higher in schizophrenia subjects, still the difference in percent is very low compared to controls. And, as the authors discuss, it may be due to lifestyle, treatment, and psychopathology issues, so I would have expected even more difference."

"This is another demonstration that the QTc increased risk of many medications for schizophrenia is much overvalued," he said.

The study did not have commercial funding. Dr. Polcwiartek and several coauthors reported ties to antipsychotic makers.


Schizophr Bull 2019.

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