Antidepressant Plus Antipsychotic Use Linked to Cardiometabolic Complications


Children treated with SSRIs and SGAs concurrently demonstrate higher waist circumference, BMI, and plasma total cholesterol compared to those on monotherapy.


A new study from the American Diabetes Association’s (ADA) 81st Scientific Sessions indicates that simultaneous treatment with selective serotonin reuptake inhibitors (SSRIs) and second-generation antipsychotics (SGAs) for mental health disorders in children may have negative impacts on cardiometabolic health.

The investigators noted that although treatment with either drug has been associated with cardiometabolic complications and increased risk for type 2 diabetes, little is actually known about the concurrent use of both medications.

As such, to evaluate the cardiometabolic impacts of combining treatments, a team, led by Rupinder Thandi, BS, and colleagues at the University of British Columbia, conducted a cross-sectional study of children at their institution’s Department of Children and Adolescent Psychiatry.

The Study

All evaluated patients (n = 569) were 5-18 years of age; presented with a mental health diagnosis; had no endocrine, genetic, or eating disorders; and had not taken any medications affecting their metabolism.

Rupinder and team then sorted patients into 4 cohorts: SSRI and SGA treatment-naïve (n = 242), SSRI only (n = 123), SGA only (n = 112), and SSRI + SGA (n = 92). Patients receiving either or both medications had been administered them for ≥7 days at analysis.

The team collected anthropometric and fasting blood samples from patients and assessed systolic/diastolic blood pressure, glucose homeostasis, and plasma lipids. Adjusted linear and logistic regression models were applied to determine any relationship between treatment groups and cardiometabolic risk factors.

The mean age was 13.04 for the naïve population, 13.61 for the SSRI population, 11.63 for the SGA population, and 12.31 for the SSRI + SGA population.

Further, the most prevalent primary mental health diagnosis across the groups was anxiety disorder. Other primary diagnoses represented in the populations were depressive disorder and ADHD.

The Results

Patients who received SSRI only were administered medication for an average of 5.38 months, and patients who received the combination therapy were administered for an average of 8.00 months.

Overall, the investigators found that SSRI + SGA-treated children had higher waist circumference z-scores (0.91) compared to children treated with SSRI only (0.48; P<0.05)

Additionally, compared to SSRI-treated patients, children in the combined cohort had a greater odds of waist circumference in the ≥90th percentile (odds ratio [OR], 2.63, 95% CI; 1.34-5.18; P<0.05). 

They also had had higher plasma total cholesterol versus SGA only (4.63 vs. 4.34 mmol/L; P<0.05, adjusted by age, sex, and BMI z-scores) and a greater odds of plasma total cholesterol ≥5.18 mmol/L (OR, 2.36; 95% CI. 1.05-5.30; P<0.05).

There were no observed differences in plasma fasting glucose, insulin, or insulin resistance (as measured by homeostasis model assessment of insulin resistance [HOMA-IR]) between the treatment groups.

“Our findings suggest greater cardiometabolic complications in children concurrently treatment with SSRIs and SGAs,” concluded the investigators.

The study, “Impact of Concurrent Use of Selective Serotonin Reuptake Inhibitors and Second-Generation Antipsychotic Medications on Cardiometabolic Health in Children,” was presented at ADA 2021.

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