Cardiometabolic risk after antidepressant and antipsychotic treatment in major depressive disorder: evidence from German health claims data

Introduction

Major depressive disorder (MDD) is a common and disabling mental health condition characterized by persistent depressed mood or anhedonia, along with impaired functioning. Pharmacological treatment is central to MDD management, most commonly with antidepressants such as selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, and tricyclic antidepressants. In treatment‑resistant cases, antipsychotics are frequently prescribed as adjunctive therapy. However, while cardiometabolic effects of antidepressant and antipsychotic use have been described in clinical trials, evidence from real-world routine care, particularly from German claims data, remains comparatively limited.

Aim(s):

Pharmacologic treatments for MDD, including both antidepressants and adjunctive antipsychotics, differ in their cardiometabolic risk profiles. Treatment‑emergent effects such as weight gain, hypertension, and dyslipidaemia may adversely affect long‑term health and treatment adherence. We estimated the incidence and time to event of key cardiometabolic outcomes among MDD adults treated with antidepressants and/or antipsychotics.

Methods

A retrospective cohort study using German claims data from the WIG2 benchmark database identified adults (≥18 years) between January 2015 and December 2022. Eligible patients had a diagnosis of MDD, defined as two separate codes within the study period (ICD-10-GM: F32 and F33), initiated treatment with an antidepressant or antipsychotic (index date), and had at least 12 months of continuous enrolment prior to and 24 months following the index date, except for death within the follow-up period. Patients with any cardiometabolic outcome, schizophrenia, cognitive impairment, psychotic disorders, dementia, or personality disorders during the available backward period were excluded. Incidence rates (IRs) with 95% confidence intervals (CIs) were estimated based on 1000 person‑months at risk, and the median time to event (TTE) with interquartile range (IQR) was reported.

Results

The cohort comprised 37,112 patients with a median age of 38 years (IQR: 28.0 - 48.0); 55.3% were female. Around 189 patients died during the follow-up period. The mean observation time was 351.6 days (SD: 473.2), and the median was 168 days (IQR: 110 – 360). At baseline, a moderate depressive episode was diagnosed in 50% of patients, while 23% had a mild episode. Most patients (97.2%) initiated treatment with antidepressants, 1.5% with antipsychotics, and the remainder received both therapies. Overall, 10.1% (n=3,748) experienced at least one cardiometabolic event (IR = 10.2; 95% CI: 9.7 – 10.6), with a median TTE of 3.9 months (IQR: 1.1 – 12.1). Hypertension (IR = 3.9; 95% CI: 3.6 – 4.1), hyperlipidaemia (IR = 2.8; 95% CI: 2.5 – 3.0), obesity (IR = 2.5; 95% CI: 2.2 – 2.7), and any cardiovascular disease (IR = 2.0; 95% CI: 1.8 – 2.2) were the most frequently observed outcomes, with median TTE of 4.4 months (IQR: 1.1 – 13.6) for hypertension, 5.6 months (IQR: 1.3 – 19.8) for hyperlipidaemia, 5.6 months (IQR: 1.8 – 16.4) for obesity, and 6.9 months (IQR: 2.0 – 19.8) for any cardiovascular disease.

Conclusions

Among patients with MDD, cardiometabolic events were frequent and occurred soon after treatment initiation, highlighting the importance of further evaluating MDD treatments with respect to their cardiometabolic risk profiles and of early monitoring following treatment initiation.

References

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