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Objective <p>Existing evidence suggests a close association between antidepressants (ATDs) and the increased incidence of psychiatric disorders. However, causality has yet to be confirmed. We aim to evaluate the causal relationship between ATDs and five psychiatric disorders using the Two-sample Mendelian Randomization (TSMR) method.</p> Methods <p>This study utilized TSMR analysis to explore the causal impact of ATDs on convulsion (CONV), schizophrenia (SCZ), obsessive-compulsive disorder (OCD), substance abuse (SA), and suicide or self-harm (SOSH). The primary evaluation of causality was conducted using the Inverse Variance Weighted (IVW) method; supplementary validations were performed using the Weighted median, Weighted mode, and MR Egger methods. Sensitivity analyses, including MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis, were conducted to assess potential heterogeneity and pleiotropy.</p> Results <p>The IVW method results revealed a significant positive causal relationship between genetically predicted ATDs and CONV (OR = 1.174; 95% CI 1.038, 1.328; <i>P</i> = 0.011), SCZ (OR = 1.177; 95% CI  1.038, 1.335; <i>P</i> = 0.011), OCD (OR = 1.755; 95% CI 1.355, 2.273; <i>P</i> = 2.06E-05), SA (OR = 1.326; 95% CI  1.222, 1.440; <i>P</i> = 1.61E-11), and SOSH (OR = 1.461; 95% CI 1.394, 1.532; <i>P</i> = 1.71E-50). The supplementary and sensitivity analyses indicated robust and reliable findings.</p> Conclusion <p>Our study suggests that ATDs are potential risk factors for CONV, SCZ, OCD, SA, and SOSH. It is necessary to comprehensively evaluate both the therapeutic effects and potential risks of ATDs in clinical practice. Individualized treatment plans should be formulated for patients with CONV, SCZ, OCD, SA, and SOSH, with increased attention during the clinical use of ATDs.</p>

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Evidence of increased risk of five psychiatric disorders due to antidepressants

  • 期刊论文

  • 发表日期：

    2025年10月30日

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  • Lu Hou,
  • Zhiqiang Du,
  • Rongrong Lu,
  • Ying Jiang,
  • Haohao Zhu

摘要

Objective

Existing evidence suggests a close association between antidepressants (ATDs) and the increased incidence of psychiatric disorders. However, causality has yet to be confirmed. We aim to evaluate the causal relationship between ATDs and five psychiatric disorders using the Two-sample Mendelian Randomization (TSMR) method.

Methods

This study utilized TSMR analysis to explore the causal impact of ATDs on convulsion (CONV), schizophrenia (SCZ), obsessive-compulsive disorder (OCD), substance abuse (SA), and suicide or self-harm (SOSH). The primary evaluation of causality was conducted using the Inverse Variance Weighted (IVW) method; supplementary validations were performed using the Weighted median, Weighted mode, and MR Egger methods. Sensitivity analyses, including MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis, were conducted to assess potential heterogeneity and pleiotropy.

Results

The IVW method results revealed a significant positive causal relationship between genetically predicted ATDs and CONV (OR = 1.174; 95% CI 1.038, 1.328; P = 0.011), SCZ (OR = 1.177; 95% CI  1.038, 1.335; P = 0.011), OCD (OR = 1.755; 95% CI 1.355, 2.273; P = 2.06E-05), SA (OR = 1.326; 95% CI  1.222, 1.440; P = 1.61E-11), and SOSH (OR = 1.461; 95% CI 1.394, 1.532; P = 1.71E-50). The supplementary and sensitivity analyses indicated robust and reliable findings.

Conclusion

Our study suggests that ATDs are potential risk factors for CONV, SCZ, OCD, SA, and SOSH. It is necessary to comprehensively evaluate both the therapeutic effects and potential risks of ATDs in clinical practice. Individualized treatment plans should be formulated for patients with CONV, SCZ, OCD, SA, and SOSH, with increased attention during the clinical use of ATDs.