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Incident diabetes in adolescents using antidepressant: a systematic review and meta-analysis

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Abstract

Background: The use of antidepressants has been on the rise among adolescents and young adults, populations also increasingly at risk for type 2 diabetes. However, the relationship between antidepressant uses and diabetes incidence in these age groups remains poorly understood. Methods: Adhering to PRISMA guidelines and the Cochrane Handbook, we conducted a comprehensive search in PubMed, Scopus, Embase, and Web of Science up to 21 February 2024, registering our protocol on PROSPERO (CRD42024516272). Results: Six studies, ranging from 16, 470 to 1, 582, 914 participants and spanning 2010 to 2023 across North America, Europe, and Asia, were included. The meta-analysis revealed a significant association between antidepressant use and diabetes onset, with 10 cases per 1, 000 observations (p < 0.01; I2 = 100%). Adolescents using high doses of antidepressants showed a 62% increased risk of develo** diabetes compared to non-users or those on low doses (Risk ratio = 1.67; 95% CI 1.19–2.35; I2 = 87%; p < 0.01). The overall quality of the studies was high, with an average Newcastle–Ottawa Scale score of 7.66. Sensitivity analysis highlighted the robustness of these findings, except when removing specific studies, indicating potential sources of heterogeneity. Conclusion: Antidepressant use in adolescents is associated with a significantly increased risk of diabetes onset, particularly at higher doses. This finding underscores the necessity for vigilant monitoring of glucose levels in this population and warrants further investigation into the underlying mechanisms and long-term outcomes.

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Data availability statement

Data is available through contacting the corresponding author with reasonable request.

References

  1. Glowinski AL, D’Amelio G (2016) Depression is a deadly growing threat to our youth: Time to rally. Pediatrics 138(6):e20162869

    Article  PubMed  Google Scholar 

  2. Westberg KH, Nyholm M, Nygren JM, Svedberg P (2022) Mental Health Problems among Young People-A Sco** Review of Help-Seeking. Int J Environ Res Public Health 19(3):1430

    Article  PubMed  PubMed Central  Google Scholar 

  3. Olfson M, Druss BG, Marcus SC (2015) Trends in mental health care among children and adolescents. N Engl J Med 372(21):2029–2038

    Article  PubMed  Google Scholar 

  4. Schüle C (2007) Neuroendocrinological mechanisms of actions of antidepressant drugs. J Neuroendocrinol 19(3):213–226

    Article  PubMed  Google Scholar 

  5. Burcu M, Zito JM, Safer DJ, Magder LS, Shaya FT, Rosenthal GL (2017) Association of antidepressant medications with incident type 2 diabetes among Medicaid-insured youths. JAMA Pediatr 171(12):1200–1207

    Article  PubMed  PubMed Central  Google Scholar 

  6. Sun JW, Hernández-Díaz S, Haneuse S, Bourgeois FT, Vine SM, Olfson M et al (2021) Association of selective serotonin reuptake inhibitors with the risk of type 2 diabetes in children and adolescents. JAMA Psychiat 78(1):91–100

    Article  Google Scholar 

  7. Bhattacharya R, Ajmera M, Bhattacharjee S, Sambamoorthi U (2014) Use of antidepressants and statins and short-term risk of new-onset diabetes among high risk adults. Diabetes Res Clin Pract 105(2):251–260

    Article  CAS  PubMed  Google Scholar 

  8. Siafis S, Papazisis G (2018) Detecting a potential safety signal of antidepressants and type 2 diabetes: a pharmacovigilance-pharmacodynamic study. Br J Clin Pharmacol 84(10):2405–2414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kuo HY, Chen HM, Lee CC, Lee HH, Kuo CJ, Hsu CS et al (2020) Antidepressants and risk of type 2 diabetes mellitus: a population-based nested case-control study. J Clin Psychopharmacol 40(4):359–365

    Article  CAS  PubMed  Google Scholar 

  10. McIntyre RS, Soczynska JK, Konarski JZ, Kennedy SH (2006) The effect of antidepressants on glucose homeostasis and insulin sensitivity: synthesis and mechanisms. Expert Opin Drug Saf 5(1):157–168

    Article  CAS  PubMed  Google Scholar 

  11. Wilkins TL, Sambamoorthi U (2011) Antidepressant use, depression, lifestyle factors, and new-onset diabetes. Int Clin Psychopharmacol 26(3):159–168

    Article  PubMed  Google Scholar 

  12. Strawn JR, Mills JA, Poweleit EA, Ramsey LB, Croarkin PE (2023) Adverse effects of antidepressant medications and their management in children and adolescents. Pharmacotherapy 43(7):675–690

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bhattacharjee S, Bhattacharya R, Kelley GA, Sambamoorthi U (2013) Antidepressant use and new-onset diabetes: a systematic review and meta-analysis. Diabetes Metab Res Rev 29(4):273–284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Salvi V, Grua I, Cerveri G, Mencacci C, Barone-Adesi F (2017) The risk of new-onset diabetes in antidepressant users – A systematic review and meta-analysis. PLoS ONE 12(7):e0182088

    Article  PubMed  PubMed Central  Google Scholar 

  15. Wang Y, Liu D, Li X, Liu Y, Wu Y (2021) Antidepressants use and the risk of type 2 diabetes mellitus: A systematic review and meta-analysis. J Affect Disord 287:41–53

    Article  CAS  PubMed  Google Scholar 

  16. Gafoor R, Booth HP, Gulliford MC (2018) Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up: population based cohort study. BMJ 361:k1951

    Article  PubMed  PubMed Central  Google Scholar 

  17. Himmerich H, Minkwitz J, Kirkby KC (2015) Weight gain and metabolic changes during treatment with antipsychotics and antidepressants. Endocr Metab Immune Disord Drug Targets 15(4):252–260

    Article  CAS  PubMed  Google Scholar 

  18. Laimer M, Kramer-Reinstadler K, Rauchenzauner M, Lechner-Schoner T, Strauss R, Engl J et al (2006) Effect of mirtazapine treatment on body composition and metabolism. J Clin Psychiatry 67(3):421–424

    Article  CAS  PubMed  Google Scholar 

  19. Derijks HJ, Meyboom RH, Heerdink ER, De Koning FH, Janknegt R, Lindquist M, Egberts AC (2008) The association between antidepressant use and disturbances in glucose homeostasis: evidence from spontaneous reports. Eur J Clin Pharmacol 64(5):531–538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chang HH, Chi MH, Lee IH, Tsai HC, Gean PW, Yang YK et al (2013) The change of insulin levels after six weeks antidepressant use in drug-naïve major depressive patients. J Affect Disord 150(2):295–299

    Article  CAS  PubMed  Google Scholar 

  21. Deuschle M (2013) Effects of antidepressants on glucose metabolism and diabetes mellitus type 2 in adults. Curr Opin Psychiatry 26(1):60–65

    Article  PubMed  Google Scholar 

  22. Alruwaili NS, Al-Kuraishy HM, Al-Gareeb AI, Albuhadily AK, Ragab AE, Alenazi AA et al (2023) Antidepressants and type 2 diabetes: highways to knowns and unknowns. Diabetol Metab Syndr 15(1):179

    Article  PubMed  PubMed Central  Google Scholar 

  23. Sartorius N (2018) Depression and diabetes. Dialogues Clin Neurosci 20(1):47–52

    Article  PubMed  PubMed Central  Google Scholar 

  24. Mezuk B, Eaton WW, Albrecht S, Golden SH (2008) Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care 31(12):2383–2390

    Article  PubMed  PubMed Central  Google Scholar 

  25. Golden SH (2007) A review of the evidence for a neuroendocrine link between stress, depression and diabetes mellitus. Curr Diabetes Rev 3(4):252–259

    Article  PubMed  Google Scholar 

  26. Strine TW, Mokdad AH, Dube SR, Balluz LS, Gonzalez O, Berry JT et al (2008) The association of depression and anxiety with obesity and unhealthy behaviors among community-dwelling US adults. Gen Hosp Psychiatry 30(2):127–137

    Article  PubMed  Google Scholar 

  27. Jerrell JM (2010) Neuroendocrine-related adverse events associated with antidepressant treatment in children and adolescents. CNS Neurosci Ther 16(2):83–90

    Article  CAS  PubMed  Google Scholar 

  28. Hsu JW, Chen LC, Huang KL, Tsai SJ, Bai YM, Su TP et al (2023) Risk of type 2 diabetes mellitus between adolescents with antidepressant-resistant and antidepressant-responsive depression: A cohort study of 15, 651 adolescents. J Affect Disord 328:210–214

    Article  CAS  PubMed  Google Scholar 

  29. Burcu M, Zito JM, Safer DJ, Magder LS, dosReis S, Shaya FT, Rosenthal GL (2017) Association of Antidepressant Medications With Incident Type 2 Diabetes Among Medicaid-Insured Youths. JAMA Pediatr 171(12):1200–1207

    Article  PubMed  PubMed Central  Google Scholar 

  30. Andrade SE, Lo JC, Roblin D, Fouayzi H, Connor DF, Penfold RB et al (2011) Antipsychotic medication use among children and risk of diabetes mellitus. Pediatrics 128(6):1135–1141

    Article  PubMed  Google Scholar 

  31. Cao TXD, Filliter C, Montastruc F, Yu OHY, Fergusson E, Rej S et al (2022) Selective serotonin reuptake inhibitors and the risk of type 2 diabetes mellitus in youths. J Affect Disord 318:231–237

    Article  CAS  PubMed  Google Scholar 

  32. Yoon JM, Cho EG, Lee HK, Park SM (2013) Antidepressant use and diabetes mellitus risk: a meta-analysis. Korean J Fam Med 34(4):228–240

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to acknowledge the Clinical Research Development Unit of Imam Ali Hospital, Karaj, and Dr. Mahmood Bakhtiyari for their insightful comments.

Funding

This study did not receive funding, grant, or sponsorship from any individuals or organizations.

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Authors and Affiliations

  1. Tehran University of Medical Sciences, Tehran, Iran

    Fatemeh Movahed & Aida Rezaei Nejad

  2. Student Research Committee, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran

    Ehsan Heidari, Romina Abyaneh, Abolfazl Abdollahi & Arman Shafiee

  3. Student Research Committee, School of Medicine, Isfahan University of Medical Sciences, Qom, Iran

    Dina Sadeghi & Mehrshad Zarei

  4. Student Research Committee, School of Medicine, Arak University of Medical Sciences, Arak, Iran

    Farzan Beigi

Authors
  1. Fatemeh Movahed
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  2. Ehsan Heidari
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  4. Aida Rezaei Nejad
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  9. Arman Shafiee
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Contributions

AS; FM, EH: Conceptualization, Project Administration, Formal analysis, Data curation, Writing- Original Draft, Writing – Review & Editing, Visualization. RA, DM, AR, MZ, AA, FB: Validation, Resources, Writing – Original Draft.

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Correspondence to Arman Shafiee.

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Movahed, F., Heidari, E., Sadeghi, D. et al. Incident diabetes in adolescents using antidepressant: a systematic review and meta-analysis. Eur Child Adolesc Psychiatry (2024). https://doi.org/10.1007/s00787-024-02502-x

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