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Acta Scientific Pharmaceutical Sciences (ASPS)(ISSN: 2581-5423)

Research Article Volume 4 Issue 10

Off-label Prescription, Adverse Drug Events and Dosage of Psychotropic Drugs in Children and Adolescents with Obesity - A Retrospective Cohort Study

Terese Matthesen Kamronn1,2, Christina Gade3*, Sandra Nielsen3, Hanne Rolighed Christensen3, Kim Peder Dalhoff3, Jens Christian Holm4,5,6 and Helle Holst3,7

1Department of Clinical Pharmacology, Aarhus University Hospital, Denmark
2Department of Clinical Pharmacology, Aalborg University Hospital, Denmark
3Department of Clinical Pharmacology, University Hospital Copenhagen, Bispebjerg and Frederiksberg, Denmark
4Children’s Obesity Clinic, Department of Paediatrics, University Hospital Copenhagen, Holbaek, Denmark
5The Novo Nordisk Foundation Center for Basic Metabolic Research, Copenhagen University, Denmark
6Faculty of Health, Copenhagen University, Denmark
7Lundbeck A/S Department of Clinical Pharmacology, H. Lundbeck A/S, Denmark

*Corresponding Author: Christina Gade, Department of Clinical Pharmacology, University Hospital Copenhagen, Bispebjerg and Frederiksberg, Denmark.

Received: September 01, 2020; Published: September 28, 2020

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Abstract

Background: Children with obesity are more prone to suffer from psychiatric disorders. However, drug dosing in complex, as most psychotropic agents even in low dosage associated with drug-induced weight gain.

Objectives: To describe the extent of off-label use, polypharmacy and potential adverse drug event (ADE) related to psychotropic drugs in children and adolescence with obesity.

Methods: A retrospective cohort study including 1.593 patient records of children admitted to a Children´s Obesity Clinic, receiving at least one psychotropic drug during an eight-year study period. Off label status and potential ADEs were registered by assessing patient records and medical charts.

Results: One hundred-fifty-eight children received at least one psychotropic drug during the study period and 52% received more than one psychotropic drug concurrently. Both antidepressants and antipsychotics were prescribed significantly more to girls > 12 years than boys (p = 0.02). In total, 61% of the children had at least 1 ADE registered, with significantly increased ADEs when treated with more than one psychotropic drug (p < 0.001). Abnormal weight gain was the most frequently ADE in antipsychotics, affecting 35% of the treated patients. Ninety-one percent had at least one off-label prescription, e.g. non-approved indication (31.5%), age (1.9%), dose (23.8%), and duration of treatment (0.6%).

Conclusion: Off-label use and polypharmacy is frequent among children with obesity treated for psychiatric disorders. It is problematic, since most antipsychotic and antidepressant drugs have metabolic adverse effects. These findings highlight the importance of including this patient population in clinical trials to determine appropriate efficacy-safety relationships.

Keywords: Off-label; Adverse Drug Events; Polypharmacy; Obesity; Children and Adolescents

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References

  1. Global Strategy on Diet, Physical Activity and Health | Childhood overweight and obesity. WHO website.
  2. Sjöberg RL., et al. “Obesity, shame, and depression in school-aged children: a population-based study”. Pediatrics 116 (2005): 389-92.
  3. Topçu S., et al. “Anxiety, depression and self-esteem levels in obese children: a case-control study”. Journal of Pediatric Endocrinology and Metabolism 29 (2016): 357-361.
  4. Alonso‐Pedrero L., et al. “Effects of antidepressant and antipsychotic use on weight gain: A systematic review”. Obesity Review 20 (2019): 1680-1690.
  5. Mulder R., et al. “Treating depression with adjunctive antipsychotics”. Bipolar Disorder 20 (2018): 17-24.
  6. Tucker JM., et al. “Psychiatric diagnoses and medication treatment among patients presenting for paediatric weight management: associations with adiposity, aerobic fitness and cardiometabolic health”. Clinical Obesity 7 (2017): 145-150.
  7. Korczak DJ., et al. “Child and Adolescent Psychopathology Predicts Increased Adult Body Mass Index: Results from a Prospective Community Sample”. Journal of Developmental and Behavioral Pediatrics 35 (2014): 108-117.
  8. de Hoogd S., et al. “Differences in Body Mass Index z-Scores and Weight Status in a Dutch Pediatric Psychiatric Population With and Without Use of Second-Generation Antipsychotics”. Journal of Child and Adolescent Psychopharmacology 22 (2012): 166-173.
  9. Bobo WV., et al. “Antipsychotics and the Risk of Type 2 Diabetes Mellitus in Children and Youth”. JAMA Psychiatry 70 (2013): 1067-1075.
  10. Centers for Medicare and Medicaid Services (CMS) Medicaid Integrity Group (MIG). Atypical Antipsychotic Medications: Use in Pediatric Patients (2015).
  11. Nihalani N., et al. “Obesity and psychotropics.” CNS Neuroscience Therapy 18 (2012): 57-63.
  12. Choong E., et al. “Psychotropic drug-induced weight gain and other metabolic complications in a Swiss psychiatric population”. Journal of Psychiatric Research 46 (2012): 540-548.
  13. Correll CU., et al. “Cardiometabolic Risk of Second-Generation Antipsychotic Medications During First-Time Use in Children and Adolescents”. JAMA 302 (2009): 1765-1773.
  14. Sikich L., et al. “Double-Blind Comparison of First- and Second-Generation Antipsychotics in Early-Onset Schizophrenia and Schizo-affective Disorder: Findings from the Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) Study”. American Journal of Psychiatry 165 (2008): 1420-1431.
  15. Zhang J-P., et al. “Pharmacogenetic Associations of Antipsychotic Drug-Related Weight Gain: A Systematic Review and Meta-analysis”. Schizophrenia Bulletin 42 (2016): 1418-37.
  16. Gebhardt S., et al. “Antipsychotic-induced body weight gain: predictors and a systematic categorization of the long-term weight course”. Journal of Psychiatric Research 43 (2009): 620-626.
  17. Auby P. “The European Union Pediatric legislation: impact on pharmaceutical research in pediatric populations”. Clinical Investigation (Lond) 4 (2014): 1013-1039.
  18. Horen B., et al. “Adverse drug reactions and off-label drug use in paediatric outpatients”. British Journal of Clinical Pharmacology 54 (2002): 665-670.
  19. Comer JS., et al. “National trends in child and adolescent psychotropic polypharmacy in office-based practice, 1996-2007”. Journal of the American Academy of Child and Adolescent Psychiatry 49 (2010): 1001-1010.
  20. Braüner JV., et al. “Off-Label Prescription of Psychopharmacological Drugs in Child and Adolescent Psychiatry”. Journal of Clinical Psychopharmacology 36 (2016): 500-507.
  21. Nielsen E., et al. “Off-label prescribing of psychotropic drugs in a Danish child and adolescent psychiatric outpatient clinic”. European Child and Adolescent Psychiatry 25 (2016): 25-31.
  22. Glennon J., et al. “Paediatric European Risperidone Studies (PERS): context, rationale, objectives, strategy, and challenges”. European Child and Adolescent Psychiatry 23 (2014): 1149-1160.
  23. Cella M., et al. “What is the right dose for children?” British Journal of Clinical Psychopharmacology 70 (2010): 597-603.
  24. Mulla H and Johnson TN. “Dosing dilemmas in obese children”. Archives of Disease in Childhood: Education and Practice Edition 95 (2010): 112-117.
  25. Nysom K., et al. “Body mass index of 0 to 45-y-old Danes: reference values and comparison with published European reference values”. International Journal of Obesity and Related Metabolic Disorders 25 (2001): 177-184.
  26. ICD-10 Version: (2016).
  27. WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD Index (2018).
  28. Medical Dictionary for Regulatory Activities. MedDRA.
  29. ICH harmonised tripartite guideline. Clinical Investigation of Medicinal Products in the Pediatric Population (2000).
  30. Version 3.6. Python Software Foundation.
  31. Correll CU., et al. “Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder”. World Psychiatry 14 (2015): 119-136.
  32. Hirsch L., et al. “Second-generation antipsychotics and metabolic side-effects: Canadian population-based study”. BJPsych Open 4 (2018): 256-61.
  33. Chen J., et al. “Molecular Mechanisms of Antipsychotic Drug-Induced Diabetes”. Frontier in Neuroscience 11 (2017): 643.
  34. Gade C., et al. “Higher chlorzoxazone clearance in obese children compared with nonobese peers”. British Journal of Clinical Psychopharmacology 84 (2018): 1738-47.
  35. Fraguas D., et al. “Efficacy and safety of second-generation antipsychotics in children and adolescents with psychotic and bipolar spectrum disorders: comprehensive review of prospective head-to-head and placebo-controlled comparisons”. (2011): 621-645.
  36. Jakobsen KD., et al. “Neurological, Metabolic, and Psychiatric Adverse Events in Children and Adolescents Treated With Aripiprazole”. Journal of Clinical Psychopharmacology 36 (2016): 496-499.
  37. Lee SH., et al. “Is increased antidepressant exposure a contributory factor to the obesity pandemic?” Translational Psychiatry 6 (2016): 759.
  38. Harvey BH and Bouwer CD. “Neuropharmacology of paradoxic weight gain with selective serotonin reuptake inhibitors”. Clinical Neuropharmacology 23 (2000): 90-97.
  39. Gafoor R., et al. “Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up: population based cohort study”. BMJ 361 (2018): 1951.
  40. Jerrell JM and McIntyre RS. “Adverse events in children and adolescents treated with antipsychotic medications”. Human Psychopharmacology: Clinical and Experimental 23 (2008): 283-290.
  41. Correll CU., et al. “Does antipsychotic polypharmacy increase the risk for metabolic syndrome?” Schizophrenia Research 89 (2007): 91-100.
  42. Komossa K., et al. “Second-generation antipsychotics for major depressive disorder and dysthymia”. Cochrane Database System Review (2010): CD008121.
  43. Summary of Product Characteristics. The European Medicines Agency. www.produktresume.dk.
  44. Jain R., et al. “Implications of obesity for drug therapy: limitations and challenges”. Clinical Pharmacology and Therapeutics 90 (2011): 77-89.
  45. Brill MJE., et al. “Impact of obesity on drug metabolism and elimination in adults and children”. Clinical Pharmacokinetics 51 (2012): 277-304.
  46. Kendrick JG., et al. “Pharmacokinetics and Drug Dosing in Obese Children”. ournal of Pediatric Pharmacology and Therapeutics JPPT 15 (2010): 94-109.
  47. Harskamp-van Ginkel MW., et al. “Drug Dosing and Pharmacokinetics in Children With Obesity: A Systematic Review”. JAMA Pediatrics 169 (2015): 678-685.
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Citation

Citation: Christina Gade., et al. “Off-label Prescription, Adverse Drug Events and Dosage of Psychotropic Drugs in Children and Adolescents with Obesity - A Retrospective Cohort Study". Acta Scientific Pharmaceutical Sciences 4.10 (2020): 152-164.



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