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drug adverse effects of atypical antipsychotic agents

Adverse effects: 1) hyperglycemia; increased risk of diabetes [2] (may be all atypical antipsychotics) [2] Hazard ratios for development of diabetes mellitus: [3] clozapine 1.57 quetiapine 1.20 olanzapine 1.15 respiridone 1.01 * RR in demented patients - increased risk of diabetic ketoacidosis [20] 2) use of antipsychotics (all types) associated with increased mortality in the elderly [4,5,7,13] a) risk of mortality may be least with risperidone [5]; b) least with quetiapine [14]; however, quetiapine has not been shown effective in treating neuropsychiatric symptoms in dementia [14] c) HR=1.5, number needed to harm = 83 [13] d) mechanism of increased mortality unknown [13] e) see atypical antipsychotic for number needed to harm 3) increased risk of mortality in Parkinson's disease (RR=2.35) [19] 4) short term use of atypical antipsychotics associated with 3-5 fold risk of adverse event leading to hospitalization or death [7,8] 5) increased risk of stroke in patients receiving any antipsychotic [6] a) RR 23% higher in demented vs non demented patients a) RR* = 2.3 atypical antipsychotics b) RR* = 1.7 conventional antipsychotics 6) ventricular arrhythmias - 2-fold increase of sudden cardiac death [10] 7) weight gain, substantial [11] a) olanzapine > quetiapine > risperidone > aripiprazole b) 4.4-8.5 kg after 11 weeks of therapy c) melatonin 5 mg QD may attenuate weight gain [15] 8) extrapyramidal symptoms - see tardive dyskinesia for management of extrapyramidal symptoms - risk of extrapyramidal signs in infants born to mothers taking antipsychotics in the 3rd trimester of pregnancy [12] 9) urinary symptoms 10) akathisia 11) worsening of cognitive impairment [16] 12) acute renal failure in the 1st few months of use in the elderly (1%, RR=1.6) [17] 13) hypotension [17] 14) increased risk of falls & fractures in the elderly, especially in the 1st 90 days [18]

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DRUGS: atypical antipsychotic agent FORM: drug adverse effects atypical antipsychotic agent

References

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  2. Prescriber's Letter 10(11):62 2003
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  10. Ray WA et al, Atypical antipsychotic drugs and the risk of sudden cardiac death. NEJM 2009, 360:225 PMID: 19144938
  11. Correll CU et al Cardiometabolic Risk of Second-Generation Antipsychotic Medications During First-Time Use in Children and Adolescents JAMA. 2009;302(16):1765-1773 PMID: 19861668 http://jama.ama-assn.org/cgi/content/short/302/16/1765 - Varley CK & McClellan J Implications of Marked Weight Gain Associated With Atypical Antipsychotic Medications in Children and Adolescents JAMA. 2009;302(16):1811-1812 PMID: 19861677 http://jama.ama-assn.org/cgi/content/short/302/16/1811
  12. FDA MedWatch Feb 22, 2011 Antipsychotic drugs: Class Labeling Change - Treatment During Pregnancy and Potential Risk to Newborns http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm244175.htm
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  14. Huybrechts KF et al Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study BMJ 2012;344:e977 PMID: 22362541 http://www.bmj.com/content/344/bmj.e977 - McCleery J and Fox R Antipsychotic prescribing in nursing homes BMJ 2012;344:e1093 PMID: 22362540 http://www.bmj.com/content/344/bmj.e1093
  15. Romo-Nava F et al. Melatonin attenuates antipsychotic metabolic effects: An eight-week randomized, double-blind, parallel-group, placebo- controlled trial. Bipolar Disord 2014 Mar 17 PMID: 24636483 http://onlinelibrary.wiley.com/doi/10.1111/bdi.12196/abstract
  16. Vigen CL, Mack WJ, Keefe RS et al Cognitive effects of atypical antipsychotic medications in patients with Alzheimer's disease: outcomes from CATIE-AD. Am J Psychiatry. 2011 Aug;168(8):831-9 PMID: 21572163
  17. Hwang YJ, Dixon SN, Reiss JP et al Atypical Antipsychotic Drugs and the Risk for Acute Kidney Injury and Other Adverse Outcomes in Older Adults: A Population-Based Cohort Study. Ann Intern Med. 2014;161(4):242-248 PMID: 25133360 http://annals.org/article.aspx?articleid=1897100
  18. Fraser LA et al. Falls and fractures with atypical antipsychotic medication use: A population-based cohort study. JAMA Intern Med 2015 Jan 12 PMID: 25581312 http://archinte.jamanetwork.com/article.aspx?articleid=2089230
  19. Weintraub D et al. Association of antipsychotic use with mortality risk in patients with Parkinson disease. JAMA Neurol 2016 Mar 21 PMID: 26999262
  20. NEJM Knowledge+ Endocrinology