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atypical antipsychotic agent; second generation antipsychotic

Indications: a) treatment of psychosis -> both negative & positive symptoms may respond b) agitation - especially useful in the elderly (antipsychotics of choice) c) aggressive behavior d) autism [12] e) depression, bipolar disorder, mania [12] Benefit/risk: - treatment of agitation demented patients - increased risk for mortality (NNH = number needed to harm) - risperidone, NNH = 27 - olanzapine, NNH = 40 - quetiapine, NNH = 50 [18] Dosage: -> do not abruptly discontinue; taper antipsychotic to be discontinued while titrating new antipsychotic Monitor: 1) weight at baseline, then 1, 2, & 3 months after starting or changing therapy, then every 3 months - melatonin 5 mg QD may attenuate weight gain [14] 2) fasting blood glucose at baseline, 3 months, then annually 3) blood pressure at baseline, 3 months, then annually 4) fasting lipid panel at baseline, 3 months, then every 5 years (if normal) 5) consider trying different antipsychotic if a) serum glucose or lipid profile worsen b) weight gain exceeds 5% Adverse effects: 1) extrapyramidal symptoms - risk of tardive dyskinesia less than that with conventional antipsychotics [13] - see tardive dyskinesia for management of extrapyramidal symptoms 2) urinary symptoms 3) akathisia 4) hyperglycemia; increased risk of diabetes [2] {may be all atypical antipsychotics} [2] 5) dyslipidemia [3] 6) weight gain [3] - melatonin 5 mg QD may attenuate weight gain [14] 7) increased mortality in the elderly [4] - RR = 1.54 - number needed to harm [NNH], 87 [10], 50-100 [20] 8) increased risk of mortality in Parkinson's disease (RR=2.35) [19] 9) increased risk of stroke in patients receiving any antipsychotic [6] a) RR 23% higher in demented vs non demented patients b) RR* = 2.3 atypical antipsychotics c) RR* = 1.7 conventional antipsychotics 10) worsening of cognitive impairment [15] 11) increased risk of falls & fractures in the elderly, especially in the 1st 90 days [17] 12) acute renal failure in the 1st few months of use in the elderly (1%, RR=1.6) [16] 13) hypotension [16] 14) hyperprolactinemia (see antipsychotic) 15) black box warning - increased risk of stroke - increased mortality in patients with dementia * RR in demented patients Notes: - atypical antipsychotics may not be more effective than older agents in the treatment of schizophrenia - all agents are discontinued more frequently than not [5]

Interactions

drug interactions drug adverse effects (more general classes) monitor with atypical antipsychotic agents

Related

atypical vs conventional antipsychotics in the elderly Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE)

Specific

amisulpride (Solian, Deniban, Barhemsys) aripiprazole (Abilify) asenapine (Saphris) brexpiprazole (Rxulti) cariprazine (Vraylar) iloperidone; hoperidone (Fanapt) lurasidone (Latuda) LY2140023 (LY404039) olanzapine (Zyprexa, Zydis, Zyprexa, Relprevv) paliperidone (9-hydroxyrisperidone, Invega, Invega Sustenna) quetiapine (Seroquel) risperidone (Risperdal) sertindole (Serlect) ziprasidone (Zeldox, Geodon) zotepine (Losizopilon, Lodopin, Setous, Zoleptil)

General

antipsychotic agent

References

  1. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  2. Prescriber's Letter 10(11):62 2003
  3. Prescriber's Letter 11(3):13 2004 Detail-Document#: 200306 (subscription needed) http://www.prescribersletter.com
  4. FDA Public Health Advisory Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances http://www.fda.gov/cder/drug/advisory/antipsychotics.htm http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#atypical - Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005 Oct 19;294(15):1934-43. PMID: 16234500
  5. Lieberman JA et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005 Sep 22; 353:1209-23. PMID: 16172203
  6. Douglas IJ and Smeeth L. Exposure to antipsychotics and risk of stroke: Self controlled case series study. BMJ 2008 Aug 28; 337:a1227. PMID: 18755769
  7. Prescriber's Letter 16(10): 2009 Comparison of Atypical Antipsychotics Detail-Document#: 251010 (subscription needed) http://www.prescribersletter.com
  8. Prescriber's Letter 17(1): 2010 Atypical Antipsychotics in Kids Detail-Document#: 260102 (subscription needed) http://www.prescribersletter.com
  9. Prescriber's Letter 17(2): 2010 Comparison of Atypical Antipsychotics Detail-Document#: 260206 (subscription needed) http://www.prescribersletter.com
  10. Maher AR et al. Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults. JAMA 2011 Sep 28; 306:1359 PMID: 21954480
  11. Prescriber's Letter 18(12): 2011 CHART: Off-Label Use of Atypical Antipsychotics in Adults CHART: Comparison of Atypical Antipsychotics Detail-Document#: 271207 (subscription needed) http://www.prescribersletter.com
  12. Deprecated Reference
  13. Jeste DV. Tardive dyskinesia rates with atypical antipsychotics in older adults. J Clin Psychiatry. 2004;65 Suppl 9:21-4. PMID: 15189108
  14. 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
  15. 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
  16. 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
  17. 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
  18. Maust DT, Kim HM, Seyfried LS et al. Antipsychotics, other psychotropics, and the risk of death in patients with dementia: Number needed to harm. JAMA Psychiatry 2015;72(5):438-445. Mar 18; PMID: 25786075
  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. Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
  21. Peuskens J, Pani L, Detraux J, De Hert M. The effects of novel and newly approved antipsychotics on serum prolactin levels: a comprehensive review. CNS Drugs. 2014 May;28(5):421-53. Review. PMID: 24677189 Free PMC Article
  22. Rognoni C, Bertolani A, Jommi C. Second-generation antipsychotic drugs for patients with schizophrenia: systematic literature review and meta-analysis of metabolic and cardiovascular side effects. Clin Drug Investig. 2021;41:303-319. PMID: 33686614