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drug adverse effects of antipsychotic agents

Adverse effects: 1) high potency dopamine D2 receptor antagonists a) extrapyramidal symptoms b) neuroleptic malignant syndrome c) hyperprolactinemia 2) low potency dopamine D2 receptor antagonists a) anticholinergic effects b) postural (orthostatic) hypotension - related to alpha-adrenergic receptor antagonism c) sedation 3) common side effects a) weight gain b) impotence c) skin manifestations 1] pigmentary changes in skin 2] photosensitivity d) decreased seizure threshold e) tardive dyskinesia - long term usage - generally irreversible - 10-20% of patients - see tardive dyskinesia for management f) akathisia [3] g) gait disturbance [3] h) dystonia - treated with benztropine, diphenhydramine [5] 4) ventricular arrhythmias - prolongation of the QT interval [4] - 2 fold risk of sudden cardiac death [10] - increased risk of myocardial infarction [16] 5) use of antipsychotics (all types) associated with increased mortality in the elderly [6,9,24] a) haloperidol highest risk (twice respiridone) [14] - but patients given haloperidol are more likely to be older, sicker, & black; to have concurrent delirium; to have more inpatient days; & to have taken opioids or benzodiazepines [15] b) quetiapine lowest risk (0.9 x respiridone) [14] c) however, quetiapine has not been shown effective in treating neuropsychiatric symptoms in dementia [14] d) see antipsychotic agent for number needed to harm 6) increased risk of mortality in Parkinson's disease (RR=2.35) [21] 7) 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 d) older age is a risk factor e) risk higher for antipsychotics with affinity for 1] alpha-2 adrenergic receptors 2] muscarinic M1 receptors [17] * RR in demented patients 8) typical antipsychotics as a class are associated with an increased risk of out-of-hospital cardiac arrest (RR=1.66) [19] - atypical antipsychotics are not (except quetiapine) 9) withdrawal effects with abrupt discontinuation [8] a) sweating, salivation, runny nose, flu-like symptoms, paresthesia, bronchoconstriction, urination, gastrointestinal symptoms, anorexia, vertigo, insomnia, agitation, anxiety, restlessness, movement disorders, psychosis b) taper over 1-2 weeks; 3 weeks for clozapine c) antipsychotics can be withdrawn from many older people with dementia [18] d) caution is needed for people with more severe neuropsychiatric symptoms [18] 10) increased risk of pneumonia in elderly; 1.8-1.6 fold [11] - increased risk of aspiration pneumonia in patients hospitalized for non-psychiatric conditions (RR=1.5) [23] 11) acute kidney injury: RR=1.72 [25] 12) venous thromboembolism (VTE): RR=1.62 [12,25] 13) stroke: RR=1.61 [25] 14) fracture: RR=1.43 [25] 15) myocardial infarction: RR=1.28 [25] 16) heart failure: RR=1.27 [25] 17) antipsychotic use during pregnancy - risk of extrapyramidal signs in infants born to mothers taking antipsychotics in the 3rd trimester of pregnancy [13] - associated with minimal risk during pregnancy [20] - antipsychotic use during 1st trimester of pregnancy not associated with increased risk of congenital malformation [22] - risperidone may carry small risk [22]

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DRUGS: antipsychotic agent FORM: drug adverse effects antipsychotic agent

References

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  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 712
  3. Sultzer, D. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
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  5. Daubert GP, Emergency Medicine, University of California, Davis
  6. FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Antipsychotics
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  8. Prescriber's Letter 15(12): 2008 Common Oral Medications that May Need Tapering Detail-Document#: 241208 (subscription needed) http://www.prescribersletter.com
  9. Ballard C et al The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial Lancet Neurol 2009 Feb; 8:151. PMID: 19138567 http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(08)70295-3/fulltext
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  13. 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
  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
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  18. Declercq T, Petrovic M, Azermai M, et al. Withdrawal versus continuation of chronic antipsychotic drugs for behavioural and psychological symptoms in older people with dementia. Cochrane Database Syst Rev. 2013 Mar 28;3:CD007726 PMID: 23543555
  19. Weeke P et al. Antipsychotics and associated risk of out-of-hospital cardiac arrest. Clin Pharmacol Ther 2014 Jun 24 PMID: 24960522
  20. Vigod SN et al Antipsychotic drug use in pregnancy: high dimensional, propensity matched, population based cohort study. BMJ 2015;350:h2298 PMID: 25972273 http://www.bmj.com/content/350/bmj.h2298
  21. Weintraub D et al. Association of antipsychotic use with mortality risk in patients with Parkinson disease. JAMA Neurol 2016 Mar 21 PMID: 26999262
  22. Huybrechts KF et al Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations. JAMA Psychiatry. Published online August 17, 2016 PMID: 27540849 http://archpsyc.jamanetwork.com/article.aspx?articleid=2545072 - Wisner KL et al Use of Antipsychotics During PregnancyPregnant Women Get Sick - Sick Women Get Pregnant. JAMA Psychiatry. Published online August 17, 2016 PMID: 27552366 http://archpsyc.jamanetwork.com/article.aspx?articleid=2545069
  23. Herzig SJ, LaSalvia MT, Naidus E et al. Antipsychotics and the risk of aspiration pneumonia in individuals hospitalized for nonpsychiatric conditions: A cohort study. J Am Geriatr Soc 2017 Dec; 65:2580. PMID: 29095482 https://doi.org/10.1111/jgs.15066
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  25. DePeau-Wilson M Antipsychotics in Dementia Tied to Wider Range of 'Serious Harms' Steepest increases in risk observed for pneumonia, kidney injury, VTE, and stroke. MedPage Today April 17, 2024 https://www.medpagetoday.com/psychiatry/generalpsychiatry/109722 - MOK PLH, Carr MJ, Guthrie B et al Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study. BMJ. 2024 Apr 17;385:e076268 PMID: 38631737 https://www.bmj.com/content/385/bmj-2023-076268 - Kheirbek RE, LaFon C. Use of antipsychotics in adults with dementia: New study identifies a wider range of associated harm. BMJ 2024 Apr 17; 385:q819 PMID: 38631727 https://www.bmj.com/content/385/bmj.q819