drug adverse effects of antipsychotic agents
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Adverse effects
- high potency dopamine D2 receptor antagonists
- low potency dopamine D2 receptor antagonists
- common side effects
- weight gain
- impotence
- skin manifestations
- pigmentary changes in skin
- photosensitivity
- decreased seizure threshold
- tardive dyskinesia
- long term usage
- generally irreversible
- 10-20% of patients
- akathisia[3]
- gait disturbance[3]
- dystonia - treated with benztropine, diphenhydramine[5]
- ventricular arrhythmias
- prolongation of the QT interval[4]
- 2 fold risk of sudden cardiac death[10]
- increased risk of myocardial infarction[16]
- use of antipsychotics (all types) associated with increased mortality in the elderly[6][9][24]
- 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]
- quetiapine lowest risk (0.9 x respiridone)[14]
- however, quetiapine has not been shown effective in treating neuropsychiatric symptoms in dementia[14]
- see antipsychotic agent for number needed to harm
- haloperidol highest risk (twice respiridone)[14]
- increased risk of mortality in Parkinson's disease (RR=2.35)[21]
- increased risk of stroke in patients receiving any antipsychotic[6]
- RR 23% higher in demented vs non demented patients
- RR* = 2.3 atypical antipsychotics
- RR* = 1.7 conventional antipsychotics
- older age is a risk factor
- risk higher for antipsychotics with affinity for
- 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)
- withdrawal effects with abrupt discontinuation[8]
- sweating, salivation, runny nose, flu-like symptoms, paresthesia, bronchoconstriction, urination, gastrointestinal symptoms, anorexia, vertigo, insomnia, agitation, anxiety, restlessness, movement disorders, psychosis
- taper over 1-2 weeks; 3 weeks for clozapine
- antipsychotics can be withdrawn from many older people with dementia[18]
- caution is needed for people with more severe neuropsychiatric symptoms[18]
- 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]
- acute kidney injury: RR=1.72[25]
- venous thromboembolism (VTE): RR=1.62[12][25]
- stroke: RR=1.61[25]
- fracture: RR=1.43[25]
- myocardial infarction: RR=1.28[25]
- heart failure: RR=1.27[25]
- 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]
More general terms
References
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1147
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 712
- ↑ 3.0 3.1 3.2 Sultzer, D. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 4.0 4.1 Haddad PM, Anderson IM. Antipsychotic-related QTc prolongation, torsade de pointes and sudden death. Drugs. 2002;62(11):1649-71. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12109926
- ↑ 5.0 5.1 Daubert GP, Emergency Medicine, University of California, Davis
- ↑ 6.0 6.1 6.2 FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Antipsychotics
- ↑ Douglas IJ and Smeeth L. Exposure to antipsychotics and risk of stroke: Self controlled case series study. BMJ 2008 Aug 28; 337:a1227. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18755769
- ↑ 8.0 8.1 Prescriber's Letter 15(12): 2008 Common Oral Medications that May Need Tapering Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=241208&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 9.0 9.1 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19138567 <Internet> http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(08)70295-3/fulltext
- ↑ 10.0 10.1 Ray WA et al, Atypical antipsychotic drugs and the risk of sudden cardiac death. NEJM 2009, 360:225 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19144938
- ↑ 11.0 11.1 Trifiro G et al Association of Community-Acquired Pneumonia With Antipsychotic Drug Use in Elderly Patients: A Nested Case-Control Study Ann Intern Med April 6, 2010 152:418 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20368647 <Internet> http://www.annals.org/content/152/7/418.abstract
- ↑ 12.0 12.1 Parker C et al Antipsychotic drugs and risk of venous thromboembolism: nested case-control study BMJ 2010; 341:c4245 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20858909 <Internet> http://www.bmj.com/content/341/bmj.c4245.full
Liperoti R and Gambassi G Antipsychotics and the risk of venous thromboembolism. BMJ 2010; 341:c4216 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20858908 <Internet> http://www.bmj.com/content/341/bmj.c4216.full - ↑ 13.0 13.1 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
- ↑ 14.0 14.1 14.2 14.3 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22362541 <Internet> http://www.bmj.com/content/344/bmj.e977
McCleery J and Fox R Antipsychotic prescribing in nursing homes BMJ 2012;344:e1093 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22362540 <Internet> http://www.bmj.com/content/344/bmj.e1093 - ↑ 15.0 15.1 Kales HC et al. Risk of mortality among individual antipsychotics in patients with dementia. Am J Psychiatry 2012 Jan; 169:71 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22193526
- ↑ 16.0 16.1 Pariente A et al. Antipsychotic use and myocardial infarction in older patients with treated dementia. Arch Intern Med 2012 Apr 23; 172:648 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22450214
- ↑ 17.0 17.1 Wu C-S et al. Association of stroke with the receptor-binding profiles of antipsychotics - a case-crossover study. Biol Psychiatry 2013 Mar 1; 73:414. PMID: https://www.ncbi.nlm.nih.gov/pubmed/2287792
- ↑ 18.0 18.1 18.2 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: https://www.ncbi.nlm.nih.gov/pubmed/23543555
- ↑ 19.0 19.1 Weeke P et al. Antipsychotics and associated risk of out-of-hospital cardiac arrest. Clin Pharmacol Ther 2014 Jun 24 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24960522
- ↑ 20.0 20.1 Vigod SN et al Antipsychotic drug use in pregnancy: high dimensional, propensity matched, population based cohort study. BMJ 2015;350:h2298 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25972273 <Internet> http://www.bmj.com/content/350/bmj.h2298
- ↑ 21.0 21.1 Weintraub D et al. Association of antipsychotic use with mortality risk in patients with Parkinson disease. JAMA Neurol 2016 Mar 21 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26999262
- ↑ 22.0 22.1 22.2 Huybrechts KF et al Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations. JAMA Psychiatry. Published online August 17, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27540849 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27552366 <Internet> http://archpsyc.jamanetwork.com/article.aspx?articleid=2545069 - ↑ 23.0 23.1 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: https://www.ncbi.nlm.nih.gov/pubmed/29095482 https://doi.org/10.1111/jgs.15066
- ↑ 24.0 24.1 Gill SS, Bronskill SE, Normand SL et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med 2007 Jun 5; 146:775 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17548409
- ↑ 25.0 25.1 25.2 25.3 25.4 25.5 25.6 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: https://www.ncbi.nlm.nih.gov/pubmed/38631737 https://www.bmj.com/content/385/bmj-2023-076268