Contents

Search

antipsychotic agent

Classification: 1) traditional a) high potency dopamine D2 receptor antagonist b) low potency dopamine D2 receptor antagonist 2) atypical Indications: - approved indications - schizophrenia - schizo-affective disorder - schizophreniform disorder - delusional disorders [29] - mood disorders - bipolar disorder, mania [7] - severe depressiom refractory to other treatment &/or with psychosis) - psychosis in the absence of dementia - medical illness with psychotic symptoms - neoplasm, acute psychosis, delirium, acute intermittent porphyria - treatment-related psychosis or mania (high-dose glucocooorticoids) - behavioral or psychological symptoms of dementia - Gilles-de-la-Tourette's syndrome or Huntington disease - hiccups not induced by other medications - nausea/vomiting induced by cancer or chemotherapy - off-label uses - psychosis & agitation in the elderly after failure of conservative measures - challenging behaviors in adults with intellectual disability after failure of conservative measures [18] - suicidal ideation [7] - episodic dyscontrol syndrome - apprehension, anxiety - tetanus - alcoholism - autism - criteria for behavioral symptoms - behavioral symptoms present a danger to the resident or others - symptoms identified as due to psycosis or mania - auditory hallucinations, visual hallucinations, other hallucinations, delusions, paranoia or grandiosity - behavioral interventions have been attempted & included in the plan of care, except in a emergency - persistence of symptoms * most antipsychotics in the U.K prescribed at lower doses for anxiety, dementia, & sleep disorders Contraindications: - lack of appropriate evaluation & continual monitoring - 2 or more antipsychotics concurrently - 1st-line treatment for psychosis & agitation in the elderly - 1st-line treatment for management of challenging behaviors in adults with intellectual disability [18] - 1st-line therapy for insomnia - 1st-line treatment for pediatric patients for any condition other than a psychotic disorder [6] - behavior due to medical condition - behavior due to environmental stressors - behavior due to psychological stressors Pregnancy catergory: - risk of extrapyramidal signs in infants born to mothers taking antipsychotics in the 3rd trimester of pregnancy [16] - associated with minimal risk during pregnancy [17] Benefit/risk: - treatment of agitation demented patients - increased risk for mortality (NNH = number needed to harm) - haloperidol NNH = 26 - risperidone, NNH = 27 - olanzapine, NNH = 40 - quetiapine, NNH = 50 Dosage: - when antipsychotic therapy is initiated, informed consent must be documented [29] - when antipsychotic therapy is increased, informed consent must be documented [29] - when antipsychotic therapy is decreased or discontinued, informed consent is not needed - emergency therapy to limited to 7 days, with re-evaluation in 7 days* * non-pharmaceutical measures must be attempted Pharmacokinetics: 1) variable absorption 2) highly bound to plasma proteins 3) widely distributed to tissues including CNS 4) metabolized by liver 5) 1/2 of the dose excreted by liver, the other 1/2 through the enterohepatic circulation 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 f) akathisia [3] g) gait disturbance [3] 4) 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 [9] d) caution is needed for people with more severe neuropsychiatric symptoms [9] 5) increased risk of mortality in patients with dementia (RR=1.35) [29] 6) increased risk of mortality in Parkinson's disease (RR=2.35) [21] 6) typical antipsychotics as a class are associated with 7) an increased risk of out-of-hospital cardiac arrest (RR=1.66) [13] - atypical antipsychotics are not (except quetiapine) 8) increased risk of pneumonia in elderly; (RR=1.6-2.0) [24,30] - increased risk of aspiration pneumonia in patients hospitalized for non-psychiatric conditions (RR=1.5) [25] 9) acute kidney injury: RR=1.6-1.7 [30] 10) venous thromboembolism (VTE): RR=1.5-1.6 [30] 11) stroke: RR=1.5-1.6 [30] 12) fracture: RR=1.43 [30] 13) myocardial infarction: RR=1.28 [30] 14) heart failure: RR=1.27 [30] 15) antipsychotic use during 1st trimester of pregnancy not associated with increased risk of congenital malformation [22] - risperidone may carry small risk [22] 16) black box warning - increased risk of stroke - increased mortality in patients with dementia [26,29] Mechanism of action: - antipsychotics block dopamine & decrease inhibition of prolactin release from the pituitary [27] Notes: - atypical antipsychotics may not be more effective than older agents in the treatment of schizophrenia - all agents are discontinued more frequently than not [4] - over-prescribed in nursing home setting [5] - variation in prescribing patterns in nursing homes [10] - attempt to reduce antipsychotic use should be accompanied by non-pharmacologic measures (i.e. increased social interactions) otherwise neuropsychiatric deterioration may occur [19]

Interactions

drug interactions drug adverse effects (more general classes)

Related

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

Specific

acamprosate (Campral, Alcomed) acetophenazine (Tindal, Phentoxate, Tindala) atypical antipsychotic agent; second generation antipsychotic benperidol; Anquil; Frenactyl; Glianimon chlorpromazine (Thorazine, Ormazine, Propaphenin, Sonazine, Chloractil) chlorprothixene (Taractan, Tarasan, Minithixen, Truxal) clozapine (Clozaril) deserpidine fluphenazine (Prolixin, Anatensol, Triflumethazine, Calmansial, Modecate) haloperidol (Haldol, Halperon, Aloperidol, Halomonth) loxapine (Loxitane, Dibenzoazepine, Cloxazepin) lumateperone (Caplyta) melperone (Buronil) mesoridazine (Serentil, Calodal) molindone (Moban, Lindone) perazine; pernazine; Taxilan; Psytomin perphenazine (Trilafon) pimavanserin (Nuplazid) pimozide (Orap) promazine (Sparine) thioridazine (Mellaril, Millazine, Melleretten) thiothixene (Navane, Tiotixene) trifluoperazine (Stelazine, Suprazine) triflupromazine (Vesprin, Flumazin) tropsium chloride/xanomeline (Cobenfy, KarXT)

General

psychotropic agent

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1147
  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
  4. 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 - Prescriber's Letter 12(9): 2005 Role of atypical antipsychotics in treating patients with Schizophrenia: Are they better than older agents? Detail-Document#: 211107 (subscription needed) http://www.prescribersletter.com
  5. Briesacher BA et al. Antipsychotic use among nursing home residents. JAMA 2013 Feb 6; 309:440. PMID: 23385262
  6. Choosing Wisely. American Psychiatric Association Five Things Physicians and Patients Should Question. http://www.choosingwisely.org/doctor-patient-lists/american-psychiatric-association/
  7. Deprecated Reference
  8. Prescriber's Letter 15(12): 2008 Common Oral Medications that May Need Tapering Detail-Document#: 241208 (subscription needed) http://www.prescribersletter.com
  9. 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
  10. Chen Y, Briesacher BA, Field TS, Tjia J, Lau DT, Gurwitz JH. Unexplained variation across US nursing homes in antipsychotic prescribing rates. Arch Intern Med. 2010 Jan 11;170(1):89-95 PMID: 20065204
  11. Kamble P, Chen H, Sherer JT, Aparasu RR. Use of antipsychotics among elderly nursing home residents with dementia in the US: an analysis of National Survey Data. Drugs Aging. 2009;26(6):483-92. PMID: 19591523
  12. Lester P, Kohen I, Stefanacci RG, Feuerman M. Antipsychotic drug use since the FDA black box warning: survey of nursing home policies. J Am Med Dir Assoc. 2011 Oct;12(8):573-7. PMID: 21450177
  13. Weeke P et al. Antipsychotics and associated risk of out-of-hospital cardiac arrest. Clin Pharmacol Ther 2014 Jun 24 PMID: 24960522
  14. Marston L et al. Prescribing of antipsychotics in UK primary care: A cohort study. BMJ Open 2014 Dec 18; 4:e006135 PMID: 25524544 http://bmjopen.bmj.com/content/4/12/e006135
  15. 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
  16. 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
  17. 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
  18. Sheehan R et al Mental illness, challenging behaviour, and psychotropic drug prescribing in people with intellectual disability: UK population based cohort study. BMJ 2015;351:h4326 PMID: 26330451 http://www.bmj.com/content/351/bmj.h4326
  19. Ballard C et al. Impact of antipsychotic review and nonpharmacological intervention on antipsychotic use, neuropsychiatric symptoms, and mortality in people with dementia living in nursing homes: A factorial cluster-randomized controlled trial by the Well-Being and Health for People with Dementia (WHELD) program. Am J Psychiatry 2015 Nov 20; PMID: 26585409
  20. Herzig SJ, Rothberg MB, Guess JR et al Antipsychotic Use in Hospitalized Adults: Rates, Indications, and Predictors. J Am Geriatr Soc. 2016 Feb;64(2):299-305. PMID: 26889839
  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. Agency for Healthcare Research and Quality (AHRQ) First- and Second-Generation Antipsychotics in Children and Young Adults: Systematic Review Update. Executive Summary - March 16, 2017 https://www.effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=2446
  24. 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 PMID: 20368647 http://www.annals.org/content/152/7/418.abstract
  25. 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
  26. 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: 17548409
  27. Medical Knowledge Self Assessment Program (MKSAP) 17, 18 American College of Physicians, Philadelphia 2015, 2018
  28. Agular JP et al Identification of a Set of Patient-Related Features to Foster Safe Prescribing of Specific Antipsychotics in the Elderly With Dementia. Front Psychiatry, 30 October 2020 Not indexed in PubMed https://www.frontiersin.org/articles/10.3389/fpsyt.2020.604201/full
  29. Asimopoulos M Antipsychotics Associated With Increased Mortality in Patients With Dementia. Annals of Long-Term Care. Jan 20, 2022 https://www.hmpgloballearningnetwork.com/site/altc/news/antipsychotics-associated-increased-mortality-patients-dementia - Norgaard A, Jensen-Dahm C, Wimberley T et al Effect of antipsychotics on mortality risk in patients with dementia with and without comorbidities. J Am Ger Soc 2022. Jan 14 PMID: 35029305
  30. 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
  31. CDPH L&S SNF Antipsychotic Use Survery Tool https://cdn.ymaws.com/www.ascp.com/resource/collection/0BC2F6FB-85B6-49BA-B1E7-5F11C4E319B9/ASCP-CA-CDPHAntipsychoticSurveyToolRevised2014.pdf