Drug Adverse Effects Antipsychotic Agent

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Adverse-effects

• high potency dopamine D2 receptor antagonists

• extrapyramidal symptoms
• neuroleptic malignant syndrome
• hyperprolactinemia

• low potency dopamine D2 receptor antagonists

• anticholinergic effects
• postural ( orthostatic) hypotension

• related to alpha-adrenergic receptor antagonism

• sedation

• 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]

• 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]

• 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

• * RR in demented patients

• 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

• increased risk of pneumonia in elderly; 1.8-1.6 fold [11]
• increased risk of venous thromboembolism (absolute risk low) [12]
• risk of extrapyramidal signs in infants born to mothers taking antipsychotics in th 3rd trimeste of pregancy [13]

More General Terms

• drug adverse effect(s)

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. Haddad PM, Anderson IM. Antipsychotic-related QTc prolongation, torsade de pointes and sudden death. Drugs. 2002;62(11):1649-71. Review. PMID: [1]
5. Daubert GP, Emergency Medicine, University of California, Davis
6. FDA MedWatch [2]
7. Douglas IJ and Smeeth L. Exposure to antipsychotics and risk of stroke: Self controlled case series study. BMJ 2008 Aug 28; 337:a1227. PMID: [3]
8. Prescriber's Letter 15(12): 2008 Common Oral Medications that May Need Tapering Detail-Document#: [4] (subscription needed) [5]
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. <PubMed> PMID: [6] <Internet> [7]
10. Ray WA et al, Atypical antipsychotic drugs and the risk of sudden cardiac death. NEJM 2009, 360:225 PMID: [8]
11. 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: [9] <Internet> [10]
12. Parker C et al Antipsychotic drugs and risk of venous thromboembolism: nested case-control study BMJ 2010; 341:c4245 <PubMed> PMID: [11] <Internet> [12]
    - Liperoti R and Gambassi G Antipsychotics and the risk of venous thromboembolism. BMJ 2010; 341:c4216 <PubMed> PMID: [13] <Internet> [14]
13. FDA MedWatch Feb 22, 2011 Antipsychotic drugs: Class Labeling Change - Treatment During Pregnancy and Potential Risk to Newborns [15]
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 <PubMed> PMID: [16] <Internet> [17]
    - McCleery J and Fox R Antipsychotic prescribing in nursing homes BMJ 2012;344:e1093 <PubMed> PMID: [18] <Internet> [19]
15. Kales HC et al. Risk of mortality among individual antipsychotics in patients with dementia. Am J Psychiatry 2012 Jan; 169:71 PMID: [20]
16. Pariente A et al. Antipsychotic use and myocardial infarction in older patients with treated dementia. Arch Intern Med 2012 Apr 23; 172:648 PMID: [21]

drug adverse effects of antipsychotic agents