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risperidone (Risperdal)

Tradename: Risperdal. Indications: - psychotic disorders with or without negative symptoms - psychosis & agitation in the elderly [16] - non psychotic symptoms associated with dementia in the elderly - manic symptoms associated with bipolar disorder [12] - depression [15] - autism [15] Contraindications: - not useful for agitation in severely demented patients [13] Dosage: 1) start 1 mg PO BID (lower initial dose in elderly) 2) usual effective dose is 4-6 mg/day 3) doses > 6 mg may not provide additional benefit, but do increase incidence of extrapyramidal symptoms 4) max 16 mg/day 5) injection 25-50 mg every 2 weeks -> continue oral therapy for 3 weeks after 1st injection 6) elderly 0.5-2 mg PO daily Tabs: 0.25, 1, 2, 3, 4 mg. Injection: (Risperdal Consta) 25, 37.5, 50 mg vials [11] Pharmacokinetics: 1) peak plasma levels within 1 hour 2) metabolized by cyt P450 2D6 primarily to 9-hydroxy- risperidone (active metabolite*) 3) 1/2life of the parent compound is 3 hours 4) active metabolite* has a 1/2life of 24 hours 5) 1/2life increases in patients with renal or hepatic impairment 6) protein binding 90% 7) injectable form has delayed onset of action (weeks) [11] Adverse effects: 1) not common (1-10%) - extrapyramidal reactions, headache, sedation, impaired concentration, blurred vision, dry mouth, palpitations, syncope, dizziness, nausea, anorexia, anxiety, hyperprolactinemia, sexual dysfunction, sedation - see tardive dyskinesia for management of extrapyramidal symptoms 2) uncommon (< 1%) - hypotension, bradycardia, seizures 3) other - suppresses cough reflex - QT prolongation - agitation - insomnia - dyspepsia - rhinitis - orthostatic hypotension - weight gain, in adolescents 5.3 kg after 11 weeks of therapy [14] - does NOT appear to cause agranulocytosis - sedation occurs at doses > 20 mg/day - MINIMAL extrapyramidal effects - rigidity is most common - frequency & severity is dose-dependent - anticholinergic effects NOT prominent - also see clozapine - parkinsonism in 20% of nursing home residents [7] - increased risk of falls - stroke, transient ischemic attack (TIA) [8,9] - risk increase (from 2% - 4%) {double} in demented patients prescribed risperidone for agitation [9] - risk NOT observed for other indications [9] - hyperglycemia; increased risk of diabetes mellitus [10] - increased serum triglycerides [14] - may carry small risk of congenital birth defects [17] - does not appear to increase risk of osteoporosis [18] 4) black box warning [16] - increased risk of hyperglycemia - increased risk of cerebrovascular events - increased risk of mortality in patients with dementia - see atypical antipsychotic agent for number needed to harm Drug interactions: 1) inhibitors of cyt P450 2D6 decrease metabolism (activation) of risperidone - cimetidine, haloperidol, perphenazine, propoxyphene, quinidine, ritonavir, paroxetine, sertraline, fluoxetine 2) other agents that prolong the QT interval 3) repsiridone may antagonize effects of L-dopa & dopamine agonists 4) chronic administration of carbamazepine may increase risperidone clearance as much as 50% [12] 5) similar to clozapine Mechanism of action: 1) atypical antipsychotic 2) combined dopamine & serotonin receptor blockade a) potent 5HT-2 receptor antagonist b) dopamine D2 receptor antagonist 3) strong affinity for: a) alpha adrenergic receptors b) histamine H1 receptor c) muscarinic receptors

Interactions

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

Related

clozapine (Clozaril) cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6) QT interval

General

atypical antipsychotic agent; second generation antipsychotic dopaminergic receptor antagonist serotonin antagonist

Properties

MISC-INFO: elimination route LIVER KIDNEY 1/2life 3-24 HOURS protein-binding 90% pregnancy-category C safety in lactation -

Database Correlations

PUBCHEM cid=5073

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 Department of Veterans Affairs, VA National Formulary - restricted to psychiatry
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  6. Journal Watch 22(4):27, 2002 Csernansky et al, N Engl J Med 346:16, 2002
  7. Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004
  8. http://www.fda.gov/medwatch/safety/2003/risperdal.htm
  9. Risperdal and Cerebrovascular Adverse Events in Elderly Patients With Dementia Prescriber's Letter 10(5):29 2003 Detail-Document#: 190507 (subscription needed) http://www.prescribersletter.com - Brodaty H, Ames D, Snowdon J, Woodward M, Kirwan J, Clarnette R, Lee E, Lyons B, Grossman F. A randomized placebo-controlled trial of risperidone for the treatment of aggression, agitation, and psychosis of dementia. J Clin Psychiatry. 2003 Feb;64(2):134-43. PMID: 12633121
  10. Prescriber's Letter 10(11):62 2003
  11. Risperdal Consta (Long-acting Injectable Risperidone) Prescriber's Letter 10(12):70 2003 Detail-Document#: 191212 (subscription needed) http://www.prescribersletter.com
  12. Risperdal (Risperidone) for Bipolar Mania Prescriber's Letter 11(1):4 2004 Detail-Document#: 200109 (subscription needed) http://www.prescribersletter.com
  13. Journal Watch 25(12):96, 2005 Ballard C, Margallo-Lana M, Juszczak E, Douglas S, Swann A, Thomas A, O'Brien J, Everratt A, Sadler S, Maddison C, Lee L, Bannister C, Elvish R, Jacoby R. Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial. BMJ. 2005 Apr 16;330(7496):874. Epub 2005 Feb 18. PMID: 15722369 - Gauthier S Drugs for Alzheimer's disease and related dementias. BMJ. 2005 Apr 16;330(7496):857-8. No abstract available. PMID: 15831849 http://bmj.bmjjournals.com/cgi/content/full/330/7496/874
  14. Correll CU et al Cardiometabolic Risk of Second-Generation Antipsychotic Medications During First-Time Use in Children and Adolescents JAMA. 2009;302(16):1765-1773 PMID: 19861668 http://jama.ama-assn.org/cgi/content/short/302/16/1765 - Varley CK & McClellan J Implications of Marked Weight Gain Associated With Atypical Antipsychotic Medications in Children and Adolescents JAMA. 2009;302(16):1811-1812 PMID: 19861677 http://jama.ama-assn.org/cgi/content/short/302/16/1811
  15. Deprecated Reference
  16. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  17. 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
  18. Clapham E, Boden R, Reutfors J et al. Exposure to risperidone versus other antipsychotics and risk of osteoporosis-related fractures: A population-based study. Acta Psychiatr Scand 2019 Sep 23; PMID: 31545521 https://onlinelibrary.wiley.com/doi/full/10.1111/acps.13101