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citalopram (Celexa, nitalapram)

Citalopram HBr. Tradename: Celexa. C20H22BrFN2O Indications: 1) depression* a) favorable effect on agitation in demented patients b) may improve cognitive function in demented patients with depression c) bipolar disorder, mania 2) obsessive-compulsive disorder (OCD) 3) post-traumatic stress disorder (PTSD) [16] 4) panic disorder 5) generalized anxiety disorder 6) hot flashes associated with menopause [16] 7) self-injurious behavior 8) psychosis & agitation in the elderly [22] - citalopram benefits some patients, harms others, but most are unaffected * on list of drugs to avoid for treatment of depression [24] - risk of QT prolongation cited Contraindications: 1) concurrent administration of monamine oxidase (MAO) inhibitors 2) concurrent administration of pimozide 3) unfavorable risk profile in children & adolescents [7] 4) NO benefit for coronary artery disease (non-indication) [7] 5) congenital long QT syndrome [14] 6) bradycardia 7) hypokalemia 8) hypomagnesemia 9) recent myocardial infarction 10) uncompensated heart failure [14] Dosage: 1) 20-40 mg PO QD; max dose 40 mg [10,14]* 2) elderly: start 10 mg PO QD; max 20 mg/day [11,14] 3) optimal dosage for major depression is 33.3 mg QD [21] Tabs: 10, 20, 40 mg * dose reductions from average dose of 64 mg/day to <= 40 mg/day among veterans resulted in greater risk for all-cause death or hospitalizations (RR=4.5) & for principal depression diagnosis with death or depression-related hospitalization (RR=2.2) [23] * principal arrhythmia diagnoses were not different at doses of citalopram > or < 40 mg/day [23] Pharmacokinetics: 1) rapid, near complete absorption of oral dose, not affected by food; bioavailability is 80% 2) peak plasma levels reached in 4 hours after oral dose 3) plasma protein binding is 80% 4) metabolized in the liver by cyt P450 (CYP2C19 & CYP3A4) [2] 5) elimination 1/2life is 35 hours (1/3 longer in elderly) Adverse effects: 1) cardiovascular a) tachycardia; - may reduce heart rate in some patients - prolongation of the QT interval at doses > 40 mg/day [14] - Torsades de Pointes [10,13] - no increase in mortality at doses > 40 mg/day [15] b) postural hypotension 2) neurologic a) paresthesia b) migraine 3) gastrointestinal a) flatulence b) increased salivation c) nausea/vomiting (common, generally resolves within 1 week) d) anorexia [17] e) diarrhea [17] f) abdominal cramping 4) psychiatric a) impaired concentration b) amnesia c) apathy d) depression e) increased appetite f) confusion g) may accelerate cognitive decline in patients with cognitive impairment [17] 5) dermatologic a) rash b) pruritus 6) endocrine a) amenorrhea/dysmenorrhea b) decreased libido c) hyponatremia (SIADH) [6] 7) polyuria 8) cough 9) abnormal accommodation 10) taste disturbance 11) weight gain & weight loss 12) increased risk of falls [17] 12) possible association with congenital maliformations - may increase risk of septal heart defects when used early in pregnancy [9] - probably not [20] - marginal link with neural tube defects [20] Drug interactions: 1) minimal 2) drugs that inhibit cyt P450 (CYP2C19 or CYP3A4) may increase levels of citalopram & the risk of QT prolongation - CYP2C19 inhibitors: cimetidine, omperazole & to a lesser extent ethinyl estradiol [12] - do not exceed 20 mg citalopram/day when used in combination with CYP2C19 inhibitor [14] 3) any drug that induces cyt P450 (CYP2C19 or CYP3A4) may diminish levels of citalopram 4) inhibition of cyt P450 2D6 (CYP2D6) is NOT significant Laboratory: - citalopram in specimen - citalopram in dried blood spot - citalopram in gastric fluid - citalopram in serum/plasma - citalopram in urine Mechanism of action: 1) most selective of the SSRIs 2) no tolerance to inhibition of serotonin reuptake (rats) 3) racemic mixture, S-enantiomer is active form [1] 4) reduces Abeta production in CSF in humans [19]

Interactions

drug interactions drug adverse effects (more general classes)

Related

cytochrome P450 2C19 (cytochrome P450 2C17, cytochrome P450 11A, mephenytoin 4-hydroxylase, cytochrome P450 254C, CYP2C19) cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

Specific

escitalopram (Lexapro)

General

selective serotonin reuptake inhibitor (SSRI)

Properties

SIZE: MW = 405.4 G/M MISC-INFO: elimination route LIVER protein-binding 80% 1/2life 35 HOURS

Database Correlations

PUBCHEM correlations

References

  1. Forest Pharmaceuticals
  2. Prescriber's Letter 8(3):16-17 2001
  3. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  4. Department of Veterans Affairs, VA National Formulary
  5. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  6. Prescriber's Letter 9(7):38 2002
  7. Journal Watch 24(11):85, 2004 Whittington CJ, Kendall T, Fonagy P, Cottrell D, Cotgrove A, Boddington E. Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet. 2004 Apr 24;363(9418):1341-5. Review. PMID: 15110490 - Jureidini JN, Doecke CJ, Mansfield PR, Haby MM, Menkes DB, Tonkin AL. Efficacy and safety of antidepressants for children and adolescents. BMJ. 2004 Apr 10;328(7444):879-83. Review. No abstract available. Erratum in: BMJ. 2004 May 15;328(7449):1170. PMID: 15073072 http://bmj.bmjjournals.com/cgi/content/full/328/7444/879
  8. Lespoerance F et al, Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial. JAMA 2007, 297:367 PMID: 17244833 - Glassman AH and Bigger JT Antidepressants in coronary artery disease: SSRI reduce depression, but do they save lives? JAMA 2007, 297:411 PMID: 17244839
  9. Pedersen LH et al Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study BMJ 2009;339:b3569 PMID: 19776103 http://www.bmj.com/cgi/content/full/339/sep23_1/b3569 - Chambers C Selective serotonin reuptake inhibitors and congenital malformations BMJ 2009;339:b3525 PMID: 19776102 http://www.bmj.com/cgi/content/extract/339/sep23_1/b3525
  10. FDA MedWatch - 08/24/2011 Celexa (citalopram hydrobromide): Drug Safety Communication - Abnormal Heart Rhythms Associated With High Doses http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm269481.htm
  11. Prescriber's Letter 18(10): 2011 Celexa (Citalopram) and QT Interval Prolongation Detail-Document#: 271002 (subscription needed) http://www.prescribersletter.com
  12. Prescriber's Letter 19(1): 2012 Drug Interactions With Citalopram (Celexa) Detail-Document#: 280107 (subscription needed) http://www.prescribersletter.com
  13. FDA MedWatch: March 28, 2012 Celexa (citalopram hydrobromide) - Drug Safety Communication: Revised Recommendations, Potential Risk of Abnormal Heart Rhythms http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm297624.htm
  14. Castro VM et al QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ 2013;346:f288 PMID: 23360890 http://www.bmj.com/content/346/bmj.f288
  15. Zivin K et al. Evaluation of the FDA warning against prescribing citalopram at doses exceeding 40 mg. Am J Psychiatry 2013 May 3; PMID: 23640689 http://ajp.psychiatryonline.org/article.aspx?articleid=1685280
  16. Deprecated Reference
  17. Porsteinsson AP, Drye LT, Pollock BG et al Effect of Citalopram on Agitation in Alzheimer Disease. The CitAD Randomized Clinical Trial. JAMA. 2014;311(7):682-691 PMID: 24549548 https://jama.jamanetwork.com/article.aspx?articleid=1829989 - Small GW Treating Dementia and Agitation. JAMA. 2014;311(7):677-678 PMID: 24549545 http://jama.jamanetwork.com/article.aspx?articleid=1829969
  18. Trivedi MH, Rush AJ, Wisniewski SR et al Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006 Jan;163(1):28-40. PMID: 16390886
  19. Yager J Might SSRIs Reduce the Risk for Alzheimer Disease? NEJM Journal Watch. May 27, 2014 Massachusetts Medical Society (subscription needed) http://www.jwatch.org - Sheline YI et al. An antidepressant decreases CSF Abeta production in healthy individuals and in transgenic AD mice. Sci Transl Med 2014 May; 6:236re4 PMID: 24828079 http://stm.sciencemag.org/content/6/236/236re4?ijkey=4d44f88a853621ff2f0f2212954925a3b3d7adf8&keytype2=tf_ipsecsha
  20. Reefhuis J et al Specific SSRIs and birth defects: bayesian analysis to interpret new data in the context of previous reports. BMJ 2015;351:h3190 PMID: 26156519 http://www.bmj.com/content/351/bmj.h3190
  21. Jakubovski E et al. Systematic review and meta-analysis: Dose-response relationship of selective serotonin reuptake inhibitors in major depressive disorder. Am J Psychiatry 2015 Nov 10; PMID: 26552940 http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.15030331
  22. Schneider LS et al. Heterogeneity of treatment response to citalopram for patients with Alzheimer's disease with aggression or agitation: The CitAD randomized clinical trial. Am J Psychiatry 2016 Jan 15 PMID: 26771737 http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.15050648
  23. Rector TS et al. Outcomes of citalopram dosage risk mitigation in a veteran population. Am J Psychiatry 2016 May 10 PMID: 27166093
  24. Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/