citalopram (Celexa, nitalapram)
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Introduction
Citalopram HBr. Tradename: Celexa. C20H22BrFN2O
Indications
- depression*
- favorable effect on agitation in demented patients
- may improve cognitive function in demented patients with depression
- bipolar disorder, mania
- obsessive-compulsive disorder (OCD)
- post-traumatic stress disorder (PTSD)[16]
- panic disorder
- generalized anxiety disorder
- hot flashes associated with menopause[16]
- self-injurious behavior
- 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
- concurrent administration of monamine oxidase (MAO) inhibitors
- concurrent administration of pimozide
- unfavorable risk profile in children & adolescents[7]
- NO benefit for coronary artery disease (non-indication)[7]
- congenital long QT syndrome[14]
- bradycardia
- hypokalemia
- hypomagnesemia
- recent myocardial infarction
- uncompensated heart failure[14]
Dosage
- 20-40 mg PO QD; max dose 40 mg[10][14]*
- elderly: start 10 mg PO QD; max 20 mg/day[11][14]
- 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
- rapid, near complete absorption of oral dose, not affected by food; bioavailability is 80%
- peak plasma levels reached in 4 hours after oral dose
- plasma protein binding is 80%
- metabolized in the liver by cyt P450 (CYP2C19 & CYP3A4)[2]
- elimination 1/2life is 35 hours (1/3 longer in elderly)
elimination via liver
protein binding = 80 %
1/2life = 35 hours
Adverse effects
- cardiovascular
- tachycardia;
- may reduce heart rate in some patients
- prolongation of the QT interval at doses > 40 mg/day[14]
- no increase in mortality at doses > 40 mg/day[15]
- postural hypotension
- tachycardia;
- neurologic
- gastrointestinal
- flatulence
- increased salivation
- nausea/vomiting (common, generally resolves within 1 week)
- anorexia[17]
- diarrhea[17]
- abdominal cramping
- psychiatric
- impaired concentration
- amnesia
- apathy
- depression
- increased appetite
- confusion
- may accelerate cognitive decline in patients with cognitive impairment[17]
- dermatologic
- endocrine
- amenorrhea/dysmenorrhea
- decreased libido
- hyponatremia (SIADH)[6]
- polyuria
- cough
- abnormal accommodation
- taste disturbance
- weight gain & weight loss
- increased risk of falls[17]
- 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]
- may increase risk of septal heart defects when used early in pregnancy[9]
- drug adverse effects of SSRIs
- drug adverse effects of antidepressants
- drug adverse effects of psychotropic agents
Drug interactions
- minimal
- 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]
- any drug that induces cyt P450 (CYP2C19 or CYP3A4) may diminish levels of citalopram
- inhibition of cyt P450 2D6 (CYP2D6) is NOT significant
- drug interaction(s) of oral anticoagulants with selective serotonin reuptake inhibitor (SSRI)
- drug interaction(s) of antidepressant in combination with GLP1-agonist
- drug interaction(s) of ondanstetron with SSRIs
- drug interaction(s) of dextromethorphan with SSRIs
- drug interaction(s) of trazodone with SSRIs
- drug interaction(s) of tramadol with SSRIs
- drug interaction(s) of triptans with SSRIs
- drug interaction(s) of anti-platelet agents with SSRIs
- drug interaction(s) of methylene blue with SSRIs
- drug interaction(s) of linezolid with SSRIs
- drug interaction(s) of statins with SSRIs
- drug interaction(s) of hypericum perforatum (Sr John's wort) with SSRI
- drug interaction(s) of tamoxifen with SSRI
- drug interaction(s) of benzodiazepines with antidepressants
- drug interaction(s) of antidepressants with benzodiazepines
- drug interaction(s) of NSAIDs with SSRIs
- drug interaction(s) of NSAIDs with antidepressants
- drug interaction(s) of citalopram with pimozide
- drug interaction(s) of antidepressant with opiates
- drug interaction(s) of coxib with SSRI
Laboratory
Mechanism of action
- most selective of the SSRIs
- no tolerance to inhibition of serotonin reuptake (rats)
- racemic mixture, S-enantiomer is active form[1]
- reduces Abeta production in CSF in humans[19]
More general terms
More specific terms
Additional terms
- 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)
References
- ↑ 1.0 1.1 Forest Pharmaceuticals
- ↑ 2.0 2.1 Prescriber's Letter 8(3):16-17 2001
- ↑ UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ Department of Veterans Affairs, VA National Formulary
- ↑ Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
- ↑ 6.0 6.1 Prescriber's Letter 9(7):38 2002
- ↑ 7.0 7.1 7.2 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: https://www.ncbi.nlm.nih.gov/pubmed/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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15073072 <Internet> http://bmj.bmjjournals.com/cgi/content/full/328/7444/879 - ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/17244833
Glassman AH and Bigger JT Antidepressants in coronary artery disease: SSRI reduce depression, but do they save lives? JAMA 2007, 297:411 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17244839 - ↑ 9.0 9.1 Pedersen LH et al Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study BMJ 2009;339:b3569 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19776103 <Internet> http://www.bmj.com/cgi/content/full/339/sep23_1/b3569
Chambers C Selective serotonin reuptake inhibitors and congenital malformations BMJ 2009;339:b3525 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19776102 <Internet> http://www.bmj.com/cgi/content/extract/339/sep23_1/b3525 - ↑ 10.0 10.1 10.2 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
- ↑ 11.0 11.1 Prescriber's Letter 18(10): 2011 Celexa (Citalopram) and QT Interval Prolongation Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=271002&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 12.0 12.1 Prescriber's Letter 19(1): 2012 Drug Interactions With Citalopram (Celexa) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=280107&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 13.0 13.1 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
- ↑ 14.0 14.1 14.2 14.3 14.4 14.5 14.6 Castro VM et al QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ 2013;346:f288 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23360890 <Internet> http://www.bmj.com/content/346/bmj.f288
- ↑ 15.0 15.1 Zivin K et al. Evaluation of the FDA warning against prescribing citalopram at doses exceeding 40 mg. Am J Psychiatry 2013 May 3; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23640689 <Internet> http://ajp.psychiatryonline.org/article.aspx?articleid=1685280
- ↑ 16.0 16.1 16.2 Deprecated Reference
- ↑ 17.0 17.1 17.2 17.3 17.4 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: https://www.ncbi.nlm.nih.gov/pubmed/24549548 https://jama.jamanetwork.com/article.aspx?articleid=1829989
Small GW Treating Dementia and Agitation. JAMA. 2014;311(7):677-678 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24549545 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1829969 - ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/16390886
- ↑ 19.0 19.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24828079 <Internet> http://stm.sciencemag.org/content/6/236/236re4?ijkey=4d44f88a853621ff2f0f2212954925a3b3d7adf8&keytype2=tf_ipsecsha - ↑ 20.0 20.1 20.2 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26156519 <Internet> http://www.bmj.com/content/351/bmj.h3190
- ↑ 21.0 21.1 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; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26552940 <Internet> http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.15030331
- ↑ 22.0 22.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26771737 <Internet> http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.15050648
- ↑ 23.0 23.1 23.2 Rector TS et al. Outcomes of citalopram dosage risk mitigation in a veteran population. Am J Psychiatry 2016 May 10 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27166093
- ↑ 24.0 24.1 Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/