Stereo-Psychopharmacology: The Case of Citalopram and Escitalopram

Clinical Pharmacology in Drug Development

Volumn 5, Issue 5, 2016, Pages 331-335

  Ng, Isaac ^a   Greenblatt, H Karl ^a   Greenblatt, David J ^a  

^a TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CITALOPRAM; ESCITALOPRAM; SEROTONIN TRANSPORTER;

ANXIETY DISORDER; BINDING AFFINITY; CARDIOVASCULAR RISK; DRUG EFFICACY; DRUG PROTEIN BINDING; EDITORIAL; HUMAN; MAJOR DEPRESSION; MONTGOMERY ASBERG DEPRESSION RATING SCALE; NONHUMAN; PHARMACODYNAMICS; PRIORITY JOURNAL; PSYCHOPHARMACOLOGY; QT PROLONGATION; RANDOMIZED CONTROLLED TRIAL (TOPIC);

EID: 84987846813     PISSN: 2160763X     EISSN: 21607648     Source Type: Journal    
DOI: 10.1002/cpdd.293     Document Type: Editorial

References (59)

1. Agranat I, Caner H, Caldwell J. Putting chirality to work: the strategy of chiral switches. Nat Rev Drug Discov. 2002;1(10):753–768.
2. Miller CP, Ullrich JW. A consideration of the patentability of enantiomers in the pharmaceutical industry in the United States. Chirality. 2008;20(6):762–770
3. Brooks WH, Guida WC, Daniel KG. The significance of chirality in drug design and development. Curr Top Med Chem. 2011;11(7):760–770.
4. Baker GB, Prior TI. Stereochemistry and drug efficacy and development: relevance of chirality to antidepressant and antipsychotic drugs. Ann Med. 2002;34(7-8):537–543.
5. Hutt AJ. Chirality and pharmacokinetics: an area of neglected dimensionality? Drug Metabol Drug Interact. 2007;22(2-3):79–112.
6. Lu H. Stereoselectivity in drug metabolism. Expert Opin Drug Metab Toxicol. 2007;3(2):149–158.
7. Mansfield P, Henry D, Tonkin A. Single-enantiomer drugs: elegant science, disappointing effects. Clin Pharmacokinet. 2004;43(5):287–290.
8. Agranat I, Wainschtein SR. The strategy of enantiomer patents of drugs. Drug Discov Today. 2010;15(5-6):163–170.
9. Baumann P, Zullino DF, Eap CB. Enantiomers’ potential in psychopharmacology – a critical analysis with special emphasis on the antidepressant escitalopram. Eur Neuropsychopharmacol. 2002;12(5):433–444.
10. Nutt DJ, Feetam CL. What one hand giveth the other taketh away: some unpredicted effects of enantiomers in psychopharmacology. J Psychopharmacol. 2010;24(8):1137–1141.
11. Darwish M, Kirby M, Hellriegel ET, Robertson P. Armodafinil and modafinil have substantially different pharmacokinetic profiles despite having the same terminal half-lives: analysis of data from three randomized, single-dose, pharmacokinetic studies. Clin Drug Investig. 2009; 29(9):613–623.
12. Nishimura M, Sato K. Ketamine stereoselectively inhibits rat dopamine transporter. Neurosci Lett. 1999;274(2):131–134.
13. Pinto LR, Bittencourt LR, Treptow EC, Braga LR, Tufik S. Eszopiclone versus zopiclone in the treatment of insomnia. Clinics (Sao Paulo). 2016;71(1):5–9.
14. Greenblatt DJ, Zammit GK. Pharmacokinetic evaluation of eszopiclone: clinical and therapeutic implications. Expert Opin Drug Metab Toxicol. 2012;8(12):1609–1618.
15. Hyttel J, Bøgesø KP, Perregaard J, Sánchez C. The pharmacological effect of citalopram residues in the (S)-(+)-enantiomer. J Neural Transm Gen Sect. 1992;88(2):157–160.
16. Greenblatt DJ, Harmatz JS, Shader RI. Psychotropic drug prescribing in the United States: Extent, costs, and expenditures. J Clin Psychopharmacol. 2011;31(1):1–3.
17. Available at: http://www.data-rx.com. Accessed June 15, 2016.
18. von Moltke LL, Greenblatt DJ, Giancarlo GM, Granda BW, Harmatz JS, Shader RI. Escitalopram (S-citalopram) and its metabolites in vitro: cytochromes mediating biotransformation, inhibitory effects, and comparison to R-citalopram. Drug Metab Dispos. 2001;29(8):1102–1109.
19. Sidhu J, Priskorn M, Poulsen M, Segonzac A, Grollier G, Larsen F. Steady-state pharmacokinetics of the enantiomers of citalopram and its metabolites in humans. Chirality. 1997;9(7):686–692.
20. Zheng Z, Jamour M, Klotz U. Stereoselective HPLC-assay for citalopram and its metabolites. Ther Drug Monit. 2000;22(2):219–224.
21. Herrlin K, Yasui-Furukori N, Tybring G, Widén J, Gustafsson LL, Bertilsson L. Metabolism of citalopram enantiomers in CYP2C19/CYP2D6 phenotyped panels of healthy Swedes. Br J Clin Pharmacol. 2003;56(4):415–421.
22. Foglia JP, Pollock BG, Kirshner MA, Rosen J, Sweet R, Mulsant B. Plasma levels of citalopram enantiomers and metabolites in elderly patients. Psychopharmacol Bull. 1997;33(1):109–112.
23. Voirol P, Rubin C, Bryois C, Kosel M, Buclin T, Baumann P. Pharmacokinetic consequences of a citalopram treatment discontinuation. Ther Drug Monit. 1999;21(3):263–266.
24. Waugh J, Goa KL. Escitalopram: a review of its use in the management of major depressive and anxiety disorders. CNS Drugs. 2003;17(5):343–362.
25. Owens MJ, Knight DL, Nemeroff CB. Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biol Psychiatry. 2001;50(5):345–350.
26. El Mansari M, Sanchez C, Chouvet G, Renaud B, Haddjeri N. Effects of acute and long-term administration of escitalopram and citalopram on serotonin neurotransmission: an in vivo electrophysiological study in rat brain. Neuropsychopharmacology. 2005;30(7):1269–1277.
27. Le Poul E, Laaris N, Doucet E, Laporte AM, Hamon M, Lanfumey L. Early desensitization of somato-dendritic 5-HT1A autoreceptors in rats treated with fluoxetine or paroxetine. Naunyn Schmiedebergs Arch Pharmacol. 1995;352(2):141–148.
28. Sánchez C, Bergqvist PB, Brennum LT, et al. Escitalopram, the S-(+)-enantiomer of citalopram, is a selective serotonin reuptake inhibitor with potent effects in animal models predictive of antidepressant and anxiolytic activities. Psychopharmacology (Berl). 2003;167(4):353–362.
29. Zhong H, Haddjeri N, Sánchez C. Escitalopram, an antidepressant with an allosteric effect at the serotonin transporter–a review of current understanding of its mechanism of action. Psychopharmacology (Berl). 2012;219(1):1–13.
30. Ou JJ, Xun GL, Wu RR, et al. Efficacy and safety of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, randomized, double-blind, flexible dose study. Psychopharmacology (Berl). 2011;213(2-3):639–646.
31. Yevtushenko VY, Belous AI, Yevtushenko YG, Gusinin SE, Buzik OJ, Agibalova TV. Efficacy and tolerability of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, prospective, randomized, double-blind, active-controlled study in adult outpatients. Clin Ther. 2007;29(11):2319–2332.
32. Burke WJ, Gergel I, Bose A. Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J Clin Psychiatry. 2002;63(4):331–336.
33. Moore N, Verdoux H, Fantino B. Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder. Int Clin Psychopharmacol. 2005;20(3):131–137.
34. Lalit V, Appaya PM, Hegde RP, et al. Escitalopram versus citalopram and sertraline: a double-blind controlled, multi-centric trial in Indian patients with unipolar major depression. Indian J Psychiatry. 2004;46(4):333–341.
35. Colonna L, Andersen HF, Reines EH. A randomized, double-blind, 24-week study of escitalopram (10 mg/day) versus citalopram (20 mg/day) in primary care patients with major depressive disorder. Curr Med Res Opin. 2005;21(10):1659–1668.
36. Li H, Li T, Li G, Luo J. Citalopram and escitalopram in the treatment of major depressive disorder: a pooled analysis of 3 clinical trials. Ann Clin Psychiatry. 2014;26(4):281–287.
37. Alkhafaji AA, Trinquart L, Baron G, Desvarieux M, Ravaud P. Impact of evergreening on patients and health insurance: a meta-analysis and reimbursement cost analysis of citalopram/escitalopram antidepressants. BMC Med. 2012;10:142.
38. Trkulja V. Is escitalopram really relevantly superior to citalopram in treatment of major depressive disorder? A meta-analysis of head-to-head randomized trials. Croat Med J. 2010; 51(1):61–73.
39. Lepola U, Wade A, Andersen HF. Do equivalent doses of escitalopram and citalopram have similar efficacy? A pooled analysis of two positive placebo-controlled studies in major depressive disorder. Int Clin Psychopharmacol. 2004;19(3):149–155.
40. Azorin JM, Llorca PM, Despiegel N, Verpillat P. Escitalopram is more effective than citalopram for the treatment of severe major depressive disorder. Encephale. 2004;30(2):158–166.
41. Montgomery S, Hansen T, Kasper S. Efficacy of escitalopram compared to citalopram: a meta-analysis. Int J Neuropsychopharmacol. 2011;14(2):261–268.
42. Auquier P, Robitail S, Llorca PM, Rive B. Comparison of escitalopram and citalopram efficacy: A meta-analysis. Int J Psychiatry Clin Pract. 2003;7(4):259–268.
43. Bandelow B, Stein DJ, Dolberg OT, Andersen HF, Baldwin DS. Improvement of quality of life in panic disorder with escitalopram, citalopram, or placebo. Pharmacopsychiatry. 2007;40(4):152–156.
44. Sánchez C, Kreilgaard M. R-citalopram inhibits functional and 5-HTP-evoked behavioural responses to the SSRI, escitalopram. Pharmacol Biochem Behav. 2004;77(2):391–398.
45. Sánchez C, Gruca P, Papp M. R-citalopram counteracts the antidepressant-like effect of escitalopram in a rat chronic mild stress model. Behav Pharmacol. 2003;14(5-6):465–470.
46. Coleman JA, Green EM, Gouaux E. X-ray structures and mechanism of the human serotonin transporter. Nature. 2016;532(7599):334–339.
47. Plenge P, Gether U, Rasmussen SG. Allosteric effects of R- and S-citalopram on the human 5-HT transporter: evidence for distinct high- and low-affinity binding sites. Eur J Pharmacol. 2007;567(1–2):1–9.
48. Sánchez C, Bøgesø KP, Ebert B, Reines EH, Braestrup C. Escitalopram versus citalopram: the surprising role of the R-enantiomer. Psychopharmacology (Berl). 2004;174(2):163–176.
49. Sánchez C. The pharmacology of citalopram enantiomers: the antagonism by R-citalopram on the effect of S-citalopram. Basic Clin Pharmacol Toxicol. 2006;99(2):91–95.
50. Kasper S, Sacher J, Klein N, et al. Differences in the dynamics of serotonin reuptake transporter occupancy may explain superior clinical efficacy of escitalopram versus citalopram. Int Clin Psychopharmacol. 2009;24(3):119–125.
51. Braestrup C, Sánchez C. Escitalopram: a unique mechanism of action. Int J Psychiatry Clin Pract. 2004;8(Suppl 1):11–13.
52. Stórustovu S, Sánchez C, Pörzgen P, et al. R-citalopram functionally antagonises escitalopram in vivo and in vitro: evidence for kinetic interaction at the serotonin transporter. Br J Pharmacol. 2004;142(1):172–180.
53. Jacobsen JP, Plenge P, Sachs BD, et al. The interaction of escitalopram and R-citalopram at the human serotonin transporter investigated in the mouse. Psychopharmacology (Berl). 2014;231(23):4527–4540.
54. Available at: http://www.fda.gov/Drugs/DrugSafety/ucm297391.htm. Accessed July 9, 2016.
55. Chae YJ, Jeon JH, Lee HJ, et al. Escitalopram block of hERG potassium channels. Naunyn Schmiedebergs Arch Pharmacol. 2014;387(1):23–32.
56. Howland RH. A question about the potential cardiac toxicity of escitalopram. J Psychosoc Nurs Ment Health Serv. 2012;50(4):17–20.
57. Marcum ZA, Vande Griend JP, Linnebur SA. FDA drug safety communications: a narrative review and clinical considerations for older adults. Am J Geriatr Pharmacother. 2012;10(4):264–271.
58. Hutton LMJ, Cave AJ, St-Jean R, Banh HL. Should we be worried about QTc prolongation using citalopram? A review. J Pharm Pract. 2016 [Epub ahead of print].
59. Vieweg WV, Hasnain M, Howland RH, et al. Citalopram, QTc interval prolongation, and torsade de pointes. How should we apply the recent FDA ruling? Am J Med. 2012;125(9):859–868.