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Citalopram

Klassificering: C

Preparat: Cipramil, Cipramil®, Citalopram 2care4, Citalopram Actavis, Citalopram Alternova, Citalopram Arrow, Citalopram Bluefish, Citalopram BMM Pharma, Citalopram Ebb, Citalopram Hydrobromide, Citalopram Jubilant, Citalopram Lundbeck, Citalopram Mylan, Citalopram Orifarm, Citalopram Orion, Citalopram ratiopharm, Citalopram Sandoz, Citalopram STADA®, Citalopram Teva, Citalopram Vitabalans, Citalopram® CNSpharma

ATC kod: N06AB04

Substanser: citalopram, citalopramhydrobromid, citalopramhydroklorid

Sammanfattning

Studier på patienter med depression har visat varierande resultat i effekt av citalopram mellan könen.

Äldre patienter bör inte behandlas med doser över 20 mg citalopram på grund av risken för QT-förlängning och arytmi. Ökad QT-förlängning och kammartakykardi av typen Torsade de Pointes har rapporterats främst hos kvinnor med hypokalemi och andra hjärtsjukdomar.
 
Vid användning av högre doser citalopram bör risken för allvarlig kammartakykardi på grund av QT-förlängning beaktas hos äldre patienter, i synnerhet kvinnor.

Additional information

Pharmacokinetics and dosing

There are contradictory results from pharmacokinetic studies of citalopram (CIT) and escitalopram (S-CIT). No sex differences in the pharmacokinetics of the metabolites desmethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) have been shown.

For citalopram, AUC was shown to be 1.5–2 times higher in women than in men in three pharmacokinetic studies (in total32 patients) conducted by the original manufacturer. However, in five other pharmacokinetic studies (in total 114 patients) no sex differences were seen. Clinical studies (237 men, 338 women) showed no differences in citalopram concentration between men and women [1, 2]. Also in healthy volunteers, no differences in pharmacokinetics between men and women after a single dose of 20 mg citalopram were found [3].However, in a sample of patients taking citalopram (216 men, 300 women), the dose corrected citalopram concentration was found to be higher in men than women in the higher dose range, 70-200 mg citalopram daily. No difference in citalopram concentration was observed for the lower dose, 10-60 mg daily [4].In a TDM study (247 men, 502 women), women had higher dose corrected concentrations for citalopram and DCIT and also lower citalopram clearance than men (21.7 vs. 25.5 L/h). No differences were observed in DCIT to citalopram ratio [5]. Similar to this, another TDM study observed 25% higher citalopram and 9% higher escitalopram concentrations in women than men after receiving 20 mg citalopram daily or 10 mg escitalopram daily (1344 men, 2456 women) [6]. Contrary to these findings, another TDM study in psychiatric patients (57 men, 112 women) found no significant sex differences in pharmacokinetics for citalopram and the metabolite DCIT after a mean daily dose of 40 mg. [7].

For escitalopram, the concentrations of escitalopram and the metabolites DCIT and DDCIT were analyzed in patients (50 men, 105 women) with a median daily dose of 20 mg daily. No differences in dose-normalized concentrations were found. However, the DCIT/escitalopram ratio was higher in women (0.64 vs. 0.50) as well as the concentration-over-dose for DCIT variance (45% vs. 35%) [8]. According to the original manufacturers of citalopram and escitalopram, no dose adjustment based on sex is needed [1, 2].

Effects

The original manufacturers of citalopram and escitalopram report no relationship between treatment outcome and sex [1, 2]. However, results vary between clinical studies. The large STAR*D study of major depression (1043 men, 1833 women, age 18-75 years), showed that women had better self-rated response and remission than men after treatment with citalopram for 12–14 weeks [9]. However, another study in patients with major depression (96 men, 196 women) showed no sex differences in response or dropout rates after 5 weeks of treatment with citalopram dose of 40 mg daily [10].

Menopause was shown to be related to poorer treatment response in patients treated with different SSRIs including citalopram (59 men, 95 menopausal women, 147 non-menopausal women) [11]. In a small study in patients between 18–40 years (19 men, 25 women), depressed women treated with citalopram for 8 weeks showed better treatment response than men  [12].

For use of citalopram in alcohol dependence, a placebo-controlled study showed men to have a better outcome. After 12 weeks of treatment of citalopram 40 mg daily in patients with alcohol dependence (16 men, 15 women), the men reduced their average drinks per day by 44% compared to 27% for women [13].

Adverse effects

A general alert has been issued about older patients, especially older women,  and the risk of QT-prolongation when treated with citalopram doses above 20 mg daily [14, 15]. It is well described in cardiology reports that treatment with citalopram and escitalopram induces QT-prolongation and increases the risk of lethal ventricular tachycardia type “Torsade de Pointes” to a greater extent in women, especially with hypokalemia and/or heart diseases. Also, elderly women are at higher risk of citalopram-induced hyponatremia [16, 17].Restless legs syndrome induced by citalopram has been suggested to be associated with male sex (risk ratio 2.09 vs. 1.80) [18].In contrast to these findings, another clinical study reported no sex differences in overall serious adverse effects or psychiatric serious adverse effects [9].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Försäljning på recept

Fler kvinnor än män hämtade ut tabletter innehållande citalopram (ATC-kod N06AB04) på recept i Sverige år 2015, totalt 154 551 kvinnor och 71 457 män. Det motsvarar 32 respektive 15 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 85 år och äldre hos båda könen. I genomsnitt var tabletter innehållande citalopram dubbelt så vanligt hos kvinnor [19].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2013-05-06

Referenser

  1. CELEXA (citalopram). DailyMed [www]. US National Library of Medicine. [updated 2014-07-14, cited 2016-04-07]. länk
  2. LEXAPRO (escitalopram). DailyMed [www]. US National Library of Medicine. [updated 2014-10-31, cited 2016-04-07]. länk
  3. Fudio S, Borobia AM, Piñana E, Ramírez E, Tabarés B, Guerra P et al. Evaluation of the influence of sex and CYP2C19 and CYP2D6 polymorphisms in the disposition of citalopram. Eur J Pharmacol. 2010;626:200-4. PubMed
  4. Le Bloc'h Y, Woggon B, Weissenrieder H, Brawand-Amey M, Spagnoli J, Eap CB et al. Routine therapeutic drug monitoring in patients treated with 10-360 mg/day citalopram. Ther Drug Monit. 2003;25:600-8. PubMed
  5. Reis M, Lundmark J, Bengtsson F. Therapeutic drug monitoring of racemic citalopram: a 5-year experience in Sweden, 1992-1997. Ther Drug Monit. 2003;25:183-91. PubMed
  6. Reis M, Aamo T, Spigset O, Ahlner J. Serum concentrations of antidepressant drugs in a naturalistic setting: compilation based on a large therapeutic drug monitoring database. Ther Drug Monit. 2009;31:42-56. PubMed
  7. Leinonen E, Lepola U, Koponen H, Kinnunen I. The effect of age and concomitant treatment with other psychoactive drugs on serum concentrations of citalopram measured with a nonenantioselective method. Ther Drug Monit. 1996;18:111-7. PubMed
  8. Reis M, Chermá MD, Carlsson B, Bengtsson F, Task Force for TDM of Escitalopram in Sweden. Therapeutic drug monitoring of escitalopram in an outpatient setting. Ther Drug Monit. 2007;29:758-66. PubMed
  9. Young EA, Kornstein SG, Marcus SM, Harvey AT, Warden D, Wisniewski SR et al. Sex differences in response to citalopram: a STAR*D report. J Psychiatr Res. 2009;43:503-11. PubMed
  10. Hildebrandt MG, Steyerberg EW, Stage KB, Passchier J, Kragh-Soerensen P, Danish University Antidepressant Group. Are gender differences important for the clinical effects of antidepressants?. Am J Psychiatry. 2003;160:1643-50. PubMed
  11. Pinto-Meza A, Usall J, Serrano-Blanco A, Suárez D, Haro JM. Gender differences in response to antidepressant treatment prescribed in primary care Does menopause make a difference?. J Affect Disord. 2006;93:53-60. PubMed
  12. Berlanga C, Flores-Ramos M. Different gender response to serotonergic and noradrenergic antidepressants A comparative study of the efficacy of citalopram and reboxetine. J Affect Disord. 2006;95:119-23. PubMed
  13. Naranjo CA, Knoke DM, Bremner KE. Variations in response to citalopram in men and women with alcohol dependence. J Psychiatry Neurosci. 2000;25:269-75. PubMed
  14. Läkemedelsverket. Citalopram – sänkt maxdos rekommenderas. Nyhet 2011-10-27.
  15. FDA. FDA Drug Safety Communication: Revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses. 2012-03-28.
  16. Cipramil (citalopram). Summary of Product Characteristics. Medical Products Agency - Sweden. [updated 2016-01-04, cited 2016-04-04]. länk
  17. Cipralex (escitalopram). Summary of Product Characteristics. Medical Products Agency - Sweden. [updated 2016-01-29, cited 2016-04-04]. länk
  18. Baughman KR, Bourguet CC, Ober SK. Gender differences in the association between antidepressant use and restless legs syndrome. Mov Disord. 2009;24:1054-9. PubMed
  19. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2012 [cited 2013-04-08.] länk

Författare: Fadiea Al-Aieshy, Desirée Loikas

Faktagranskat av: Expertrådet för psykiatriska sjukdomar, Expertrådet för geriatriska sjukdomar, Ellen Vinge, Lars Lööf, Mia von Euler

Godkänt av: Karin Schenck-Gustafsson