Citalopram: Clinical effect profile in comparison with clomipramine. A controlled multicenter study

Abstract

The selective serotonin reuptake inhibitor citalopram was compared with clomipramine in a multicenter clinical study. From a total of 150 depressed patients (age 18–65 years), 114 patients with a Hamilton Depression Scale (HDS) total score≧18 at the end of a 1 week placebo period were started on treatment with either citalopram (40 mg/day) or clomipramine (150 mg/day) (fixed, single daily dose). Patients stratified according to diagnostic rating (Newcastle Inventory, endogenous/non-endogenous) were randomly allocated to treatment groups using double blind principles. In total, 102 patients completed more than 2 weeks, treatment and were included in the analyses of therapeutic effect. The two drug groups were comparable in terms of sex, age, and departmental distribution.

Categorical measurements of therapeutic effect based on the HDS total score showed that in the endogenously depressed patients a significantly higher percentage of patients on clomipramine (n=37) than on citalopram (n=38) were classified as complete responders (HDS total≦7) after 3, 4 and 5 weeks of treatment. In the non-endogenously depressed patients (clomipramine: n=15, citalopram: n=12) rather similar numerical differences were observed (P<0.05 at 5th week). In the total patient group the percentage of complete response after 5 weeks was about 60 in the clomipramine group (n=52) and about 30 in the citalopram group (n=50) (P<0.005). The better effect of clomipramine seemed to be related in particular to the sleep items, but other items covering depression, retardation and anxiety/agitation also contributed to the difference in total score that was also seen in patients with low initial scores on the sleep items.

Citalopram was devoid of the typical autonomic side effects and orthostatic hypotension seen with clomipramine. Symptoms of nausea/vomiting and headache became somewhat worse in the citalopram- and somewhat better in the clomipramine-treated patients.

Participating centers: 1Department of Psychiatry, Odense University Hospital, Odense, 2Department of Psychiatry, Rigshospitalet, University of Copenhagen, Copenhagen, 3Departments of Psychiatry, Frederiksborg General Hospital, Hillerød, 4Department A and C, Psychiatric University Hospital, Århus, 5Department of Psychiatry, Bornholm General Hospital, Rønne, 6Department of Clinical Pharmacology, Odense University, Odense

Participating clinicians: J. Andersen2, P. Bech2,3, S. Benjaminsen1, M. Bjerre1, S. Bøjholm5, P. Christensen1, A. Gjerris2, L. Hansted4, E. Jensen3, P. Kragh-Sørensen1, C.B. Kristensen1,3, P. Kyneb4, D. Loldrup3, O.F. Madsen4, O.L. Pedersen1, O.J. Rafaelsen2, S. Rasmussen3, N. Reisby4, F. Sevaj3, P. Simonsen4, H.Y. Thomsen1, P. Vestergaard4

Coordination and drug assay: L.F. Gram6

Statistical consultants: O. Aaskoven, P. Allerup

Data-collection and -processing: C. Sánchez

Steering Committee: P. Bech, L.F. Gram (chairman), P. Kragh-Sørensen, O.J. Rafaelsen, N. Reisby, P. Vestergaard

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References

  1. Åsberg M, Cronholm B, Sjöqvist F, Tuck D (1970) Correlation of subjective side effects with plasma concentrations of nortriptyline. Br Med J 4:18–21

    Google Scholar 

  2. Bartko II, Carpenter WT (1976) On the methods and theory of reliability. J Nerv Ment Dis 163:307–317

    CAS  PubMed  Google Scholar 

  3. Bech P, Rafaelsen OJ (1980) The use of rating scales exemplified by a comparison of the Hamilton and the Bech-Rafaelsen Melancholia Scale. Acta Psychiatr Scand, Suppl 285, 62:128–132

    Google Scholar 

  4. Bech P, Gram LF, Dein E, Jacobsen O, Vitger J, Bolwig TG (1975) Quantitative rating of depressive states. Correlation between clinical assessment, self rating scale (Beck's Depression Inventory), and objective rating scale (Hamilton). Acta Psychiatr Scand 51:161–170

    Google Scholar 

  5. Bech P, Gram LF, Reisby N, Rafaelsen OJ (1980) The WHO depression Scale; Relationship to the Newcastle Scale. Acta Psychiatr Scand 62:140–153

    Google Scholar 

  6. Bech P, Allerup P, Gram LF, Reisby N, Rosenberg R, Jacobsen O, Nagy A (1981) The Hamilton depression scale; evaluation of specific objectivity using the Rasch-models. Acta Psychiatr Scand 62:140–153

    Google Scholar 

  7. Bech P, Allerup P, Reisby N, Gram LF (1984) Assessment of symptom change from improvement curves on the Hamilton Depression Scale in trials with antidepressants. Psychopharmacology 84:276–281

    Google Scholar 

  8. Bech P, Haaber A, Joyce CRB, Danish University Antidepressant Group (1986) Observation and judgement in psychiatry: profiled analyses in the assessment of depression. Psychol Med (in press)

  9. Bjerkenstedt L, Flyckt L, Fredricson Overø K, Lingjærde O (1985) Relationship between clinical effects, serum drug concentration and serotonin uptake inhibition in depressed treated with citalopram. A double-blind comparison of three dose levels. Eur J Clin Phyramcol 28:553–559

    Google Scholar 

  10. Carney MWP, Roth M, Graside RF (1965) The diagnosis of depressive syndromes and the prediction of ECT response. Br J Psychiatry 111:659–674

    Google Scholar 

  11. Christensen P, Thomsen HY, Pedersen OL, Gram LF, Kragh-Sørensen P (1985) Orthostatic side effects of clomipramine and citalopram during treatment for depression. Psychoparmacology 86:383–385

    Google Scholar 

  12. Cronholm B, Ottosson J-O (1960) Experimental studies of the therapeutic action of electroconvulsive therapy in endogenous depression. The role of the electrical stimulation and of the seizure discharge. Acta Psychiatr Neurol Scand Suppl 145:69–97

    Google Scholar 

  13. Delini-Stula A (1983) Mode of action of antidepressant drugs — primary effects. In: Angst J (ed) The origins of depression: current concepts and approaches. Springer-Verlag, Berlin, Heidelberg, pp 351–365

    Google Scholar 

  14. Della Corte L, Broadhurst AD, Scaragli GP, Filippini S, Heeley AF, James HD, Faraveli C, Pazzagli A (1979) Clincal response and tricyclic plasma levels during treatment with clomipramine. Br J Psychiatry 134:390–400

    Google Scholar 

  15. Gottlieb P, Wandall T, Fredricson Overø K (1980) Initial, clinical trial of a new, specific 5-HT reuptake inhibitor, citalopram (LU 10–171). Acta Psychiatr Scand 62:236–244

    Google Scholar 

  16. Gram LF (1983) Receptors, pharmacokinetics and clinical effects. In: Burrows GD, Norman T, Davis B (eds) Drugs and psychiatry, vol I, Antidepressants. Elsevier/North-Holland Biomedical Press BV, Amsterdam, pp 81–96

    Google Scholar 

  17. Gram LF, Reisby N, Ibsen I, Nagy A, Dencker SJ, Bech P, Petersen GO, Christiansen J (1976) Plasma levels and antidepressive effect of imipramine. Clin Pharmacol Ther 19:318–324

    Google Scholar 

  18. Gram LF, Bjerre M, Kragh-Sørensen P, Kvinesdal B, Molin J, Pedersen OL, Reisby N (1983) Imipramine metabolites in blood of patients during therapy and after overdose. Clin Pharmacol Ther 33:335–342

    Google Scholar 

  19. Gram LF (1984) Clinical studies with femoxetin: a critical review. In: Racagni G, Paoletti R, Kielholtz P (eds) Proceedings of the 14th CINP Congress. Clin Neuropharmacol col 7, Suppl 1. Raven Press, New York, pp 872–873

    Google Scholar 

  20. Gurney C (1971) Diagnostic scales for affective disorders. Proc 5th World Conference of Psychiatry, Mexico City, p 130

  21. Hamilton M (1967) Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6:278–296

    CAS  PubMed  Google Scholar 

  22. Hyttel J (1984) Experimental pharmacology of selective 5-HT reuptake inhibitors: Differences and similarities. In: Racagni G, Paoletti R, Kielholtz P (eds) Proceedings of the 14th CINP Congress. Clin Neuropharmacol vol 7, Suppl 1. Raven Press, New York, pp 866–867

    Google Scholar 

  23. Kragh-Sørensen P, Christensen P, Gram LF, Kristensen CB, Pedersen OL (1983) Phase-4 studies in psychopharmacology. New antidepressants. In: Gram LF et al. (eds) Clinical pharmacology in psychiatry. Bridging the experimental therapeutic gap. MacMillan, London, pp 114–125

    Google Scholar 

  24. Kragh-Sørensen P, Honoré PL, Gram LF (1986) Therapeutic comparison of selective 5-HT reuptake inhibitors with tricyclic antidepressants. In: Dahl SG, Gram LF, Paul SM, Potter WZ (eds) Clinical pharmacology in psychiatry: Selectivity in drug action, promises or problems? Springer-Verlag, Heidelberg (in press)

    Google Scholar 

  25. Nagy A, Treiber L (1973) Quantitative determination of imipramine and desipramine in human blood plasma by direct densitometry of thin-layer chromatograms. J Pharm Pharmacol 25:599–603

    Google Scholar 

  26. Pedersen OL, Kragh-Sørensen P, Bjerre M, Fredricson Overø K, Gram LF (1982) Citalopram, a selective serotonin reuptake inhibitor; clinical antidepressive and long term effect — a phase II study. Psychopharmacology 77:199–204

    Google Scholar 

  27. Reisby N, Gram LF, Bech P, Sihm F, Krautwald O, Elley J, Ortmann J, Christiansen J (1979) Clomipramine: plasma levels and clinical effects. Commun Psychopharmacol 3:341–351

    Google Scholar 

  28. Sugrue MF (1981) Current concepts on the mechanisms of action of antidepressant drugs. Pharmacol Ther 13:219–247

    Google Scholar 

  29. Thayssen P, Bjerre M, Kragh-Sørensen P, Møller M, Pedersen OL, Kristensen CB, Gram LF (1981) Cardiovascular effects of imipramine and nortriptyline in elderly patients. Psychopharmacology 74:360–364

    Google Scholar 

  30. Träskman L, Åsberg M, Bertilsson L, Cronholm B, Mellström B, Neckers LM, Sjöqvist F, Thorén P, Tybring G (1979) Plasma levels of clomipramine and its demethyl metabolite during treatment of depression. Clin Pharmacol Ther 26:600–610

    Google Scholar 

  31. Vandel B, Vandel S, Jounet JM, Allers G, Volmat R (1982) Relationship between the plasma concentration of clomipramine and desmethylclomipramine in depressive patients and the clinical response. Eur J Clin Pharmacol 22:15–20

    Google Scholar 

  32. Zis AP, Goodwin FK (1979) Novel antidepressants and the biogenic amine hypothesis of depression. Arch Gen Psychiatry 36:1097–1107

    Google Scholar 

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Danish University Antidepressant Group

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Gram, L.F. Citalopram: Clinical effect profile in comparison with clomipramine. A controlled multicenter study. Psychopharmacology 90, 131–138 (1986). https://doi.org/10.1007/BF00172884

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Key words

  • Citalopram
  • Clomipramine
  • Serotonin-reuptake
  • Depression
  • Antidepressants