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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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
Bartko II, Carpenter WT (1976) On the methods and theory of reliability. J Nerv Ment Dis 163:307–317
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
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
Bech P, Gram LF, Reisby N, Rafaelsen OJ (1980) The WHO depression Scale; Relationship to the Newcastle Scale. Acta Psychiatr Scand 62:140–153
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
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
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)
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
Carney MWP, Roth M, Graside RF (1965) The diagnosis of depressive syndromes and the prediction of ECT response. Br J Psychiatry 111:659–674
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
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
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
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
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
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
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
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
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
Gurney C (1971) Diagnostic scales for affective disorders. Proc 5th World Conference of Psychiatry, Mexico City, p 130
Hamilton M (1967) Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6:278–296
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
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
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)
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
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
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
Sugrue MF (1981) Current concepts on the mechanisms of action of antidepressant drugs. Pharmacol Ther 13:219–247
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
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
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
Zis AP, Goodwin FK (1979) Novel antidepressants and the biogenic amine hypothesis of depression. Arch Gen Psychiatry 36:1097–1107
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