, Volume 41, Issue 3, pp 450–477 | Cite as


A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Potential in Depressive Illness
  • Richard J. Milne
  • Karen L. Goa
Drug evaluation



Citalopram is an antidepressant belonging to a new class of drugs which enhance serotoninergic neurotransmission through potent and selective inhibition of serotonin reuptake. Preliminary trials suggest that its short term therapeutic efficacy is significantly greater than that of placebo and mianserin, and comparable to that of amitriptyline, maprotiline and imipramine. It appears to be a weaker antidepressant agent than clomipramine, but better tolerated. Its elimination half life of 33 hours permits once daily oral administration

Symptomatic improvement obtained with short term treatment has been maintained when therapy has been extended for up to 1 year; in the few patients studied for this extended period, the relapse rate was lower than with fluvoxamine, fluoxetine or imipramine

Compared to standard antidepressant agents, citalopram is well tolerated. It does not appear to be cardiotoxic, has not been associated with seizures in humans, and is relatively nonsedating. Unlike the tricyclic antidepressants, citalopram has minimal anticholinergic effects. Mild and transient nausea, with or without vomiting, is the most frequent adverse effect — occurring in 20% of patients — and increased perspiration, headache, dry mouth, tremor and insomnia are experienced by 15 to 18% of patients

Citalopram thus offers similar therapeutic efficacy and a more favourable tolerability profile than the tricyclic antidepressants. Preliminary data suggest that it may be particularly useful in patients who cannot tolerate the anticholinergic or cardiovascular side effects of tricyclic antidepressants and in those for whom sedation is not indicated

Pharmacodynamic Properties

Citalopram, like the other ‘second generation’ antidepressant agents fluvoxamine, fluoxetine and paroxetine, enhances serotoninergic neurotransmission through selective and potent inhibition of neuronal serotonin reuptake. Its major metabolites are weaker and less selective serotonin uptake blockers. In vitro, citalopram blocks serotonin uptake in platelets, synaptosomal preparations, and brain slices, and it competes with serotonin and imipramine for a common binding site. Citalopram has low affinity for a range of receptors including 5-HT1A, 5-HT1B, 5-HT2, dopamine1, dopamine2, α1-, α2-, β1-, β2-adreno, histamine1, benzodiazepine, opioid, muscarinic and monoamine oxidase inhibitor receptors

Pronounced inhibition of serotonin reuptake has been demonstrated in various species of animals at plasma citalopram concentrations less than 100 nmol/L. In vivo, citalopram and its main metabolite, demethyl-citalopram, antagonise displacement of serotonin, but not noradrenaline, by 4, α-dimethyl-metatyramine in the central nervous system, confirming citalopram’s selectivity for serotonin. In several animal models citalopram reduces serotonin turnover, presumably secondary to the increased intrasynaptic serotonin levels resulting from reuptake inhibition. The therapeutic effects of all antidepressants, including citalopram, develop over several weeks (see Therapeutic Use), possibly as a result of adaptive changes in receptors. Long term administration of citalopram ‘up-regulates’ α1-receptors and ‘down-regulates’ β2-receptors in rat cerebral cortex but not in thalamus or hippocampus. Unlike many other antidepressants, citalopram does not down-regulate the β-adrenoreceptor-coupled adenylate cyclase system

Like other antidepressants, citalopram prevents the immobility (‘behavioural despair’) induced by enforced swimming in rodents. In screening tests for central effects on monoaminergic mechanisms, citalopram prevents the hyperthermia induced by depletion of serotoninergic nerve terminals and enhances behaviours induced by administration of the serotonin precursor, 1-5-hydroxytryptophan. Citalopram potentiates morphine analgesia in rats probably via its effects on the serotoninergic component of morphine’s action. Unlike tricyclic antidepressants, citalopram does not reduce exploratory activity in rodents, and has little sedative effect in humans

At doses in dogs approximating usual clinical doses, citalopram is considered to have little convulsant potential. In contrast with tricyclic antidepressants, citalopram does not affect indices of cardiac conduction in dogs or cats, and does not induce orthostatic hypotension in humans. Neurohormonal effects of citalopram are largely uninvestigated

Pharmacokinetic Properties

Following oral administration of citalopram 50mg, peak plasma concentrations of 120 to 150 nmol/L are reached within 3 hours. Upon repeated daily oral administration, steady-state conditions are achieved in about 1 week. Doses in the range 30 to 60mg daily give rise to steady-state plasma concentrations of 120 to 600 nmol/L. About 50% of citalopram is bound to plasma proteins. In humans, the volume of distribution of citalopram is relatively large (14 L/kg). The elimination half-life of citalopram in healthy subjects is about 33 hours, thus once-daily administration is adequate to maintain steady-state concentrations

After a single oral dose of citalopram, about 12% is excreted unchanged in the urine. The major metabolite, demethyl-citalopram, is found in plasma in concentrations one-half to one-third that of the parent compound. Since this metabolite is 4 times less potent as a serotonin reuptake inhibitor, and less selective for serotonin than citalopram, it is unlikely to contribute substantially to the therapeutic effect of citalopram

Although pharmacokinetic data are not yet available for patients with known hepatic or renal impairment, in elderly patients daily doses of 20mg yielded plasma drug concentrations as much as 4 times higher than those expected for younger patients administered the same dose, implying lower clearance rates. Phenothiazines may impair hepatic metabolism of citalopram, and thereby raise plasma concentrations

Therapeutic Use

Citalopram is an effective antidepressant when administered in single daily doses of 40 to 60mg, usually orally, to patients with major depressive disorder. Noncomparative studies over 4 to 6 weeks have shown that citalopram produces marked improvement in 30 to 70% of patients, and moderate improvement in another 10 to 50%, using the Hamilton Depression, Montgomery-Asberg Depression Rating or Clinical Global Impression Scales. Small comparative studies indicate that it is more effective than placebo, and similar in efficacy to amitriptyline and maprotiline in alleviating symptoms of depressive illness, but possibly weaker than clomipramine and less effective in normalising sleep patterns. Therapeutic effects can be apparent within 1 week but the full effects take 4 to 6 weeks to develop. The therapeutic effects of citalopram appear more rapidly than those of mianserin but may develop more slowly than those of clomipramine. Controlled comparisons with other serotonin reuptake inhibitors such as paroxetine, fluvoxamine and fluoxetine are required to establish the relative efficacies


Compared with the standard tricyclics, citalopram is a relatively well tolerated antidepressant agent. It has not been associated with seizures or changes in pulse or blood pressure, and does not cause orthostatic hypotension. Citalopram is largely nonsedating and does not appear to stimulate appetite. Anticholinergic effects (dry mouth, constipation, difficulties in visual accommodation) are less common than with tricyclic antidepressants. The most commonly reported adverse effects associated with short term treatment are nausea and vomiting in 20% of patients, increased perspiration, headache and dry mouth (17% each), and tremor and insomnia (about 15% each). All adverse symptoms tend to reduce in frequency during medium to long term administration of citalopram

Dosage and Administration

The usual starting dose of citalopram in patients with depression is 20 or 40mg orally once daily. This may be titrated against efficacy and adverse events to 60mg over the first 1 to 3 weeks. In geriatric patients a steady-state dose of 20 to 30mg daily is more appropriate, and a correspondingly lower starting dose should be used. Citalopram may be administered in conjunction with a benzodiazepine if required to reduce anxiety or improve sleep. Lower starting doses of citalopram may be required when phenothiazines are coadministered


Fluoxetine Imipramine Fluvoxamine Clomipramine Mianserin 
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  1. Ahlfors UG, Elovaara S, Harma P, Suoniemi I, Heikkilä L, et al. Clinical multicentre study of citalopram compared double-blindly with mianserin in depressed patients in Finland. Nord Psykiatr Tidsskr 42: 201–210, 1988Google Scholar
  2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., APA Press, Washington DC, 1980Google Scholar
  3. Arnt J, Fredricson Overe K, Hyttel J, Olsen R. Changes in rat dopamine- and serotonin function in vivo after prolonged administration of the specific 5-HT uptake inhibitor, citalopram. Psychopharmacology 84: 457–465, 1984aPubMedGoogle Scholar
  4. Arnt J, Hyttel J, Larsen J-J. The citalopram/5-HTP-induced head shake syndrome is correlated to 5-HT2 receptor affinity and also influenced by other transmitters. Acta Pharmacologica et Toxicologica 55: 363–372, 1984bPubMedGoogle Scholar
  5. Baker PC, Goodrich CA. The effects of the specific uptake inhibitor Lu 10-171 (citalopram) upon brain indoleamine stores in the maturing mouse. General Pharmacology 13: 59–61, 1982PubMedGoogle Scholar
  6. Baker PC, Hoff KM. Indoleamine metabolism in maturing mouse brain following extended uptake inhibition with citalopram. General Pharmacology 18: 467–471, 1987PubMedGoogle Scholar
  7. Baron BM, Ogden A-M, Siegel BW, Stegeman J, Ursillo RC, et al. Rapid down regulation of β-adrenoceptors by co-administration of desipramine and fluoxetine. European Journal of Pharmacology 154: 125–134, 1988PubMedGoogle Scholar
  8. Bech P. Clinical properties of citalopram in comparison with other antidepressants: a quantitative meta-analysis. Abstract from XXII Nordiske Psykiater-Kongres, Reykjavik, 10–13 August, 1988. In Montgomery SA (Ed.) Citalopram: a new antidepressant from Lundbeck Research, pp. 56–68, Excerpta Medica, 1989Google Scholar
  9. Benfield P, Heel RC, Lewis SP. Fluoxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs 32: 481–508, 1986PubMedGoogle Scholar
  10. Benfield P, Ward A. Fluvoxamine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs 32: 313–334, 1986PubMedGoogle Scholar
  11. Beving H, Bjerkenstedt L, Malmgren R, Olsson P, Unge G. The effects of citalopram (Lu 10-171) on the serotonin (5-HT) uptake kinetics in platelets from endogenously depressed patients. Journal of Neural Transmission 61: 95–104, 1985PubMedGoogle Scholar
  12. Bjerkenstedt L, Edman G, Flyckt L, Hagenfeldt L, Sedvall G, et al. Clinical and biochemical effects of citalopram, a selective 5-HT reuptake inhibitor — a dose-response study in depressed patients. Psychopharmacology 87: 253–259, 1985aPubMedGoogle Scholar
  13. Bjerkenstedt L, Flyckt L, Fredricson Overa K, Lingjaerde O. Relationship between clinical effects, serum drug concentration and serotonin uptake inhibition in depressed patients treated with citalopram. A double-blind comparison of three dose levels. European Journal of Clinical Pharmacology 28: 553–557, 1985bPubMedGoogle Scholar
  14. Boeck V, Jørgensen A. Electrocardiographs and cardiovascular changes in cats and dogs caused by high doses of amitriptyline given as conventional tablets or a sustained release preparation. Acta Pharmacologica et Toxicologica 46: 161–170, 1980PubMedGoogle Scholar
  15. Boeck V, Jørgensen A, Fredricson Overe K. Comparative animal studies on cardiovascular toxicity of tri- and tetracyclic anti-depressants and citalopram; relation to drug plasma levels. Psychopharmacology 82: 275–281, 1984PubMedGoogle Scholar
  16. Boeck V, Fredricson Overe K, Syendsen O. Studies on acute toxicity and drug levels of citalopram in the dog. Acta Pharmacologica et Toxicologica 50(3): 169–174, 1982PubMedGoogle Scholar
  17. Bouchard JM, Delaunay J, Delisle JP, Grasset N, Mermberg PF, et al. Citalopram versus maprotiline: a controlled, clinical multicentre trial in depressed patients. Acta Psychiatrica Scandinavica 76: 583–592, 1987PubMedGoogle Scholar
  18. Brunello N, Riva M, Volterra A, Racagni G. Effect of some tricyclic and nontricyclic antidepressants on [3 H] imipramine binding and serotonin uptake in rat cerebral cortex after prolonged treatment. Fundamental Clinical Pharmacology 1: 327–333, 1987PubMedGoogle Scholar
  19. Buus-Larsen J. Potent and long lasting potentiation of two 5-hydroxytryptophan induced effects in mice by three selective 5HT uptake inhibitors. European Journal of Pharmacology 47: 351–358, 1978Google Scholar
  20. Byerley WF, McConnell EJ, McCabe RT, Dawson TM, Grosser BI, et al. Decreased beta-adrenergic receptors in rat brain after chronic administration of the selective serotonin uptake inhibitor fluoxetine. Psychopharmacology 94: 141–143, 1988PubMedGoogle Scholar
  21. Caccia S, Garattini S. Formation of active metabolites of psychotropic drugs. An updated review of their significance. Clinical Pharmacokinetics 18(6): 434–459, 1990PubMedGoogle Scholar
  22. Carlsson A, Lindqvist M. Effects of antidepressant agents on the synthesis of brain monoamines. Journal of Neural Transmission 43: 73–91, 1978PubMedGoogle Scholar
  23. Carney MWP, Roth M, Graside RF. The diagnosis of depressive syndromes and the prediction of ECT response. British Journal of Psychiatry 111: 659–674, 1965PubMedGoogle Scholar
  24. Chaput Y, de Montigny C, Blier P. Effects of a selective 5-HT reuptake blocker, citalopram, on the sensitivity of 5-HT autoreceptors: electrophysiological studies in the rat brain. Naunyn-Schmiedeberg’s Archives of Pharmacology 333: 342–348, 1986PubMedGoogle Scholar
  25. Charbonnier J-F, Reboul P, Rougier M, Aubin B, Chassaing JL, et al. Citalopram. An open trial of a highly selective 5-HT uptake inhibitor, administered intravenously to depressed patients. Encéphale 13: 249–254, 1987PubMedGoogle Scholar
  26. Christensen P, Thomsen HY, Pedersen OL, Gram LF, Kragh-Sørensen P. Orthostatic side effects of clomipramine and citalopram during treatment for depression. Psychopharmacology 86: 383–385, 1985PubMedGoogle Scholar
  27. Cooper JR, Bloom FE, Roth RH. The biochemical basis of neuropharmacology, Oxford University Press, New York, 1982Google Scholar
  28. Danish University Antidepressant Group. Citalopram: clinical effect profile in comparison with clomipramine. A controlled multicenter study. Psychopharmacology 90: 131–138, 1986Google Scholar
  29. D’Amato RJ, Largent BL, Snowman AM, Snyder SH. Selective labeling of serotonin uptake sites in rat brain by [3 H]citalopram contrasted to labeling of multiple sites by [3 H]imipramine. Journal of Pharmacology and Experimental Therapeutics 242: 364–371, 1987PubMedGoogle Scholar
  30. Daniel W, Melzacka M. The effect of antidepressants on ethylmorphine and imipramine N-demethylation in rat liver microsomes. Journal of Pharmacy and Pharmacology 38: 396–398, 1986PubMedGoogle Scholar
  31. de Wilde J, Mertens C, Fredricson Overe K, Hopfner Petersen HE. Citalopram versus mianserin. A controlled, double-blind trial in depressed patients. Acta Psychiatrica Scandinavica 72(1): 89–96, 1985PubMedGoogle Scholar
  32. Delini-Stula A. New pharmacological findings in depression. Psychopathology 19 (Suppl. 2): 94–102, 1986PubMedGoogle Scholar
  33. Dencker SJ, Hopfner Petersen HE. Side-effect profile of citalopram and reference antidepressants in depression. XXII Nordiske Psykiater-Kongres, Reykjavik, 10–13 August 1988. Pp. 31–42, 1989Google Scholar
  34. Drew R, Siddik ZH. Effect of a specific 5HT uptake inhibitor (citalopram) on drug accumulation by rat lung slices. Pharmacology 20(1): 27–31, 1980PubMedGoogle Scholar
  35. Dufour H, Bouchacourt M, Thermoz P, Viala A, Rop PP, et al. Citalopram — a highly selective 5-HT uptake inhibitor — in the treatment of depressed patients. International Clinical Psychopharmacology 2: 225–237, 1987PubMedGoogle Scholar
  36. File SE, Tucker JC. Behavioral consquences of antidepressant treatment in rodents. Neuroscience and Biobehavioral Reviews 10: 123–134, 1986PubMedGoogle Scholar
  37. Fjalland B. Influence of citalopram and chlorimipramine on uptake of 5-HT by isolated perfused guinea pig lungs. Acta Pharmacologica et Toxicologica 42(5): 377–380, 1978PubMedGoogle Scholar
  38. Fredericson Overa K, Toft B, Christophersen L, Gylding-Sabroe JP. Kinetics of citalopram in elderly patients. Psychopharmacology 86: 253–257, 1985Google Scholar
  39. Fredricson Overa K. Preliminary studies of the kinetics of citalopram in man. European Journal of Clinical Pharmacology 14(1): 69–73, 1978Google Scholar
  40. Fredricson Overø K. Fluorescence assay of citalopram and its metabolites in plasma by scanning densitometry of thin layer chromatograms. Journal of Chromatography 224: 256–331, 1981Google Scholar
  41. Fredricson Overa K. Kinetics of citalopram in man; plasma levels in patients. Progress in Neuro-Psychopharmacology and Biological Psychiatry 6: 311–318, 1982Google Scholar
  42. Fredricson Overa K. The pharmacokinetic and safety evaluation of citalopram from preclinical and clinical data. XXII Nor-diske Psykiater-Kongres, Reykjavik, 10–13 August 1988Google Scholar
  43. Fuller RW. Biochemical pharmacology of the serotonin system. Advances in Neurology 43: 469–480, 1986PubMedGoogle Scholar
  44. Galzin AM, Moret C, Verzier B, Langer SZ. Interaction between tricyclic and nontricyclic 5-hydroxytryptamine uptake inhibitors, and the presynaptic 5-hydroxytryptamine inhibitory autoreceptors in the rat hypothalamus. Journal of Pharmacology and Experimental Therapeutics 235: 200–211, 1985PubMedGoogle Scholar
  45. Garcha G, Smokcum RWJ, Stephenson JD, Weeramanthri TB. Effects of some atypical antidepressants on β-adrenoceptor binding and adenylate cyclase activity in the rat forebrain. European Journal of Pharmacology 108(1): 1–7, 1985PubMedGoogle Scholar
  46. Gastpar M, Gastpar G. Preliminary studies with citalopram (Lu 10-171), a specific 5-HT-reuptake inhibitor, as antidepressant. Progress in Neuro-Psychopharmacology and Biological Psychiatry 6: 319–325, 1982PubMedGoogle Scholar
  47. Górka Z, Maj J. Effects of repeated treatment with antidepressant drugs on the 24 hour behavior in the light-dark synchronized mice. Polish Journal of Pharmacology and Pharmacy 38: 493–499, 1986PubMedGoogle Scholar
  48. Gottlieb P, Wandall T, Fredricson Overa K. Initial, clinical trial of a new, specific 5-HT reuptake inhibitor, citalopram (Lu 10-171). Acta Psychiatrica Scandinavica 62(3): 236–344, 1980PubMedGoogle Scholar
  49. Graham D, Tahraoui L, Langer SZ. Effect of chronic treatment with selective monoamine oxidase inhibitors and specific 5-hydroxytryptamine uptake inhibitors on [3 H] paroxetine binding to cerebral cortical membranes of the fat. Neuropharma- cology 26: 1087–1092, 1987Google Scholar
  50. Gravem A, Amthor KF, Astrup C, Eigen K, Gjessing LR, et al. A double-blind comparison of citalopram (Lu 10-171) and amitriptyline in depressed patients. Acta Psychiatrica Scandinavica 75: 478–486, 1987PubMedGoogle Scholar
  51. Green AR, Nutt DJ. Antidepressants. In Grahame Smith & Cowen (Eds) Psychopharmacology 2, Part 1: preclinical psychopharmacology, pp. 1–34, Elsevier, Amsterdam, 1985Google Scholar
  52. Greenblatl DJ, Shader RI. On the psychopharmacology of beta-adrenergic blockade. Current Therapeutic Research 14: 615–625, 1972Google Scholar
  53. Gurney C. Diagnostic scales for affective disorders. Proceedings of 5th World Conference of Psychiatry, Mexico City, p. 130, 1971 Hall H, Ögren S-O. Effects of antidepressant drugs on histamine-H1 receptors in the brain. Life Sciences 34: 597–605, 1984Google Scholar
  54. Hall H, Sällemark M, Wedel I. Acute effects of atypical antidepressants on various receptors in the rat brain. Acta Pharmacologica et Toxicologica 54: 379–384, 1984PubMedGoogle Scholar
  55. Hamilton M. Development of a rating scale for primary depressive illness. British Journal of the Society of Clinical Psychologists 6: 278–296, 1967Google Scholar
  56. Hilakivi I, Kovala T, Leppävuori A, Shvaloff A. Effects of serotonin and noradrenaline uptake blockers on wakefulness and sleep in cats. Pharmacology and Toxicology 60: 161–166, 1987PubMedGoogle Scholar
  57. Hopfner Petersen HE. Medium-term efficacy of citalopram. Abstract. Scandinavian Society for Psychopharmacology Annual Meeting, Copenhagen, 1990Google Scholar
  58. Horodnicki JM, Czekalski S, Jarema M, Wdowiak J, Kubasiewicz A, et al. The therapeutical and endocrine effects of citalopram in patients with endogenous depression. 14th CINP Congress, Florence, Italy, June 19–23, 1984Google Scholar
  59. Humble M, Koczkas C, Norberg B, Larsson M, Oreland L, et al. Citalopram in panic disorder: clinical and biochemical effects. Scandinavian Society for Psychopharmacology Annual Meeting, Copenhagen, 1990Google Scholar
  60. Hyttel J. Citalopram: the pharmacological characteristics of the most selective inhibitor of serotonin uptake. XXII Nordiske Psykiater-Kongres, Reykjavik, 10–13 August 1988. Pp 11–21, 1989Google Scholar
  61. Hyttel J. Neurochemical characterization of a new potent and selective serotonin uptake inhibitor: Lu 10-171. Psychopharmacology 51(3): 225–233, 1977aPubMedGoogle Scholar
  62. Hyttel J. Effect of a selective 5-HT uptake inhibitor — Lu 10-171 — on rat brain 5-HT turnover. Acta Pharmacologica et Toxicologica 40(3): 439–446, 1977bPubMedGoogle Scholar
  63. Hyttel J. Effect of a specific 5-HT uptake inhibitor, citalopram (Lu 10-171), on 3 H-5-HT uptake in rat brain synaptosomes in vitro. Psychopharmacology 60: 13–18, 1978PubMedGoogle Scholar
  64. Hyttel J. Citalopram — pharmacological profile of a specific serotonin uptake inhibitor with antidepressant activity. Progress in Neuro-Psychopharmacology and Biological Psychiatry 6: 277–295, 1982PubMedGoogle Scholar
  65. Hyttel J, Fredricson Overa K, Amt J. Biochemical effects and drug levels in rats after long-term treatment with the specific 5-HT-uptake inhibitor, citalopram. Psychopharmacology 83: 20–27, 1984PubMedGoogle Scholar
  66. Hyttel J, Larsen J-J. Serotonin-selective antidepressants. Acta Pharmacologica et Toxicologica 56 (Suppl. 1): 146–153, 1985PubMedGoogle Scholar
  67. Itil TM, Menon GN, Bozak MM, Itil KZ. CNS effects of citalopram, a new serotonin inhibitor antidepressant (a quantitative pharmacoelectroencephalography study). Progress in Neuro-Psychopharmacology and Biological Psychiatry 8: 397–409, 1984PubMedGoogle Scholar
  68. Kopanski C, Türck M, Schultz JE. Effects of long-term treatment of rats with antidepressants on adrenergic-receptor sensitivity in cerebral cortex: structure activity study. Neurochemistry International 5: 649–659, 1983PubMedGoogle Scholar
  69. Korsgaard S, Noring U, Povlsen UJ, Gerlach J. Effects of citalopram, a specific serotonin uptake inhibitor, in tardive dyskinesia and Parkinsonism. Clinical Neuropharmacology 9: 52–57, 1986PubMedGoogle Scholar
  70. Kragh-Sorensen P, Fredricson Overa K, Petersen OL, Jensen K, Parnas W. The kinetics of citalopram: single and multiple dose studies in man. Acta Pharmacologica et Toxicologica 48(1): 53–60, 1981PubMedGoogle Scholar
  71. Lader M, Melhuish A, Frcka G, Fredricson Overa K, Christensen V. The effects of citalopram in single and repeated doses and with alcohol on physiological and psychological measures in healthy subjects. European Journal of Clinical Pharmacology 31(2): 183–190, 1986PubMedGoogle Scholar
  72. Langer SZ, Schoemaker H. Effects of antidepressants on monoamine transporters. Progress, in Neuro-Psychopharmacology and Biological Psychiatry 12: 193–216, 1988Google Scholar
  73. Larsen J-J, Arnt J. Reduction in locomotor activity of arthritic rats as parameter for chronic pain: effect of morphine, acetylsalicylic acid and citalopram. Acta Pharmacologica et Toxicologica 57(5): 345–351, 1985PubMedGoogle Scholar
  74. Larsen J-J, Christensén AV. Subarachnoidal administration of the 5-HT uptake inhibitor citalopram points to the spinal role of 5-HT in morphine antinociception. Pain 14: 339–345, 1982PubMedGoogle Scholar
  75. Lamelle M, Vanisberg M-A, Maloteaux J-M. Regional and sub-cellular localization in human brain of [3 H] paroxetine binding, a marker of serotonin uptake sites. Biological Psychiatry 24: 299–309, 1988Google Scholar
  76. Lemberger L, Fuller RW, Zerbe RL. Use of specific serotonin uptake inhibitors as antidepressants. Clinical Neuropharmacology 8: 299–317, 1985PubMedGoogle Scholar
  77. Lüllmann-Rauch R, Nässberger L. Citalopram-induced generalized lipidosis in rats. Acta Pharmacologica et Toxicologica 52(3); 161–167, 1983PubMedGoogle Scholar
  78. Lyby K, Elsborg L, Hopfner Petersen HE, Skoylund E. Long-term safety of citalopram. Abstract. XVIth CINP Congress, Munch, 1988Google Scholar
  79. Maj J, Rogóz Ż, Skuza G, Sowińska H. Reserpine-induced locomotor stimulation in mice chronically treated with typical and atypical antidepressants. European Journal of Pharmacology 87: 469–474, 1983aPubMedGoogle Scholar
  80. Maj J, Rogóz Ż, Skuza G, Sowińska H. The effect of selective inhibitors of noradrenaline and serotonin uptake on reserpine-and apomorphine-induced hypothermia in mice. Polish Journal of Pharmacology and Pharmacy 35: 49–57, 1983bPubMedGoogle Scholar
  81. Maj J, Rogóz Ż, Skuza G, Sowińska H. Repeated treatment with antidepressant drugs potentiates the locomotor response to (+)-amphetamine. Journal of Pharmacy and Pharmacology 36: 127–130, 1984aPubMedGoogle Scholar
  82. Maj J, Rogóz Ż, Skuza G, Sowińska H. Repeated treatment with antidepressafit drugs increases the behavioural response to apomorphine. Journal of Neural Transmission 60: 273–282, 1984bPubMedGoogle Scholar
  83. Malinge M, Bourin M, Colombel MC, Larousse C. Additive effects of clonidine and antidepressant drugs in the mouse forced-swimming test. Psychopharmacology 96: 104–109, 1988PubMedGoogle Scholar
  84. Melzacka M, Rurak A, Adamus A, Daniel W. Distribution of citalopram in the blood serum and in the central nervous system of rats after single and multiple dosage. Polish Journal of Pharmacology and Pharmacy 36: 675–682, 1984PubMedGoogle Scholar
  85. Mendels J. Clinical experience with serotonin reuptake inhibiting antidepressants. Journal of Clinical Psychiatry 48 (Suppl. 3): 26–30, 1987PubMedGoogle Scholar
  86. Mendels J, Fabre L, Kiev A. A double-blind placebo controlled study of citalopram in major depressive disorder. 30th Annual Meeting of New Clinical Drug Evaluation Unit, Florida, May 29–June 1, 1990Google Scholar
  87. Milne RJ, Gamble GD. Behavioural modification of bulbospinal serotonergic inhibition and morphine analgesia. Brain Research 521: 167–174, 1990PubMedGoogle Scholar
  88. Milne RJ, Gamble GD, Holford NHG. Behavioural tolerance to morphine analgesia is supraspinally mediated: a quantitative analysis of dose-response relationships. Brain Research 491: 316–327, 1989PubMedGoogle Scholar
  89. Montgomery SA, Åsberg M. A new depression scale designed to be sensitive to change. British Journal of Psychiatry 134: 382–389, 1979PubMedGoogle Scholar
  90. Naranjo CA, Sullivan JT, Sykora K. The serotonin uptake inhibitor citalopram attenuates ethanol intake. Clinical Pharmacology and Therapeutics 41(3): 266–274, 1987PubMedGoogle Scholar
  91. Nowak G, Przegalinski E. Effect of repeated treatment with antidepressant drugs and electroconvulsive shock (ECS) on [3 H] prazosin binding to different rat brain structures. Journal of Neural Transmission 71: 57–64, 1988PubMedGoogle Scholar
  92. Nyth A-L, Balldin J, Eigen K, Gottfries C-G. Behandling med Citalopram vid demens. Normalisering av DST. Nord Psykiatr Tidsskr 41: 423–430, 1987Google Scholar
  93. Nyth; A-L, Gottfries CG, Eigen K, Engedal K, Gilje K, et al. The clinical efficacy of citalopram in treatment of emotional disturbances in dementia disorders. A Nordic Multicentre Study. British Journal of Psychiatry, in press, 1990Google Scholar
  94. Øfsti E. Citalopram — a specific 5-HT-reuptake inhibitor — as an antidepressant drug: a phase II multicentre trial. Progress in Neuro-Psychopharmacology and Biological Psychiatry 6: 327–335, 1982PubMedGoogle Scholar
  95. Ortmann R, Waldmeier PC, Radeke E, Feiner A, Delini-Stula A. The effects of 5-HT uptake- and MAO-inhibitors on L-5-HTP-induced excitation in rats. Naunyn-Schmiedeberg’s Archives of Pharmacology 311: 185–192, 1980PubMedGoogle Scholar
  96. Ostrow D. The new generation antidepressants: promising innovations or disappointments? Journal of Clinical Psychiatry 36:25–30, 1985Google Scholar
  97. Øyehaug E, Østensen ET, Salvesen B. High-performance liquid Chromatographic determination of citalopram and four of its metabolites in plasma and urine samples from psychiatric patients. Journal of Chromatography-Biomedical Applications 308: 199–208, 1984aPubMedGoogle Scholar
  98. Øyehaug E, Eide G, Salvesen B. Effect of phenothiazines on citalopram steady-state kinetics in psychiatric patients. Nor Pharma Acta 46: 37–46, 1984bGoogle Scholar
  99. Pawlowski L. Different action of 5-hydroxytryptamine (5-HT) uptake inhibitors on fenfluramine- but not p-chloramphetamine-induced hyperthermia in rats. Journal of Pharmacy and Pharmacology 33: 538–540, 1981Google Scholar
  100. Pawlowski L. Amitriptyline and femoxetine, but not clomipramine or citalopram, antagonize hyperthermia induced by directly acting 5-hydroxytryptamine-like drugs in heat adapted rats. Journal of Pharmacy and Pharmacology 36: 197–199, 1984PubMedGoogle Scholar
  101. Pawlowski L, Nowak G, Górka Z, Mazela H. Ro 11-2465 (cyanimipramine), citalopram and their N-desmethyl metabolites: effects on the uptake of 5-hydroxytryptamine and noradrenaline in vivo and related pharmacological activities. Psycho-pharmacology 86: 156–163, 1985Google Scholar
  102. Pawlowski L, Mazela H. Effects of antidepressant drugs, selective noradrenaline- or 5-hydroxytryptamine urjtake inhibitors, on apomorphine-induced hypothermia in mice. Psychopharmacology 88: 240–246, 1986PubMedGoogle Scholar
  103. Pawlowski L, Nowak G. Biochemical and pharmacological tests for the prediction of ability of monoamine uptake blockers to inhibit the uptake of noradrenaline in-vivo: the effects of desipramine, maprotiline, femoxetine and citalopram. Journal of Pharmacy and Pharmacology 39: 1003–1009, 1987PubMedGoogle Scholar
  104. Pedersen OL, Kragh-Sørensen P, Bjerre M, Fredricson Overa K. Gram LF. Citalopram, a selective serotonin reuptake inhibitor: clinical antidepressive and long-term effect — a phase II study. Psychopharmacology 77: 199–204, 1982PubMedGoogle Scholar
  105. Plaznik A, Kostowski W. Modification of behavioral response to intra-hippocampal injections of noradrenaline and adrenoceptor agonists by chronic treatment with desipramine and citalopram: functional aspects of adaptive receptor changes. European Journal of Pharmacology 117(2): 245–252, 1985PubMedGoogle Scholar
  106. Plenge P, Mellerup ET. Antidepressive drugs can change the affinity of [3 H]imipramine and [3 H]paroxetine binding to platelet and neuronal membranes. European Journal of Pharmacology 119: 1–8, 1985PubMedGoogle Scholar
  107. Porsolt RD, Anton G, Blavet N, Daniel M, Jalfre M. Behavioural despair in rats: a new model sensitive to antidepressant treatments. European Journal of Pharmacology 47: 379–391, 1978PubMedGoogle Scholar
  108. Porsolt RD, Le Pichon M, Jalfre M. Depression: a new animal model sensitive to antidepressant treatments. Nature 266: 730, 1977PubMedGoogle Scholar
  109. Richelson E, Nelson A. Antagonism by antidepressants of neuro-transmitter receptors of normal human brain in vitro. Journal of Pharmacology and Experimental Therapeutics 230: 94–102, 1984PubMedGoogle Scholar
  110. Richelson E, Pfenning M. Blockade by antidepressants and related compounds of biogenic amine uptake into rat brain synaptosomes: most antidepressants selectively block norepine-phrine uptake. European Journal of Pharmacology 104: 277–286, 1984PubMedGoogle Scholar
  111. Ropert R, Lôo H, Gay C. Preliminary open trial with a new antidepressant compound: citalopram. Encéphale 10: 131–134, 1984PubMedGoogle Scholar
  112. Rudorfer MV, Potter WZ. Antidepressants. A comparative review of the clinical pharmacology and therapeutic use of the ‘newer’ versus the ‘older’ drugs. Drugs 37: 713–738, 1989PubMedGoogle Scholar
  113. Schmauss M, Dieterle D, Albus M. Citalopram, a specific 5HT reuptake inhibitor, in severely depressed inpatients: an early clinical trial. Current Therapeutic Research 37: 1104–1112, 1985Google Scholar
  114. Shaw DM, Thomas DR, Briscoe MH, Watkins SE, Crimmins R. A comparison of the antidepressant action of citalopram and amitriptyline. British Journal of Psychiatry 149: 515–517, 1986PubMedGoogle Scholar
  115. Sugrue MF. Antagonism of fenfluramine-induced hyperthermia in rats by some, but not all, selective inhibitors of 5-hydroxytryptamine uptake. British Journal of Pharmacology 81: 651–657, 1984PubMedGoogle Scholar
  116. Sulser F. Antidepressant drug research: its impact on neurobiology and psychobiology. Adv. Biochem. Psychopharmacol., 1982, 31 (Typical and atypical Antidepressants: molecular mechanisms), 1–20Google Scholar
  117. Testa R, Angelico P, Abbiati GA. Effect of citalopram, amineptine, imipramine and nortriptyline on stress-induced (foot-shock) analgesia in rats. Pain 29: 247–255, 1987PubMedGoogle Scholar
  118. Timmerman L, De Beurs P, Tan BK, Leijnse-Ybema H, Sanchez C, et al. A double-blind comparative clinical trial of citalopram vs maprotiline in hospitalized depressed patients. International Clinical Psychopharmacology 2: 239–253, 1987PubMedGoogle Scholar
  119. Tucker JC, File SE. The effects of tricyclic and ‘atypical’ anti-depressants on spontaneous locomotor activity in rodents. Neuroscience and Biobehavioral Reviews 10: 115–121, 1986PubMedGoogle Scholar
  120. Vetulani J, Antkiewicz-Michaluk L, Rokosz-Pelc A. Chronic administration of antidepressant drugs increases the density of cortical [3 H]prazosin binding sites in the rat. Brain Research 310: 360–362, 1984aPubMedGoogle Scholar
  121. Vetulani J, Antkiewicz-Michaluk L, Rokosz-Pelc A, Pile A. Alpha up — beta down adrenergic regulation: a possible mechanism of action of antidepressant treatments. Polish Journal of Pharmacology and Pharmacy 36: 231–248, 1984bPubMedGoogle Scholar
  122. Vetulani J, Sulser F. Action of various antidepressant treatments reduces reactivity of noradrenergic cyclic AMP-generating system in limbic forebrain. Nature (London) 257: 495–496, 1975Google Scholar

Copyright information

© Adis International Limited 1991

Authors and Affiliations

  • Richard J. Milne
    • 1
  • Karen L. Goa
    • 1
  1. 1.Adis Drug Information ServicesAucklandNew Zealand

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