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Moclobemide in Elderly Patients with Cognitive Decline and Depression: An International Double-blind, Placebo-controlled Trial

Published online by Cambridge University Press:  02 January 2018

M. Roth ,
C. Q. Mountjoy ,
R. Amrein  and
The International Collaborative Study Group
M. Roth*
Affiliation:
University of Cambridge Medical School
C. Q. Mountjoy
Affiliation:
St Andrew's Hospital, Northampton NN1 5DG
R. Amrein
Affiliation:
Department of Clinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland
*
Sir Martin Roth, Trinity College, Cambridge CB2 17Q. Fax: 01223 412193
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Abstract

Background

The new reversible MAOI moclobemide was compared with placebo in the treatment of elderly patients with DSM–III diagnosis of dementia and/or of major depression.

Method

Six hundred and ninety-four elderly patients with symptoms of depression and cognitive decline entered an international, multi-centre, double blind trial in which they were randomly allocated to treatment with either moclobemide 400 mg daily or placebo for 42 days. Five hundred and eleven patients met DSM–III criteria for dementia and were also depressed (DEM+D); 183 did not meet DSM–III criteria for dementia but met the criteria for DSM–III major depressive episode and also suffered from cognitive decline (MDE+CD).

Results

Analysis of the 17 and 24-item Hamilton Depression Scale scores showed that moclobemide, compared with placebo, produced significantly greater improvement in both the demented and depressed groups (P = 0.001 both diagnostic groups). There was an improvement in cognitive function as measured by the SCAG Factor 1 in moclobemide treated patients (P = 0.005 DEM+D; P = 0.02 MDE+CD). There was no evidence of decline in cognitive function as the result of treatment Clinical global assessment of tolerance was ‘excellent’ and ‘good’ in 88% of the moclobemide and in 92% of the placebo treated patients. The proportion of patients discontinuing treatment prematurely was similar in both treatment groups. There were no significant differences in side-effects between treatment groups. There were no significant changes in vital signs, ECG or laboratory findings in either treatment group. There were no dietary restrictions and no report of any tyramine reaction.

Conclusions

Moclobemide was shown to be a safe, well tolerated and effective antidepressant, which did not cause impairment of cognitive function in elderly patients with a DSM–III diagnosis of dementia and/or DSM–III major depression.

Type
Papers
Information
The British Journal of Psychiatry , Volume 168 , Issue 2 , February 1996 , pp. 149 - 157
Copyright
Copyright © 1996 The Royal College of Psychiatrists 

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Footnotes

1.

Drs: Baumhackl1, Hebenstreit2, Hinterhuber3, Katschnig4, König5, Pfolz6, Radmayr7, Rieder8, Saletu9, Schnaberth10, Schony11, (Austria); Botte12, Dierick13, Evrard14, Troisfontaines15, van Audenrode16 (Belgium); Hugonot17, Piette18 (France); [Benkert, Schlege19] Bergener20, Kanowski21, Kummer22, Vogel23 (Germany); Petursson24 (Iceland); Ginath25, Grüner26, Klein27 (Israel); Casacchia28, Cassano29, Gentili30, Martucci31, Ravizza32 (Italy); Boon33, Sleats34, van Tilburg35 (Netherlands); Baumgartner36, Kasas37, [Krebs, Poldinger38] Mohr39, Richard40, [Staehelin’ Zmilacher41] (Switzerland).

References

Altamura, A. C., Mauri, M. C., Rudas, N., et al (1989) Clinical activity and totanability of trazodone, mianserin, and amitriptyline in elderly subjects with major depression: a controlled multicenter trial. Clinical Neuropharmacology, 12 (suppl. 1), S25–S33: S34–S37.CrossRefGoogle ScholarPubMed
American Psychiatric Association (1980) Diagnostic and Statistical Manual of Mental Disorders (3rd edn) (DSM–III). Washington, DC: APA.Google Scholar
Bakish, D., Bradwein, J., Nair, N., et al (1992) A comparison of moclobemide, amitriptyline and placebo in depression: a Canadian multicenter study. Psychopharmacology, 106 (suppl.), S98–101.CrossRefGoogle Scholar
Baumhackl, U., Bizière, K., Fischbach, R., et al (1989) Efficacy and tolerability of moclobemide compared with imipramine in depressive disorder (DSM–III): An Austrian double-blind, multicentre study. British Journal of Psychiatry; 155 (suppl. 6), 78–83.CrossRefGoogle Scholar
Beaumont, G. & Hetzel, W. (1992) Patients at risk of suicide and overdose. Psychopharmacology, 106 (suppl.), S123–126.Google Scholar
Bocksberger, J. P., Gachoud, J. P., Richard, J., et al (1993) Comparison of the efficacy of moclobemide and fluvoxamine in elderly patients with a severe depressive episode. European Psychiatry, 8, 319–324.Google Scholar
Branconnier, R. J., Cole, J. O., Ghazvinian, S., et al (1982) Treating the depressed elderly patient: the comparative pharmacology of mianserin and amitriptyline. Advances in Biochemical Psychopharmacology, 32, 195–212.Google ScholarPubMed
Casacchia, M., Carolei, A., Barba, C., et al (1984) A placebo-controlled study of the antidepressant activity of moclobemide, a new MAO-A inhibitor. Pharmacopsychiatry, 17, 122–125.Google Scholar
Da Prada, M., Kettler, R., Keller, H. H., et al (1989) Neurochemical profile of moclobemide, a short-acting and reversible inhibitor of monamine oxidase type A. Journal of Pharmacology and Experimental Therapeutics, 248, 401–414.Google Scholar
De Vanna, M., Kummer, J., Agnoli, A., et al (1990) Moclobemide compared with second-generation antidepressants in elderly people. Acta Psychiatrica Scandinavica, (suppl. 160), 64–66.CrossRefGoogle Scholar
Folstein, M. F., Folstein, S. E. & McHugh, P. R. (1975) ‘Mini Mental State’: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198.Google Scholar
Folstein, M. F., & McHugh, P. R. (1978) The dementia syndrome of depression. In Alzheimer's Disease: Senile Dementia and Related Disorders (Aging, Vol. 7) (eds Katzman, R., Terry, R. D. & Bick, K. L.) New York: Raven Press.Google Scholar
Forsell, Y., Jorm, A. F., Fratiglioni, L., et al (1993) Application of DSM–III–R Criteria for major depressive episode to elderly subjects with and without dementia. American Journal of Psychiatry, 150, 1199–1202.Google Scholar
Friedel, R. O. (1978) Pharmacokinetics in the geropsychiatric patient. In Psychopharmacology, A Generation of Progress (eds Lipton, M. A., DiMascio, A. & Killam, K. F.), pp. 1499–1505. New York: Raven Press.Google Scholar
Gerson, S. C., Plotkin, D. A. & Jarvik, L. F. (1988) Antidepressant drug studies, 1964–1986: empirical evidence for aging patients. Journal of Clinical Psychopharmacology, 8, 311–322.Google Scholar
Gottfries, C. G., Brane, G., Gullberg, B., et al (1982) A new rating scale for dementia syndromes. Archives of Gerontology and Geriatrics, 1, 311–330.CrossRefGoogle ScholarPubMed
Guentert, T. W., Banken, L., Hilton, S., et al (1995) Moclobemide: Relationships between dose, drug concentration in plasma, and occurrence of adverse events. Journal of Clinical Psychopharmacology, 15, (suppl. 2), S84–94.CrossRefGoogle ScholarPubMed
Gurland, B. J. (1980) The epidemiology of depression and dementia in the elderly; the use of multiple indicators of these conditions. In Psychopathology in the Aged (eds Cole, J. O. & Barrett, J. E.), pp. 37–60. New York: Raven Press.Google Scholar
Hamilton, M. (1976) Hamilton Depression Scale. In ECDEU Assessment Manual for Psychopharmacology, Revised Edition (ed. Guy, W.), pp. 179–192. Rockville, Maryland: National Institute of Mental Health.Google Scholar
Hindmarch, I. & Kerr, J. (1992) Behavioural toxicity of antidepressants with particular reference to moclobemide. Psychopharmacology, 106 (suppl.), S49–55.CrossRefGoogle ScholarPubMed
Jauch, R., Griesser, E., Oesterhelt, G., et al (1990) Biotransformation of moclobemide in humans. Acta Psychiatrica Scandinavica, (suppl. 360), 87–90.CrossRefGoogle Scholar
Kam van der, P., Mol, F. & Wimmers, M. F. H. C. (1986) Beurteilungsskala für geriatrische patienten (BGP). In CIPS Collegium Internationale Psychiatriae Scalarum (Ed): Internationale Skalen für Psychiatrae Beltz. Google Scholar
Katz, I. R., Simpson, G. M., Curlik, S. M., et al (1990) Pharmacologic treatment of major depression for elderly patients in residential care settings. Journal of Clinical Psychiatry, 51, (suppl. 7), 41–47.Google Scholar
Kay, D. W. K., Beamish, P., & Roth, M. (1964) Old-age mental disorders in Newcastle upon Tyne, part 1, a study of prevalence. British Journal of Psychiatry, 110, 146–158.CrossRefGoogle Scholar
Knegterjng, H., Euck, M. & Huijsman, A. (1994) Effects of antidepressants on cognitive functioning of elderly patients. Drugs & Aging, 5, 192–199.Google Scholar
Lazarus, L. W., Newton, N., Cohler, B., et al (1987) Frequency and presentation depressive symptoms in patients with primary degenerative dementia. American Journal of Psychiatry, 144, 41–45.Google Scholar
Lauter, H. & Dame, S. (1991) Depressive disorders and dementia: the clinical view. Acta Psychiatrica Scandinavica, (suppl. 366), 40–46.CrossRefGoogle Scholar
Montgomery, S. A. & Åsberg, M. (1979) A new depression scale designed to be sensitive to change. British Journal of Psychiatry, 134, 381–389.Google Scholar
Nyth, A. L., Gottfries, C. G., Lyby, K., et al (1992) A controlled multicenter clinical study of citalopram and placebo in elderly depressed patients with and without concomitant dementia. Acta Psychiatrica Scandinavica, 86, 138–145.CrossRefGoogle ScholarPubMed
Plotkjn, D. A., Gerson, S. C. & Jarvik, L. F. (1987) Antidepressant drug treatment in the elderly. In Psychopharmacology, the Third Generation of Progress: The Emergence of Molecular Biology & Biological Psychiatry (ed. Meltzer, H. Y.), pp. 1149–1158. New York: Raven Press.Google Scholar
Reifler, B. V., Larson, E., Terj, L., et al (1986) Dementia of the Alzheimer's type and depression. Journal of the American Geriatric Society, 34, 855–859.Google Scholar
Rockwell, E., Lam, R. W. & Zisook, S. (1988) Antidepressant drug studies in the elderly. Psychiatric Clinics of North America, 11, 215–233.Google Scholar
Salzman, C., Shader, R. I. & Pearlman, M (1970) In Psychotropic Drug Side Effects (eds. Shader, R. I. & DiMascio, A.), pp. 261–279. Baltimore: Williams & Wilkins.Google Scholar
Saunders, P. A., Copeland, J. R., Dewey, M. E., et al (1993) The prevalence of dementia, depression and neurosis in later life: The Liverpool MRC-ALPHA Study. International Journal of Epidemiology, 22, 838–847.Google Scholar
Schifano, F., Garbin, A., Renesto, V., et al (1990) A double-blind comparison of mianserin and maprotiline in depressed medically ill elderly people. Acta Psychiatrica Scandinavica, 81, 289–294.Google Scholar
Schoerlin, M-P., Da Prada, M. (1990) Species-specific biotransformation of moclobemide: a comparative study in rats and humans. Acta Psychiatrica Scandinavica, (suppl. 360), 108–110.Google Scholar
Shader, R. I., Harmatz, J. S. & Salzman, C. (1974) A new scale for assessment in geriatric populations: Sandoz Clinical Assessment-Geriatric (SCAG). Journal of American Geriatric Society, 22, 107–113.CrossRefGoogle ScholarPubMed
Small, G. W. (1988) Psychopharmacological treatment of elderly demented patients. Journal of Clinical Psychiatry, 49 (suppl.), 8–13.Google Scholar
Tollefson, G. D., Bosomworth, J. C., Heiugenstein, J. H., et al (1995) A double-blind, placebo-controlled clinical trial of fluoxetine in geriatric patients with major depression. International Psychogeriatrics, 7, 89–104.Google Scholar
Versiani, M., Oggbro, U., Alterwain, P., et al (1989) A double-blind comparative trial of moclobemide v. imipramine and placebo in major depressive episodes. British Journal of Psychiatry, 155 (suppl. 6), 72–77.Google Scholar
Volz, H. P. & Moller, H. J. (1994) Antidepressant drug therapy in the elderly – A critical review of the controlled clinical trials conducted since 1980. Pharmacopsychiatry, 27, 93–100.Google Scholar
Wragg, R. E. & Jeste, D. V. (1989) Overview of depression and psychosis in Alzheimer's disease. American Journal of Psychiatry, 146, 577–587.Google Scholar
Yesavage, J. A., Brink, T. L., Rose, T. L., et al (1983) Development and validation of geriatric depression screening scale: A preliminary report. Journal of Psychiatric Research, 17, 37–49.Google Scholar
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