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Placebo-Controlled Trial of Lithium Augmentation of Fluoxetine and Lofepramine

Published online by Cambridge University Press:  02 January 2018

Cornelius L. E. Katona ,
Mohammed T. Abou-Saleh ,
Deborah A. Harrison ,
Bertrand A. Nairac ,
Denzil R. L. Edwards ,
Toni Lock ,
Robert A. Burns  and
Mary M. Robertson
Cornelius L. E. Katona*
Affiliation:
Department of Psychiatry, University College London Medical School
Mohammed T. Abou-Saleh
Affiliation:
Department of Psychiatry, Royal Liverpool Hospital
Deborah A. Harrison
Affiliation:
Lilly Industries Ltd, Dextra Court, Chapel Hill, Basingstoke, Hampshire RG 21 2SY
Bertrand A. Nairac
Affiliation:
Department of Psychiatry, University College London Medical School
Denzil R. L. Edwards
Affiliation:
Department of Psychiatry, University College London Medical School
Toni Lock
Affiliation:
Department of Psychiatry, Royal Liverpool Hospital
Robert A. Burns
Affiliation:
Department of Psychiatry, Royal Liverpool Hospital
Mary M. Robertson
Affiliation:
Department of Psychiatry, University College London Medical School
*
Professor Cornelius L. E. Katona, Department of Psychiatry, University College London Medical School, Wolfson Building, Middlesex Hospital, London W1N 8AA
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Abstract

Background

This study was designed to establish whether (as suggested in a number of open and relatively small controlled trials) lithium augmentation is more effective than continued antidepressant alone, where response to a standard course of antidepressant treatment has been absent or partial.

Method

Lithium or placebo was added on a double-blind basis for six weeks to the drug regime of 62 patients with major depressive illness (in both hospital and primary care settings) who had failed to respond to a controlled trial of fluoxetine or lofepramine. Response was defined as a final Hamilton Depression Rating Scale (HDRS) score of < 10.

Results

Response was seen more frequently in patients taking lithium (15/29) than in those remaining on antidepressant alone (8/32; P < 0.05). Rapid response to lithium augmentation (LA) was not consistently observed in this cohort. Mean HDRS scores after six weeks were significantly lower (P < 0.01) in the lithium group after excluding those who had not achieved significant exposure to lithium (arbitrarily defined as two or more lithium levels ≥ 0.4 mmol/1). No differences in the efficacy of LA were apparent between fluoxetine and lofepramine.

Conclusions

Our results confirm that LA is a useful strategy in the treatment of antidepressant-resistant depression. Partial response was, however, frequently observed with continued antidepressant treatment alone, and the superiority of LA appears to depend on achieving adequate serum lithium levels.

Type
Papers
Information
The British Journal of Psychiatry , Volume 166 , Issue 1 , January 1995 , pp. 80 - 86
Copyright
Copyright © 1995 The Royal College of Psychiatrists 

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References

American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM–III–R). Washington, DC: APA.Google Scholar
Austin, M. P. V., Souza, F. G. M. & Goodwin, G. M. (1991) Lithium augmentation in antidepressant-resistant patients. A quantitative analysis. British Journal of Psychiatry, 159, 510–514.CrossRefGoogle ScholarPubMed
Carney, M. W. P., Roth, M. & Garside, R. F. (1965) The diagnosis of depressive syndromes and the prediction of ECT response. British Journal of Psychiatry, 11, 659–674.CrossRefGoogle Scholar
Committee on Safety of Medicines (1989) Current Problems No. 26. London: CSM.Google Scholar
de Montigny, C., Grunberg, F., Mayer, A., et al (1981) Lithium induces rapid relief of depression in tricyclic antidepressant drug non-responders. British Journal of Psychiatry, 138, 252–256.Google Scholar
Georgotas, A., McCue, R. E., Cooper, G. L., et al (1989) Factors affecting the delay of antidepressant effect in responders to nortriptyline and phenelzine. Psychiatry Research, 28, 1–9.CrossRefGoogle ScholarPubMed
Greenhouse, J. B., Kupfer, D. J., Frank, E., et al (1987) Analysis of time to stabilisation in the treatment of depression: biological and clinical correlates. Journal of Affective Disorders, 13, 259–266.Google Scholar
Hamilton, M. (1967) Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology, 6, 278–296.CrossRefGoogle ScholarPubMed
Jefferson, J. W., Greist, J. H., Ackerman, D. L., et al (1987) Dose, low level therapy. In Lithium Encyclopedia for Clinical Practice (2nd edn) (eds Jefferson, J. W., Greist, J. H., Ackerman, D. L., et al), pp. 254–259. Washington, DC: American Psychiatric Press.Google Scholar
Katona, C. L. E. (1988) Lithium augmentation in refractory depression. Psychiatric Developments, 2, 153–171.Google Scholar
Keller, M. B., Klerman, G. L., Lavori, P. W., et al (1984) Long-term outcome of episodes of major depression. Journal of the American Medical Association, 252, 788–792.Google Scholar
Klein, D. F. & Davis, J. M. (1969) Diagnosis and Drug Treatment of Psychiatric Disorder. Baltimore: Williams and Wilkins.Google Scholar
Leonard, B. E. (1987) A comparison of the pharmacological properties of the novel tricyclic antidepressant lofepramine with its major metabolite desipramine: a review. International Clinical Psychopharmacology, 2, 281–297.CrossRefGoogle ScholarPubMed
Montgomery, S. A. & Asberg, M. (1979) A new depression scale designed to be sensitive to change. British Journal of Psychiatry, 134, 382–389.Google Scholar
Muijen, M., Roy, D., Silverstone, T., et al (1988) A comparative trial of fluoxetine, mianserin and placebo with depressed outpatients. Acta Psychiatrica Scandinavica, 78, 384–390.Google Scholar
Price, L. H., Charney, D. S. & Heninger, G. R. (1986) Variability of response to lithium augmentation in refractory depression. American Journal of Psychiatry, 143, 1387–1392.Google Scholar
Robertson, M. M., Abou-Saleh, M. T., Harrison, D. A., et al (1994) A double-blind controlled comparison of fluoxetine and lofepramine in major depressive illness. Journal of Psychopharmacology, 8, 98–103.CrossRefGoogle ScholarPubMed
Stein, G. & Bernadt, M. (1993) Double blind trial of lithium augmentation therapy in tricyclic-resistant depression. A controlled trial using lithium in low and normal doses. British Journal of Psychiatry, 162, 634–640.CrossRefGoogle ScholarPubMed
Welkowitz, J., Ewen, R. B. & Cohen, J. (1982) Introductory Statistics for the Behavioural Sciences (3rd edn). London: Academic Press.Google Scholar
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