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The treatment of depression in general practice: a comparison of L-tryptophan, amitriptyline, and a combination of L-tryptophan and amitriptyline with placebo

  • Joan Thomson, H. Rankin, G. W. Ashcroft, Celia M. Yates, Judith K. McQueen and S. W. Cummings...

One hundred and fifteen patients from 5 general practices participated in a 12-week, double-blind study comparing L-tryptophan, amitriptyline, L-tryptophan–amitriptyline combination and placebo in the treatment of depression. Analysis of total score on the Hamilton Depression Scale and a global rating of depression showed that all 3 active treatments were more effective than placebo. Significantly more patients were withdrawn as treatment failures in the placebo group compared with the active treatment groups. Side-effects necessitated withdrawal of more patients from the amitriptyline group than from the other active tratment groups, but this difference was not significant. Plasma amitriptyline and nortriptyline levels were similar in the difference was not significant. Plasma amitriptyline and nortriptyline and biochemical profiles did not alter significantly in any group, but mean heart rate was significantly increased in patients receiving amitriptyline. There was no change in free or total plasma tryptophan concentration with treatment or on remission of symptoms.

Corresponding author
1Address for correspondence: Dr Joan Thomson, Bangour Village Hospital, Dechmont, west Lothian EH52 6LW
2Stockbridge Health Centre, I India Place, Edinburgh
3Department of Mental Health, University Medical Buildings, Foresterhill, Aberdeen
4MRC Brain Metabolism Unit, George Square, Edinburgh
5Berk Pharmaceuticals Ltd, St Leonards House, St Leonards Road, Eastbourne, Sussex
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Aylward, M. (1973). Plasma tryptophan levels and mental depression in postmenopausal subjects: effects of oral piperazine oestrone sulphate. International Research Communications System 1, 30.
Bartlett, J. R., Bridges, P. K., Curzon, G., Gillman, P. K., Hunt, A., Kantamaneni, B. D. & Patel, J. (1981). Effect of tryptophan infusion on plasma, CSF, and brain tryptophan in man. British Journal of Clinical Pharmacology 12 (2), 277278.
Blashki, T. G., Mowbray, R. & Davies, B. (1971). Controlled trial of amitriptyline in general practice. British Medical Journal i, 133138.
Braithwaite, R. A. & Widdop, B. (1971). A specific gas-chromatographic method for the measurement of steady-state plasma levels of amitriptyline and nortriptyline in patients. Clinica chemica acta 35, 461472.
Braithwaite, R. A., Goulding, R. & Thean, G. et al. (1972). Plasma concentration of amitriptyline and clinical response. Lancet i, 12971300.
Bunney, W. E. Jr, Brodie, H. K. H., Murphy, D. L. & Goodwin, F. K. (1971). Studies of alpha-methyl-para-tyrosine, L-dopa, and L-tryptophan in depression and mania. American Journal of Psychiatry 127, 872881.
Carroll, B. J., Mowbray, R. M. & Davis, B. (1970). Sequential comparison of L-tryptophan with ECT in severe depression. Lancet i, 967969.
Chouinard, G., Young, S. N., Annable, L. & Sourkes, T. L. (1979). Tryptophan-nicotinamide, imipramine and their combination in depression. A controlled study. Acta psychiatrica scandanavica 59, 395414.
Coppen, A., Shaw, D. M., Herzberg, B. & Maggs, R. (1967). Tryptophan in the treatment of depression. Lancet ii, 11781180.
Coppen, A., Whybrow, P. C., Noguera, R., Maggs, R. & Prange, A. J. (1972). The comparative antidepressant value of L-tryptophan and imipramine with and without attempted potentiation by liothyro-nine. Archives of General Psychiatry 26, 234241.
Coppen, A., Eccleston, E. G. & Peet, M. (1973). Total and free tryptophan concentration in plasma of depressive patients. Lancet ii, 6063.
Coppen, A., Ghose, K. & Montgomery, S. et al. (1978). Amitriptyline plasma concentration and clinical effect. Lancet i, 6366.
Curzon, G. (1979). Relationships between plasma, CSF, and brain tryptophan. Journal of Neural Transmission Suppl. 15, 8192.
Duncan, D. B. (1955). Multiple range and multiple Ftests. Biometrics 03, 142.
Dunner, D. L. & Fieve, R. R. (1975). Affective disorder: studies with amine precursors. American Journal of Psychiatry 132, 180183.
Green, A. R., Aronson, J. K., Curzon, G. & Woods, H. F. (1980). Metabolism of an oral tryptophan load. I. Effects of dose and pre-treatment with tryptophan. British Journal of Clinical Pharmacology 10, 603610.
Hamilton, M. (1960). A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 23, 5662.
Herrington, R. N., Bruce, A., Johnstone, E. C. & Lader, M. H. (1974). Comparative trial of L-tryptophan and ECT in severe depressive illness. Lancet ii, 731734.
Herrington, R. N., Bruce, A., Johnstone, E. C. & Lader, M. H. (1976). Comparative trial of L-tryptophan and amitriptyline in depressive illness. Psychological Medicine 6, 673678.
Hess, S. M. & Udenfriend, S. (1959). A fluorimetric procedure for the estimation of tryptamine in tissues. Journal of Pharmacology and Experimental Therapeutics 127, 175177.
Jensen, K., Fruensgaard, K. & Ahlfors, U.-G. et al. (1975). Tryptophan/imipramine in depression. Lancet ii, 920.
Johnson, D. A. W. (1973). Treatment of depression in general practice. British Medical Journal ii, 1820.
Kupfer, D. J., Hanin, I. & Spiker, D. (1978). Amitriptyline plasma levels and clinical response in primary depression. Communications in Psychopharmacology 2, 441450.
Lopez-Ibor, Alino J. J., Ayuso Gutierrez, J. L. & Montejo Iglesias, M. L. (1973). Tryptophan and amitriptyline in the treatment of depression. A double blind study. International Pharmacopsychiatry 8, 145151.
McNenamy, R. H. & Oncley, J. L. (1958). The specific binding of L-tryptophan to serum albumin. Journal of Biological Chemistry 233, 14361447.
Mantel, N. & Haenszel, W. (1959). Statistical aspects of the analysis of data from retrospective studies of disease. Journal of the National Cancer Institute 22. 719748.
Mendels, J., Stinnett, J. K.. Burns, D. & Frazer, A. (1975). Amine precursors and depression. Archives of General Psychiatry 32. 2230.
Montgomery, S., McAuley, R., Rani, S. J., Montgomery, D. B., Braithwaite, R. & Dawling, S. (1979). Amitriptyline plasma concentration and clinical response. British Medical Journal i 230231.
Murphy, D. L., Baker, M., Goodwin, F. K.. Miller, J., Kotin, J. & Bunney, W. E. Jr (1974). L-Tryptophan in affective disorders. Indolearnine changes and differential clinical effects. Psychopharmacologia, 34, 1120.
Murphy, J. E., Donald, J. F. & Molla, A. L. (1976). Mianserin in the treatment of depression in general practice. Practitioner 217, 135138.
Niskanen, P., Huttunen, M., Tamminen, T. & Jaaskelainen, J. (1976). The daily rhythm of plasma tryptophan and tyrosine in depression. British Journal of Psychiatry 128. 6773.
Peet, M., Moody, J. P., Worrall, E. P., Walker, P. & Naylor, G. J. (1976). Plasma Iryptophan concentration in depression and mania. British Journal of Psychiatry 128. 255258.
Porter, A. M. W. (1970). Depressive illness in a general practice. A demographic study and a controlled trial of imipramine. British Medical Journal i, 773778.
Rao, B. & Broadhurst, A. D. (1976). Tryptophan and depression. British Medical Journal i, 460.
Rickels, K., Gordon, P. E., Jenkins, B. W., Perloff, M., Sachs, T. & Stepansky, W. (1970). Drug treatment in depressive illness (amitriptyline and chlordiazepoxide in two neurotic populations). Diseases of the Nervous System 31, 3042.
Riley, G. J. & Shaw, D. M. (1976). Total and non-bound tryptophan in unipolar illness. Lancet ii, 1249.
S.A.S. User's Guide (1979 edition), S.A.S. Institute Inc.: Cary, North Carolina.
Spitzer, R. L., Endicott, J. & Robins, E. (1977). Research Diagnostic Criteria (RDC) for a Selected Group of Functional Disorders (3rd edn). New York State Psychiatric Institute: New York.
Wålinder, J., Skott, A., Carlsson, A., Nagy, A. & Roos, B.-E. (1976). Potentiation of the antidepressant action of clomipramine by tryptophan. Archives of General Psychiatry 33, 13841389.
Wing, J. K., Cooper, J. E. & Sartorius, N. (1974). Measurement and Classification of Psychiatric Symptoms. Cambridge University Press: Cambridge.
Ziegler, V. E., Cox, B. T. & Taylor, J. R. (1976). Amitriptyline plasma levels and therapeutic response. Clinical Pharmacology and Therapeutics 19, 795801.
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Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
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