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A Study of the Effects of Desipramine Treatment Alone and in Combination with L-Triiodothyronine on 6-Sulphatoxymelatonin Excretion in Depressed Patients

Published online by Cambridge University Press:  02 January 2018

J. Bearn*
Affiliation:
Institute of Psychiatry
J. Arendt
Affiliation:
Department of Biochemistry, University of Surrey
S. A. Checkley
Affiliation:
Maudsley Hospital, London
*
Institute of Psychiatry, De Crespigny Park, London SE5 8AF

Abstract

Urinary 6-sulphatoxymelatonin (αMT6s) excretion was measured after one day and one, two and three weeks of desipramine treatment in eight depressed patients. There was a significant increase in the urinary excretion of αMT6s after one week of treatment, and at no time was there any decrease in αMT6s excretion. These findings are opposed to the hypothesis that desipramine reduces noradrenergic neurotransmission in the human pineal. In a further five patients whose depression was resistant to desipramine alone, urinary αMT6s excretion was measured during treatment with adjunctive L-triiodothyronine (T3). There was no change in αMT6s excretion, and thus the previously reported potentiation of the efficacy of tricyclic antidepressants in combination with T3 does not appear to be mediated through an alteration in noradrenergic neurotransmission.

Type
Papers
Copyright
Copyright © Royal College of Psychiatrists, 1989 

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References

Arendt, J., Bojkowski, C., Franey, C., et al (1985) Immunoassay of 6-hydroxymelatonin sulphate in human plasma and urine: abolition of the urinary 24-hour rhythm with atenolol. Journal of Clinical Endocrinology and Metabolism, 60, 11661173.Google Scholar
Bojkowski, C., Arendt, J., Shih, M., et al (1987) Melatonin secretion in humans assessed by measuring its metabolite: 6-sulfatoxymelatonin. Clinical Chemistry, 33, 13431348.Google Scholar
Brochet, D. M., Martin, P., Soubrie, P., et al (1987) Triiodothyronine potentiation of antidepressant-induced reversal of learned helplessness in rats. Psychiatry Research 21, 267275.Google Scholar
Brown, R. P., Caroff, S., Kocsis, J. H., et al (1985) Nocturnal serum melatonin in major depressive disorder before and after desmethylimipramine treatment. Psychopharmacology Bulletin, 21, 579581.Google Scholar
Burns, T. G. & Brown, G. M. (1984) The effects of acute and chronic desmethylimipramine treatment on pineal and serum melatonin and N-acetylserotonin. Advances in the Biosciences, 53, 2530.Google Scholar
Checkley, S. A., Corn, T. H., Glass, I. B., et al (1986) Neuroendocrine and other studies of the mechanism of antidepressant action of desipramine In Antidepressants and Receptor Function (CIBA Foundation Symposium 123), pp. 126147. Chichester: Wiley.Google Scholar
Coppen, A., Whybrow, P. C., Noguera, R., et al (1972) The comparative antidepressant value of L-tryptophan and imipramine with and without attempted potentiation by Liothyronine. Archives of General Psychiatry, 26, 234241.Google Scholar
Cowen, P. J., Fraser, S., Grahame-Smith, D. G., et al (1983) The effect of chronic antidepressant administration on beta-adrenoceptor function of the rat pineal. British Journal of Pharmacology, 78, 8996.Google Scholar
Cowen, P. J., Green, A. R., Grahame-Smith, D. G., et al (1985) Plasma melatonin during desmethylimipramine treatment: evidence for changes in noradrenergic transmission. British Journal of Clinical Pharmacology, 19, 799805.Google Scholar
Eriksson, E., Eden, S. & Modigh, K. (1982) Up and down-regulation of central post-synaptic alpha, adrenoceptors reflected in the GH response to clonidine in reserpine pretreated rats. Psychopharmacology, 77, 327331.CrossRefGoogle Scholar
Feighner, J. P., King, L. J., Schuckit, M. A., et al (1972) Hormonal potentiation of imipramine and ECT in primary depression. American Journal of Psychiatry, 128, 12301238.Google Scholar
Frazer, A., Brown, R., Kocsis, J., et al (1986) Patterns of melatonin rhythms in depression. Journal of Neural Transmission (suppl.) 21, 269290.Google Scholar
Friedman, E., Yocca, F. D. & Cooper, T. B. (1984) Antidepressant drugs with varying pharmacological profiles alter rat pineal beta adrenergic mediated function. Journal of Pharmacology and Experimental Therapeutics, 228, 545549.Google Scholar
Gitlin, M. J., Weiner, H., Fairbanks, L., et al (1987) Failure of T3 to potentiate tricyclic antidepressant response. Journal of Affective Disorders, 13, 267272.Google Scholar
Golden, R. N., Markey, S. P., Risby, E. D., et al (1988) Antidepressants reduce whole body norepinephrine turnover while enhancing 6-hydroxymelatonin output. Archives of General Psychiatry, 45, 150154.CrossRefGoogle ScholarPubMed
Goodwin, F. K., Pranoe, A. J., Post, R. M., et al (1982) Potentiation of antidepressant effects by L-triiodothyronine in tricyclic nonresponders. American Journal of Psychiatry, 139, 3438.Google Scholar
Hamilton, M. (1967) Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychiatry, 6, 278296.CrossRefGoogle ScholarPubMed
Heal, D. J., Lister, S., Smith, S. L., et al (1983) The effects of acute and repeated administration of various antidepressant drugs on clonidine-induced hypoactivity in the rat. Neuropharmacology, 22, 983992.Google Scholar
Heal, D. J., Bristow, L. J., Elliot, J. M., et al (1987) The influence of L-triiodothyronine (T3) on the effects of repeated administration of desipramine or electroconvulsive shock on alpha2- and beta-adrenoceptor function in the brain of the rat: implications for the potentiation of antidepressant therapy by T3 . Neuropharmacology, 26, 11311139.Google Scholar
Heydorn, W. E., Brunswick, D. J. & Frazer, A. (1982) Effect of treatment of rats with antidepressants on melatonin concentrations in the pineal gland and serum. Journal of Pharmacology and Experimental Therapeutics, 222, 534543.Google Scholar
Joffe, R. T., Post, R. M., Sulser, F., et al (1988) Effects of thyroid alterations and carbamazepine on cortical beta-adrenergic receptors in the rat. Neuropharmacology, 27, 171174.Google Scholar
Lewy, A. J. (1984) Human melatonin secretion: a marker for adrenergic function In Neurobiology of Mood Disorders (eds R. V. Post & J. C. Ballenger), pp. 207214. Baltimore: William and Wilkins.Google Scholar
Mason, G. A., Bondy, S. C., Nemeroff, C. B., et al (1987) The effects of thyroid state on beta-adrenergic and serotonergic receptors in rat brain. Psychoneuroendocrinology, 12, 261270.CrossRefGoogle ScholarPubMed
McIntyre, I. M., Burrows, G. D. & Norman, T. R. (1988) Suppression of plasma melatonin by a single dose of the benzodiazepine alprazolam in humans. Biological Psychiatry, 24, 105108.Google Scholar
Mendlewicz, J., Branchey, L., Weinberg, U., et al (1980) The 24 hour pattern of plasma melatonin in depressed patients before and after treatment. Communications of Psychopharmacology, 4, 4955.Google Scholar
Menkes, D. B., Aghajanian, G. K. & Gallagher, D. W. (1983) Chronic antidepressant treatment enhances agonist affinity of brain alpha, adrenoceptors. European Journal of Pharmacology, 87, 3541.Google Scholar
Pelayo, F., Dubocovich, M. L. & Langer, S. Z. (1977) Regulation of noradrenaline release in the rat pineal through a negative feedback mechanism mediated by presynaptic alpha adrenoceptors. European Journal of Pharmacology, 45, 317318.Google Scholar
Plaznik, A., Danysz, W. & Kostowski, W. (1984) Behavioural evidence for alpha, adrenoceptor up- and alpha2 adrenoceptor down- regulation in the rat hippocampus after chronic desipramine treatment. European Journal of Pharmacology, 101, 305306.CrossRefGoogle Scholar
Prange, A. J., Wilson, I. C., Rabon, A. M., et al (1969) Enhancement of imipramine antidepressant activity by thyroid hormone. American Journal of Psychiatry, 126, 3950.Google Scholar
Sack, R. L. & Lewy, A. J. (1986) Desmethylimipramine treatment increases melatonin production in humans. Biological Psychiatry, 21, 406410.Google Scholar
Schwartz, G., Halaris, A., Baxter, L., et al (1984) Normal thyroid function in desipramine nonresponders converted to responders by the addition of L-triiodothyronine. American Journal of Psychiatry, 141, 16141616.Google Scholar
Spitzer, R. L., Endicott, J. & Robins, E. (1978) Research Diagnostic Criteria: rationale and reliability. Archives of General Psychiatry, 35, 773782.Google Scholar
Sulser, F. (1984) Regulation and function of noradrenaline receptor systems in brain: psychopharmacological aspects. Neuropharmacology, 23, 255261.CrossRefGoogle ScholarPubMed
Sulser, F., Vetulani, J. & Mobley, P. L. (1978) Mode of action of antidepressant drugs. Biochemical Pharmacology, 27, 257261.Google Scholar
Thompson, C., Mezey, G., Corn, T. H., et al (1985) The effect of desipramine upon melatonin and cortisol secretion in depressed and normal subjects. British Journal of Psychiatry, 147, 389393.Google Scholar
Tsutsui, S., Yamazaki, Y., Namba, T., et al (1979) Combined therapy of T, and antidepressants in depression. Journal of International Medical Research, 7, 138146.Google Scholar
Vanecek, J., Sugden, D., Weller, J., et al (1985) Atypical synergistic alpha, and beta adrenergic regulation of cyclic AMP and cyclic GMP in rat pinealocytes. Endocrinology, 116, 21672173.Google Scholar
Wheatley, D. (1972) Potentiation of amitriptyline by thyroid hormone. Archives of General Psychiatry, 26, 229233.Google Scholar
Zatz, M., Kebabian, J. W., Romero, J. A., et al (1976) Pineal beta adrenergic receptor: correlation of binding of 3H-1-aprenolol with stimulation of adenylate cyclase. Journal of Pharmacology and Experimental Therapeutics, 196, 714722.Google Scholar
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