Hostname: page-component-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-11-25T10:16:01.336Z Has data issue: false hasContentIssue false

Biochemical Aspects of Therapy-Resistant Depression

Published online by Cambridge University Press:  02 January 2018

B. E. Leonard*
Affiliation:
University College, Galway, Republic of Ireland

Abstract

Despite the relatively high incidence of therapy-resistant depression, there is little clinical evidence to suggest that there are significant biochemical differences between therapy-resistant and therapy-responsive patients. A major problem for investigators is the lack of an internationally recognised definition of resistant depression. Also, it is possible that depressed patients with delusional symptoms or rapidly cycling affective disorders form subgroups that are more likely to be resistant to tricylic antidepressant treatment and are therefore classified as therapy-resistant. Evidence is presented to show that an abnormality in serotonergic function may characterise some therapy-resistant depressed patients.

Type
Annotation
Copyright
Copyright © Royal College of Psychiatrists, 1988 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Akiskal, H. S. (1983) Diagnosis and classification of affective disorders: new insights from clinical and laboratory approaches. Psychiatric Developments, 1, 123160.Google ScholarPubMed
Akiskal, H. S. (1985) A proposed approach to chronic and “resistant” depressions: evaluation and treatment. Journal of Clinical Psychiatry, 46, 3236.Google Scholar
Alarcon, R. D. (1985) Rapid cycling affective disorders: a clinical review. Comprehensive Psychiatry, 26, 522540.Google Scholar
Ashcroft, G. W., Crawford, J. B. B., Eccleston, D., Sharman, D., MacDougall, E. J., Stanton, J. B. & Binns, J. (1966) 5-Hydroxyindole compounds in the cerebro-spinal fluid of patients with psychiatric or neurological diseases. The Lancet, ii, 10491052.Google Scholar
Baastrup, C. P. & Schou, M. (1967) Lithium as a prophylactic agent. Archives of General Psychiatry, 16, 162172.Google Scholar
Bridges, P. K. (1983) Point of view. British Journal of Psychiatry, 142, 676687.Google Scholar
Briley, M. S., Langer, S. Z., Raisman, R., Sechter, D. & Zarifian, E. (1980) Tritiated imipramine binding sites are decreased in platelets of untreated depressed patients. Science, 209, 303305.CrossRefGoogle ScholarPubMed
Carroll, B. J. (1982) The dexamethasone suppression test for melancholia. British Journal of Psychiatry, 140, 292304.Google Scholar
Carroll, B. J., Curtis, G. C. & Mendals, J. (1976) Neuroendocrine regulation in depression. Parts I and II. Archives of General Psychiatry, 33, 10391044, 1051–1057.Google Scholar
Carroll, B. J., Greden, J. F., Feinberg, M., James, N. M., Haskett, R. F., Steiner, M. & Tarika, J. (1980) Neuroendocrine dysfunction in genetic sub-types of primary unipolar depression. Psychiatric Research, 2, 251262.Google Scholar
Cassano, G. B., Maggini, C. & Akiskal, H. (1983) Short-term, sub-chronic and chronic sequelae of affective disorders. The Psychiatric Clinics of North America, 6, 5568.CrossRefGoogle Scholar
Coppen, A., Eccleston, D. G. & Peet, M. (1973) Total and free tryptophan concentrations in the plasma of depressive patients. The Lancet, ii, 6063.CrossRefGoogle Scholar
Coppen, A., Swade, C. & Wood, K. (1978) Platelet 5HT accumulation in depressive illness. Clinical Chimica Acta, 87, 165168.Google Scholar
Coppen, A., Noguera, R., Bailey, J., Burns, B. H., Swani, M. S., Hare, E. H., Gardner, R. & Maggs, R. (1971) Prophylactic lithium in affective disorders. The Lancet, ii, 275279.Google Scholar
Cowdry, R. W., Wehr, T. V. & Zis, A. P. (1982) Thyroid abnormalities associated with rapid cyclic bipolar illness. Archives of General Psychiatry, 40, 414420.Google Scholar
Curzon, G., Kantamaneni, B. D., Lader, M. H. & Greenwood, M. H. (1979) Tryptophan disposition in psychiatric patients before and after stress. Psychological Medicine, 9, 457463.Google Scholar
De Montigny, C. & Aghajanian, G. K. (1978) Tricyclic anti-depressants: long term treatment increases responsivity of rat forebrain neurons to serotonin. Science, 202, 13031306.Google Scholar
De Montigny, C., Grunberg, P., Mayer, A. & Deschennes, J. (1981) Lithium induces a rapid relief of depression in tricyclic antidepressant drug non-responders. British Journal of Psychiatry, 138, 252256.Google Scholar
De Montigny, C., Cournoyer, G., Morissette, R., Langlois, R. & Caille, G. (1983) Lithium carbonate addition in tricyclic antidepressant resistant unipolar depression. Archives of General Psychiatry, 40, 13271334.Google Scholar
Dunner, D. L. & Fieve, R. R. (1974) Clinical factors in lithium prophylaxis failure. Archives of General Psychiatry, 30, 229233.Google Scholar
Eccleston, D. G. (1988) Treatment of resistant depression. International Clinical Psychopharmacology (in press).Google Scholar
Extein, I., Pottash, A. L. C. & Gold, M. S. (1982) Does subclinical hypothyroidism predispose to tricyclic induced rapid mood cycles? Journal of Clinical Psychiatry, 43, 290291.Google Scholar
Gallagher, D. W., Pert, A. & Bunney, W. E. (1978) Haloperidol-induced presynaptic dopamine supersensitivity is blocked by chronic lithium. Nature, 273, 309312.Google Scholar
Gershon, S. (1970) Lithium in mania. Clinical Pharmacology and Therapeutics, 11, 168187.Google Scholar
Glassman, A. K., Kantor, S. J. & Shostak, M. (1975) Depression, delusional and drug response. American Journal of Psychiatry, 132, 716719.Google Scholar
Glassman, A. K., & Platman, S. R. (1969) Potentiation of a monoamine oxidase inhibitor by tryptophan. Journal of Psychiatric Research, 7, 8388.Google Scholar
Goodwin, F. K., Murphy, D. L., Dunner, D. L. & Bunney, W. E. (1972) Lithium response in unipolar versus bipolar depression. American Journal of Psychiatry, 129, 4447.CrossRefGoogle ScholarPubMed
Grahame-Smith, D. G. & Green, A. R. (1974) The role of brain 5-hydroxytryptamine in the hyperactivity produced in rats by lithium and monoamine oxidase inhibition. British Journal of Pharmacology, 52, 1926.Google Scholar
Greden, J. F., De Vinge, J. P., & Albala, A. A. (1982) Serial dexamethasone suppression tests among rapidly cycling bipolar patients. Biological Psychiatry, 17, 455462.Google Scholar
Healy, D., Carney, P. A. & Leonard, B. E. (1983) Monoamine-related markers of depression: changes following treatment. Journal of Psychiatric Research, 17, 251260.Google Scholar
Healy, D., Carney, P. A., O'Halloran, A. & Leonard, B. E. (1985) Peripheral adrenoceptors and serotonin receptors in depression. Journal of Affective Disorders, 9, 285296.Google Scholar
Healy, D., O'Halloran, A., Carney, P. A. & Leonard, B. E. (1986a) Platelet 5-HT uptake in delusional and non-delusional depressions. Journal of Affective Disorders, 10, 233239.Google Scholar
Healy, D., O'Halloran, A., Carney, P. A. & Leonard, B. E. (1986b) Variations in platelet 5-hydroxytryptamine in control and depressed populations. Journal of Psychiatry Research, 20, 345353.Google Scholar
Hirschfeld, R. M., Klerman, G. L., Andreasen, N. C., Clayton, P. S. & Keller, M. B. (1986) Psychosocial predictors of chronicity in depressed patients. British Journal of Psychiatry, 148, 648654.Google Scholar
Katona, C. L. E., Theodorou, A. E., Davies, S. L., Yamaguchi, Y., Tunnicliffe, C. A., Hale, A. S., Horton, R. W., Kelly, J. S. & Paykel, E. S. (1986) Platelet binding and neuroendocrine responses in depression. In The Biology of Depression (ed. Deakin, J. F. W.), pp. 121136. London: Gaskell.Google Scholar
Keilholz, P., Terzani, S., Gaspar, M. & Adams, C. (1982) Zur Behandlung therapie resistenter Depressionen: Ergebnisse einer Kombinserten Infusion-therapie. Schweiz Medizinische Wocken schrift, 112, 10901095.Google Scholar
Keller, M. C., Klerman, G. L., Lavorri, P. W., Fawcett, J. A., Coryell, W. & Endicott, J. (1982) Treatment received by depressed patients. Journal of American Medical Association, 248, 18481855.Google Scholar
Knapp, S. & Mandell, A. J. (1975) Effects of lithium chloride on parameters of biosynthetic capacity for 5-hydroxytryptamine in rat brain. Journal of Pharmacology and Experimental Therapeutics, 193, 812823.Google Scholar
Langer, S. Z. & Raisman, R. (1983) Binding of 3H-imipramine and 3H-desipramine as biochemical tools for studies in depression. Neuropharmacology, 22, 407413.Google Scholar
Lingjaerde, O., Edlund, A. H., Gormsen, C. A., Gottfries, C. G., Haugstad, A., Hermann, I. L., Hollnagel, P., Makimattila, A., Rasmussen, K. E., Remuig, J. & Robak, O. H. (1974) The effect of lithium carbonate in combination with tricyclic antidepressants in endogenous depression. Acta Psychiatrica Scandinavica, 50, 233242.Google Scholar
Mellerup, E., Plenge, P. & Rosenberg, R. (1982) 3H-imipramine binding sites in platelets from psychiatric patients. Psychiatric Research, 7, 221227.Google Scholar
Meltzer, H. Y., Cho, H. W., Carroll, B. J. & Russo, P. (1976) Serum dopamines-β-hydroxylase activity in the affective psychoses and schizophrenia – decreased activity in unipolar psychotically depressed patients. Archives of General Psychiatry, 33, 585591.Google Scholar
Mendels, J., Secunda, S. K. & Dyson, W. L. (1972) A controlled study of the antidepressant effects of lithium carbonate. Archives of General Psychiatry, 26, 154157.Google Scholar
Menkes, D. B., Aghajanian, G. K. & McCall, R. B. (1980) Chronic antidepressant treatment enhances α-adrenergic and serotonergic responses in the facial nucleus. Life Sciences, 27, 4555.Google Scholar
Montgomery, S. A. (1982) The non-selective effect of selective antidepressants. Advances in Biochemical Psychopharmacology, 31, 4956.Google Scholar
Muscettola, G., Di Lauro, A. & Giannini, C. (1984a) Blood cells as biological trait markers in affective disorders. Journal of Psychiatric Research, 18, 447456.Google Scholar
Muscettola, G., Potter, W. Z. & Pickar, D. (1984b) Urinary 3-methoxy-4 hydroxyphenylglycol and major affective disorders. Archives General Psychiatry, 41, 337342.Google Scholar
Nelson, J. C. & Byck, R. (1982) Rapid response to lithium in phenelzine non-responders. British Journal of Psychiatry, 141, 8586.Google Scholar
Nelson, J. C. & Mazure, C. M. (1986) Lithium augmentation in psychotic depression refractory to combined drug treatment. American Journal of Psychiatry, 143, 363366.Google Scholar
Nelson, J. C., Khan, A. & Orr, W. (1984) Delusional depression: phenomenology, neuroendocrine function and tricyclic antidepressant response. Journal of Affective Disorders, 6, 297306.CrossRefGoogle ScholarPubMed
Paul, S. M. (1986) Serotonin reuptake sites in platelets and human brain: clinical implications. Proceedings of the World Congress in Psychiatry, Regional Meeting, Copenhagen.Google Scholar
Paul, S. M., Rehavi, M., Skolnick, P., Ballenger, J. B. & Goodwin, F. K. (1981) Depressed patients have decreased binding in tritiated imipramine to platelet serotonin “transporter”. Archives of General Psychiatry, 38, 13151317.Google Scholar
Price, J. S. (1978) Chronic depressive illness. British Medical Journal, 2, 12001201.Google Scholar
Quitkin, F., Rifkin, A. & Klein, D. F. (1978) Imipramine response in deluded depressive patients. American Journal of Psychiatry, 135, 806811.Google Scholar
Quitkin, F., (1985) The importance of dosage in prescribing anti-depressants. British Journal of Psychiatry, 147, 593597.Google Scholar
Riley, G. J. & Shaw, O. M. (1976) Total and non-bound tryptophan in unipolar disease. The Lancet, ii, 1249.Google Scholar
Schou, M. (1968) Lithium in psychiatric therapy and prophylaxis. Journal of Psychiatric Research, 6, 6795.Google Scholar
Spiker, D. G., Coble, P., Cofsky, J., Foster, F. G. & Kuppfer, D. J. (1978) EEG sleep and severity of depression. Biological Psychiatry, 13, 485488.Google Scholar
Spiker, D. G., Weiss, J. C., Dealy, R. S., Griffin, S. J., Hanin, I., Neil, J. F., Perel, J. M., Ross, A. J. & Soloff, P. H. (1985) The pharmacological treatment of delusional depression. American Journal of Psychiatry, 142, 430436.Google Scholar
Sweeney, D., Nelson, C., Bower, M., Maas, J. & Heinger, G. (1978) Delusional versus non-delusional depression – neurochemical differences. The Lancet, ii, 100101.Google Scholar
Standish-Barry, H. M. A. S., Bouras, N., Hale, A. S., Bridges, P. K. & Bartlett, J. R. (1986) Ventricular size and CSF transmitters metabolite concentrations in severe endogenous depression. British Journal of Psychiatry, 148, 386392.Google Scholar
Treiser, S. L., Cascio, C. S. & O'Donoghue, T. L. (1981) Lithium increases serotonin release and decreases serotonin receptors in the hippocampus. Science, 213, 15291531.Google Scholar
Tuomisto, J. & Tukianen, E. (1976) Decreased uptake of 5-hydroxytryptamine in blood platelets from depressed patients. Nature, 263, 596598.Google Scholar
Van Praag, H. M. & Korf, J. (1974) Serotonin metabolism in depression: clinical application of the probenecid test. International Pharmacopsychiatry, 9, 3551.Google Scholar
Van Praag, H. M., Van Burg, W., Bos, E. R. & Dols, L. C. W. (1974) 5-Hydroxytryptophan in combination with clomipramine in “therapy-resistant” depressions. Psychopharmacologia, 28, 267269.Google Scholar
Walinder, J., Skott, A., Carlson, A., Nagy, A. & Roos, B. E. (1976) Potentiation of the antidepressant action of clomipramine by tryptophan. Archives of General Psychiatry, 33, 13841389.Google Scholar
Wang, R. Y. & Aghajanian, G. K. (1980) Enhanced sensitivity of amygdaloid neurons to serotonin and norepinephrine after chronic antidepressant treatment. Communications in Psychopharmacology, 4, 8390.Google Scholar
Wehr, J. A. & Goodwin, F. K. (1979) Rapid cycling in manic depressives induced by tricyclic antidepressants. Archives of General Psychiatry, 36, 555559.Google Scholar
Zall, H. (1971) Lithium carbonate and isocarboxazide – an effective drug approach in severe depressions. American Journal of Psychiatry, 127, 14001403.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.