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Pharmacological management of treatment-resistant depression

Published online by Cambridge University Press:  02 January 2018

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The management of patients with depression who have failed to respond to antidepressant medication is a common problem in general and old age psychiatry. It has been estimated that about 20–30% of patients with major depression fail to respond to treatment with a single antidepressant drug given in adequate dosage for an appropriate period of time. At the current time there are many possible ways to pursue pharmacological treatment, but few controlled trials to help us choose between the various options. In addition there are few clinical predictors to help match patients to an appropriate treatment.

Research Article
Copyright © The Royal College of Psychiatrists 1998 


American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised)(DSM–III–R). Washington, DC: APA.Google ScholarPubMed
Anderson, I. (1997) Lessons to be learnt from meta-analyses of newer versus older antidepressants. Advances in Psychiatric Treatment, 3, 5863.CrossRefGoogle Scholar
Artigas, F., Perez, V. & Alvarez, E. (1994) Pindolol induces a rapid improvement of depressed patients treated with serotonin reuptake inhibitors. Archives of General Psychiatry, 51, 248251.CrossRefGoogle ScholarPubMed
Barker, W. A., Scott, J. & Eccelston, D. (1987) The Newcastle Chronic Depression Study: results of a treatment regime. International Clinical Psychopharmacology, 2, 261272.CrossRefGoogle ScholarPubMed
Blier, P. & de Montigny, C. (1994) Current advances and trends in the treatment of depression. Trends in Pharmacological Sciences, 15, 220226.CrossRefGoogle ScholarPubMed
Blier, P. & Bergeron, R. (1995) Effectiveness of pindolol with selective antidepressant drugs in the treatment of major depression. Journal of Clinical Psychopharmacology, 15, 217222.CrossRefGoogle ScholarPubMed
Chalmers, J. S. & Cowen, P. J. (1990) Drug treatment of tricyclic resistant depression. International Review of Psychiatry, 2, 239248.CrossRefGoogle Scholar
Cowen, P. J. (1998) Treatments for resistant depression. In The Management of Depression (ed. Checkley, S.) pp. 234251. London: Blackwell.Google Scholar
Fava, M., Rosenbaum, J. F., McGrath, P. J. et al (1994) Lithium and tricyclic augmentation of fluoxetine treatment for major depression: a double-blind controlled study. American Journal of Psychiatry, 151, 13721374.Google ScholarPubMed
Hamilton, M. (1967) Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology, 6, 278296.CrossRefGoogle ScholarPubMed
Hale, A. S., Procter, A. W. & Bridges, P. K. (1987) Clomipramine, tryptophan and lithium in combination for resistant endogenous depression: seven case studies. British Journal of Psychiatry, 151, 213217.CrossRefGoogle ScholarPubMed
Himmelhoch, J. M., Thase, M. E., Mailinger, A. G. et al (1991) Tranylcypromine versus imipramine in anergic bipolar depression. American Journal of Psychiatry, 148, 910916.Google ScholarPubMed
Holmes, J. (1995) Supportive psychotherapy. The search for positive meanings. British Journal of Psychiatry, 167, 439455.CrossRefGoogle ScholarPubMed
Hurowitz, G. I. & Liebowitz, M. R. (1993) Antidepressant-induced rapid cycling: six case reports. Journal of Clinical Psychopharmacology, 13, 5256.CrossRefGoogle ScholarPubMed
Joffe, R. T., Singer, W., Levitt, A. J. et al (1993) A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression. Archives of General Psychiatry, 50, 387393.CrossRefGoogle ScholarPubMed
Johnson, F. N. (1991) Lithium augmentation therapy for depression. Reviews in Contemporary Pharmacotherapy, 2, 352.Google Scholar
Katona, C. L. E., Abou-Saleh, M. T., Harrison, D. A. et al (1995) Placebo-controlled trial of lithium augmentation of fluoxetine and lofepramine. British Journal of Psychiatry, 166, 8086.CrossRefGoogle ScholarPubMed
Kupfer, D. J. & Frank, E. (1996) Maintenance therapy for chronic depression. Archives General Psychiatry, 53, 775776.CrossRefGoogle Scholar
Lindberg, G., Bingefors, K., Ranstam, J. et al (1998) Use of calcium channel blockers and risk of suicide: ecological findings confirmed in population based cohort study. British Medical Journal, 316, 741745.CrossRefGoogle ScholarPubMed
Moreno, F. A., Gelenberg, A. J., Bachar, K. et al (1997) Pindolol augmentation of treatment-resistant depressed patients. Journal of Clinical Psychiatry, 58, 437439.CrossRefGoogle ScholarPubMed
Mueller, T. J., Keller, M. B., Leon, A. C. et al (1996) Recovery after 5 years of unremitting major depressive disorder. Archives General Psychiatry, 53, 794799.CrossRefGoogle ScholarPubMed
Muller-Siecheneder, F., Muller, M. J., Hillert, A. et al (1998) Risperidone versus haloperidol and amitriptyline in the treatment of patients with a combined psychotic and depressive syndrome. Journal of Clinical Psychopharmacology, 18, 111120.CrossRefGoogle ScholarPubMed
Nierenberg, A. A. & Keck, P. E. (1989) Management of monoamine oxidase inhibitor-associated insomnia with trazodone. Journal of Clinical Psychopharmacology, 9, 4554.CrossRefGoogle ScholarPubMed
Nolen, W. A., Van de Putte, J. J., Dijken, W. A. et al (1988) Treatment strategy in depression. II. MAO inhibitors in depression resistant tricyclic antidepressants: two controlled cross-over studies with tranylcypromine versus 1–5-hydroxytryptophan and nomifensine. Acta Psychiatrica Scandinavica, 78, 676683.CrossRefGoogle Scholar
Preskorn, S. H. (1993) Pharmacokinetics of antidepressants: Why and how are they relevant to treatment? Journal of Clinical Psychiatry, 54 (suppl. 9), 1434.Google Scholar
Price, L. H., Charney, D. S. & Heninger, G. R. (1985) Efficacy of lithium-tranylcypromine treatment in refractory depression. American Journal of Psychiatry, 142, 619623.Google ScholarPubMed
Prudic, J., Sackeim, H. A. & Devanand, D. P. (1990) Medication resistance and clinical response to electroconvulsive therapy. Psychiatry Research, 31, 287296.CrossRefGoogle ScholarPubMed
Quitkin, F. M., McGrath, P. J., Stewart, J. W. et al (1989) Phenelzine and imipramine in mood reactive depressives. Archives of General Psychiatry, 46, 787793.Google ScholarPubMed
Rothschild, A. J., Samson, J. A., Bessette, M. P. et al (1993) Efficacy of the combination of fluoxetine and perphenazine in the treatment of psychotic depression. Journal of Clinical Psychiatry, 54, 338342.Google ScholarPubMed
Sackeim, H. A., Prudic, J., Devenand, D. P. el al (1990) The impact of medication resistance and continuation of pharmacotherapy on relapse following response to electroconvulsive therapy in major depression. Journal of Clinical Psychopharmacology, 10, 96104.CrossRefGoogle ScholarPubMed
Seth, R., Jennings, A. L., Bindman, J. et al (1992) Combination treatment with noradrenaline and serotonin reuptake inhibitors in resistant depression. British Journal of Psychiatry, 161, 562565.CrossRefGoogle Scholar
Sethna, E. R. (1974) A study of refractory cases of depressive illnesses and the response to combined antidepressant treatment. British Journal of Psychiatry, 124, 265272.CrossRefGoogle ScholarPubMed
Slutsker, L., Hoesly, F. C., Miller, L. et al (1990) Eosinophiliamyalgia syndrome associated with exposure to tryptophan from a single manufacturer. Journal of the American Medical Association, 264, 213217.CrossRefGoogle Scholar
Spiker, D. G., Weiss, J. C. & Dealy, R. S. (1985) The pharmacological treatment of delusional depression. American Journal of Psychiatry, 142, 430436.Google ScholarPubMed
Stabl, M., Kasas, A., Blajev, B. et al (1995) A double-blind comparison of moclobemide and thioridazine versus moclobemide and placebo in the treatment of refractory severe depression. Journal of Clinical Psychopharmacology, 15 (suppl. 2), 41S45S.CrossRefGoogle ScholarPubMed
Sternbach, H. (1991) The serotonin syndrome. American Journal of Psychiatry, 148, 705713.Google ScholarPubMed
Taylor, D. (1995) Selective serotonin reuptake inhibitors and tricyclic antidepressants in combination: interactions and therapeutic uses. British Journal of Psychiatry, 167, 575580.CrossRefGoogle ScholarPubMed
Thase, M. E. & Rush, A. J. (1997) When at first you don't succeed: sequential strategies for antidepressant non-responders. Journal of Clinical Psychiatry, 58 (suppl. 13), 2329.Google Scholar
Tyrer, P. & Murphy, S. (1990) Efficacy of combined antidepressant therapy in resistant neurotic disorder. British Journal of Psychiatry, 156, 115118.CrossRefGoogle ScholarPubMed
Weilburg, J. B., Rosenbaum, J. F., Biderman, J. et al (1989) Fluoxetine added to non-MAOI antidepressants converts non-responders to responders: a preliminary report. Journal of Clinical Psychiatry, 50, 447449.Google Scholar
Weilburg, J. B., Rosenbaum, J. F., Meltzer-Brody, S. et al (1991) Tricyclic augmentation of fluoxetine. Annals of Clinical Psychiatry, 3, 209213.CrossRefGoogle Scholar
Young, A. H. & Cowen, P. J. (1994) Antidepressant drugs. In Side-Effects of Drugs Annual, Vol. 17 (eds Aronson, J. K. & Van Boxtel, C. J.) pp. 1625. Amsterdam: Elsevier.Google Scholar
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