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Randomised controlled trials investigating pharmacological and psychological interventions for treatment-refractory depression: Systematic review

  • Nicola Stimpson (a1), Niruj Agrawal (a2) and Glyn Lewis (a2)

Abstract

Background

About 30% of people with depression do not respond to an antidepressant at the recommended dose and can be described as having treatment-refractory depression.

Aims

To summarise the findings from all randomised controlled trials (RCTs) that have assessed the efficacy of a pharmacological or psychological intervention for treatment-refractory depression.

Method

We used a systematic search strategy to identify RCTs that included adults aged 18–75 years with a diagnosis of unipolar depression that had not responded to a 4-week course of a recommended dose of an antidepressant.

Results

We identified 16 RCTs. None of the included trials assessed the efficacy of psychotherapy. All the trials were too small to detect an important clinical response. We found only two trials on lithium augmentation, which randomised 50 subjects in total.

Conclusions

There is little evidence to guide the management of depression that has not responded to a course of antidepressants. Treatment-refractory depression is an important public health problem and large pragmatic trials are needed to inform clinical practice.

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Copyright

Corresponding author

Professor Glyn Lewis, Division of Psychiatry, University of Bristol, Cotham House, Cotham Hill, Bristol BS6 6JL, UK. E-mail: glyn.lewis@bristol.ac.uk

Footnotes

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Declaration of interest

G.L. has received payment for lectures from a number of pharmaceutical companies.

Footnotes

References

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American Psychiatric Association (1993) Practice guideline for major depressive disorder in adults. American Journal of Psychiatry, 150, 126.
Anderson, I. M., Nutt, D. J. & Deakin, J. F. (2000) Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 1993 British Association for Psychopharmacology guidelines. British Association for Psychopharmacology. Journal of Psychopharmacology, 14, 320.
Antonuccio, D. O., Akins, W. T., Chatham, P. M., et al (1984) An exploratory study: the psychoeducational group treatment of drug-refractory unipolar depression. Journal of Behavioural Therapy and Experimental Psychiatry, 15, 309313.
Aronson, R., Offman, H. J., Joffe, R. T., et al (1996) Triiodothyronine augmentation in the treatment of refractory depression. A meta-analysis. Archives of General Psychiatry, 53, 842848.
Austin, M. P., Souza, F. G. & Goodwin, G. M. (1991) Lithium augmentation in antidepressant-resistant patients. A quantitative analysis. British Journal of Psychiatry, 159, 510514.
Barker, W. A., Scott, J. & Eccleston, D. (1987) The Newcastle chronic depression study: results of a treatment regime. International Clinical Psychopharmacology, 2, 261271.
Bauer, M. & Dopfmer, S. (1999) Lithium augmentation in treatment-resistant depression: meta-analysis of placebo-controlled studies. Journal of Clinical Psychopharmacology, 19, 427434.
Bech, P., Cialdella, P., Haugh, M. C., et al (2000) Meta-analysis of randomised controlled trials of fluoxetine v. placebo and tricyclic antidepressants in the short-term treatment of major depression. British Journal of Psychiatry, 176, 421428.
Begg, C., Cho, M., Eastwood, S., et al (1996) Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA, 276, 637639.
Chaimowitz, G. A., Links, P. S., Padgett, R. W., et al (1991) Treatment-resistant depression: a survey of practice habits of Canadian psychiatrists. Canadian Journal of Psychiatry, 36, 353356.
Chalmers, I. & Altman, D.G. (1995) Systematic Reviews. London: BMJ.
Clifford, E. M., Whale, R., Sharp, T., et al (1999) Effect of penbutolol on neuroendocrine responses to buspirone and mood in SSRI-refractory patients: A preliminary study. Human Psychopharmacology, 14, 273277.
Drago, F., Motta, A. & Grossi, E. (1983) Intravenous maprotiline in severe and resistant primary depression: a double-blind comparison with clomipramine. Journal of International Medical Research, 11, 7884.
Faravelli, C., Albanesi, G. & Sessarego, A. (1988) Viqualine in resistant depression: a double-blind, placebo-controlled trial. Neuropsychobiology, 20, 7881.
Fava, M., Rosenbaum, J. F., McGrath, P. J., et al (1994) Lithium and tricyclic augmentation of fluoxetine treatment for resistant major depression: a doubleblind, controlled study. American Journal of Psychiatry, 151, 13721374.
Gagiano, C. A., Muller, P. G. M., Gourie, J., et al (1993) The therapeutic efficacy of paroxetine: (a) an open study in patients with major depression not responding to antidepressants; (b) a double blind comparison with amitriptyline in depressed outpatients. Acta Psychiatrica Scandinavica, 80, 130131.
Gitlin, M. J., Weiner, H., Fairbanks, L., et al (1987) Failure of T3 to potentiate tricyclic antidepressant response. Journal of Affective Disorders, 13, 267272.
Hamilton, M. (1960) A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry, 23, 5662.
Joffe, R.T. & Singer, W. (1990) A comparison of triiodothyronine and thyroxine in the potentiation of tricyclic antidepressants. Psychiatry Research, 32, 241251
Joffe, R.T. & Singer, , (1992) Thyroid hormone use to enhance the effects of drugs. Clinical Neuropharmacology, 15 (suppl. 1), 389A390A.
Joffe, R.T. & Singer, , 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.
Klaiber, E. L., Broverman, D. M., Vogel, W., et al (1979) Estrogen therapy for severe persistent depressions in women. Archives of General Psychiatry, 36, 550554.
LeLorier, J., Gregoire, G., Benhaddad, A., et al (1997) Discrepancies between meta-analyses and subsequent large randomized controlled trials. New England Journal of Medicine, 337, 536542.
Lewis, G., Churchill, R. & Hotopf, M. (1997) Systematic reviews and meta-analysis. Psychological Medicine, 27, 37.
Maes, M., Vandoolaeghe, E. & Desnyder, R. (1996) Efficacy of treatment with trazodone in combination with pindolol or fluoxetine in major depression. Journal of Affective Disorders, 41, 201210.
Malison, R. T., Anand, A., Pelton, G. H., et al (1999) Limited efficacy of ketoconazole in treatment-refractory major depression. Journal of Clinical Psychopharmacology, 19, 466470.
Moher, D., Pham, B., Jones, A., et al (1998) Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet, 352, 609613.
Moreno, F. A., Gelenberg, A. J., Bachar, K., et al (1997) Pindolol augmentation of treatment-resistant depressed patients. Journal of Clinical Psychiatry, 58, 437439.
Nierenberg, A. A. & White, K. (1990) What next? A review of pharmacologic strategies for treatment resistant depression. Psychopharmacology Bulletin, 26, 429460.
Nolen, W. A., Haffmans, P. M., Bouvy, P. F., et al (1993) Monoamine oxidase inhibitors in resistant major depression. A double-blind comparison of brofaromine and tranylcypromine in patients resistant to tricyclic antidepressants. Journal of Affective Disorders, 28, 189197.
Perez, V., Soler, J., Puigdemont, D., et al (1999) A double-blind, randomized, placebo-controlled trial of pindolol augmentation in depressive patients resistant to serotonin reuptake inhibitors. Archives of General Psychiatry, 56, 375379.
Poirier, M. F. & Boyer, P. (1999) Venlafaxine and paroxetine in treatment-resistant depression. Doubleblind, randomised comparison. Psychiatry, 175, 1216.
Rybakowski, J. K., Suwalska, A. & Chlopocka-Wozniak, M., (1999) Potentiation of antidepressants with lithium or carbamazepine in treatment-resistant depression. Neuropsychobiology, 40, 134139.
Sackett, D. L. & Cook, R. J. (1995) The number needed to treat: a clinically useful measure of treatment effect. BMJ, 310, 452454.
Shelton, R. C., Tollefson, G. D., Tohen, M., et al (2001) A novel augmentation strategy for treating resistant major depression. American Journal of Psychiatry, 158, 131134.
Shergill, S. S. & Katona, C. L. E. (1996) Pharmacological choices after one antidepressant fails: a survey of UK psychiatrists. Journal of Affective Disorders, 43, 1925.
StataCorp (1999) Stata Statistical Software. College Station, Texas: Stata Corporation.
Stimpson, N., Lewis, G. & Agrawal, N. (2000) Pharmacological versus non-pharmacological interventions for refractory depression (Protocol for a Cochrane Review). Cochrane Library, issue 4. Oxford: Update Software.
Thase, M. E. & Rush, A. J. (1995) Treatment-resistant depression. In Psychopharmacology: The Fourth Generation of Progress (eds Bloom, F. E. & Kupfer, D.J.), pp. 10811097. New York: Raven Press.
Tyrer, P., Marsden, C. A., Casey, P., et al (1987) Clinical efficacy of paroxetine in resistant depression. Journal of Psychopharmacology, 1, 251257.
World Psychiatric Association (1974) Symposium on therapy resistant depression. Pharmacopsychiatry, 7, 69224.
Zohar, J., Shapira, B., Oppenheim, G., et al (1985) Addition of estrogen to imipramine in female resistant depressives. Psychopharmacology Bulletin, 21, 705706.
Zusky, P. M., Biederman, J., Rosenbaum, J. F., et al (1988) Adjunct low dose lithium carbonate in treatment-resistant depression: a placebo-controlled study. Journal of Clinical Psychopharmacology, 8, 120124.

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Randomised controlled trials investigating pharmacological and psychological interventions for treatment-refractory depression: Systematic review

  • Nicola Stimpson (a1), Niruj Agrawal (a2) and Glyn Lewis (a2)
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