Efficacité de la psychanalyse dans la dépression. Etude randomisée
Pragmatic randomized controlled trial of long-term psychoanalytic psychotherapy for treatment-resistant depression : the Tavistock Adult Depression Study (TADS).
Par : Fonagy P. (1,) Rost F. (2), Carlyle J.A. (2), McPherson S. (3), Thomas R. (2), Pasco Fearon R.M. (1), Goldberg D. (4), Taylor D. (2).
1 Research Department of Clinical, Educational and Health Psychology, University College London, London, UK
2 Adult Department, Tavistock & Portman NHS Foundation Trust, London, UK
3 School of Health and Human Sciences, University of Essex, Colchester, UK
4 Institute of Psychiatry, Psychology and Neuro science, King’s College London, London, UK
Pour citer cet article :
Fonagy P., Rost F., Carlyle J.A., McPherson S., Thomas R., Pasco Fearon R.M., Goldberg D., Taylor D. ( 2015). . Pragmatic randomized controlled trial of long-term psychoanalytic psychotherapy for treatment-resistant depression : the Tavistock Adult Depression Study (TADS). World Psychiatry. 14(3): 312–321. Published online 2015 Sep 25. doi: 10.1002/wps.20267
This pragmatic randomized controlled trial tested the effectiveness of long-term psychoanalytic psychotherapy (LTPP) as an adjunct to treatment-as-usual according to UK national guidelines (TAU), compared to TAU alone, in patients with long-standing major depression who had failed at least two different treatments and were considered to have treatment-resistant depression. Patients (N=129) were recruited from primary care and randomly allocated to the two treatment conditions. They were assessed at 6-monthly intervals during the 18 months of treatment and at 24, 30 and 42 months during follow-up. The primary outcome measure was the 17-item version of the Hamilton Depression Rating Scale (HDRS-17), with complete remission defined as a HDRS-17 score ≤8, and partial remission defined as a HDRS-17 score ≤12. Secondary outcome measures included self-reported depression as assessed by the Beck Depression Inventory – II, social functioning as evaluated by the Global Assessment of Functioning, subjective wellbeing as rated by the Clinical Outcomes in Routine Evaluation – Outcome Measure, and satisfaction with general activities as assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire. Complete remission was infrequent in both groups at the end of treatment (9.4% in the LTPP group vs. 6.5% in the control group) as well as at 42-month follow-up (14.9% vs. 4.4%). Partial remission was not significantly more likely in the LTPP than in the control group at the end of treatment (32.1% vs. 23.9%, p=0.37), but significant differences emerged during follow-up (24 months: 38.8% vs. 19.2%, p=0.03; 30 months: 34.7% vs. 12.2%, p=0.008; 42 months: 30.0% vs. 4.4%, p=0.001). Both observer-based and self-reported depression scores showed steeper declines in the LTPP group, alongside greater improvements on measures of social adjustment. These data suggest that LTPP can be useful in improving the long-term outcome of treatment-resistant depression. End-of-treatment evaluations or short follow-ups may miss the emergence of delayed therapeutic benefit.
Keywords : Treatment-resistant depression; delayed therapeutic effect; long-term treatment; psychoanalytic psychotherapy
This is the first fully randomized controlled trial of a manualized LTPP for treatment-resistant depression. Improvements in depression were modest but comparable between the LTPP and the control group until termination of treatment, while differences emerged from 24 months post-randomization, with the LTPP group mostly maintaining the gains achieved while the control group appeared to be at greater risk of relapse. At 2-year follow-up, almost one-third of the participants receiving LTPP were still in partial remission, compared with only 4% of those in the control group. At that time, 44% of the LTPP group no longer met diagnostic criteria for major depressive disorder, compared with 10% of those receiving TAU alone.
The effect sizes observed are in the medium range. The long-term outcomes of LTPP compare favorably with effect sizes reported in comprehensive reviews (3), including those used by the UK treatment recommendations (33). Studies that show stronger effects tend to observe patients in whom treatment resistance is less evident and lack information about long-term outcomes (43). Further comparisons, including longer manualized treatments based upon other (non-psychoanalytic) psychological therapy modalities such as CBT, are needed to establish the specificity of the therapeutic gain reported here.
As predicted, differences between the LTPP and the control group increased during follow-up on most measures. A Finnish longitudinal study of LTPP has reported a similar pattern with a less chronically depressed patient group (44), suggesting that LTPP may require some time post-treatment for its full effects to become evident (45). End-of-treatment evaluations or follow-ups that are too short may miss the emergence of this delayed therapeutic benefit.
While this study has ecological validity in that it employed a relatively unselected sample and incorporated a comparatively long follow-up, it has several limitations. First, the design of the study did not allow masking of patients to the treatment allocation, which may have generated an expectation bias. Second, although mixed-effects models are thought to be robust even to selective loss of data (46), we still failed to collect primary outcome data for over 25% of patients at 42 months, despite an unusually good level of retention for patients with depression of this severity. Third, the differences between the effects associated with the two treatments could have arisen as a result of the disparities between their respective numbers of contact hours, intensity, and quality of case management (47). Fourth, in spite of robust procedures, randomization yielded a difference between groups in education level, with associated asymmetries in employment and state benefits, which we were forced to adjust for statistically. Reanalysis in which the samples were balanced by selectively excluding patients did not alter the basic pattern of findings. Fifth, while we were concerned to measure outcome over an extended period, we omitted to include an interval depression measure such as the Longitudinal Interval Follow-up Evaluation (48). Sixth, since the study was planned and conducted by the developers of the intervention, there is a risk of allegiance bias (49). We tried to minimize this risk by having the primary outcome measure assessments made by interviewers who were blinded to the treatment condition. Seventh, these results were delivered by a single provider organization. This may limit generalizability. However, a multi-center German trial (the LAC Study) (50), testing LTPP using the same manual with a similar patient group, will shortly report.
In conclusion, while the benefit of both interventions for this severely affected group of patients with major depressive disorder was limited, a moderate difference emerged over long-term follow-up in favor of the LTPP condition. Further studies are needed to replicate this finding, ascertain its clinical utility, understand the mechanisms involved, and identify factors associated with response or non-response to treatment.
- Moussavi S, Chatterji S, Verdes E, et al. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet. 2007;370:851–8. [PubMed] [Google Scholar]
- Greden JF. The burden of disease for treatment-resistant depression. J Clin Psychiatry. 2001;62(Suppl. 16):26–31. [PubMed] [Google Scholar]
- Huhn M, Tardy M, Spineli LM, et al. Efficacy of pharmacotherapy and psychotherapy for adult psychiatric disorders: a systematic overview of meta-analyses. JAMA Psychiatry. 2014;71:706–15. [PubMed] [Google Scholar]
- Stimpson N, Agrawal N, Lewis G. Randomised controlled trials investigating pharmacological and psychological interventions for treatment-refractory depression. Systematic review. Br J Psychiatry. 2002;181:284–94. [PubMed] [Google Scholar]
- Thomas L, Kessler D, Campbell J, et al. Prevalence of treatment-resistant depression in primary care: cross-sectional data. Br J Gen Pract. 2013;63:e852–8. [PMC free article] [PubMed] [Google Scholar]
- Kubitz N, Mehra M, Potluri RC, et al. Characterization of treatment resistant depression episodes in a cohort of patients from a US commercial claims database. PLoS One. 2013;8:e76882. [PMC free article] [PubMed] [Google Scholar]
- McIntyre RS, Filteau MJ, Martin L, et al. Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord. 2014;156:1–7. [PubMed] [Google Scholar]
- Spijker J, van Straten A, Bockting CL, et al. Psychotherapy, antidepressants, and their combination for chronic major depressive disorder: a systematic review. Can J Psychiatry. 2013;58:386–92. [PubMed] [Google Scholar]
- Carvalho AF, Berk M, Hyphantis TN, et al. The integrative management of treatment-resistant depression: a comprehensive review and perspectives. Psychother Psychosom. 2014;83:70–88. [PubMed] [Google Scholar]
- Lam RW, Chan P, Wilkins-Ho M, et al. Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and metaanalysis. Can J Psychiatry. 2008;53:621–31. [PubMed] [Google Scholar]
- Daban C, Martinez-Aran A, Cruz N, et al. Safety and efficacy of Vagus Nerve Stimulation in treatment-resistant depression. A systematic review. J Affect Disord. 2008;110:1–15. [PubMed] [Google Scholar]
- Morishita T, Fayad SM, Higuchi MA, et al. Deep brain stimulation for treatment-resistant depression: systematic review of clinical outcomes. Neurotherapeutics. 2014;11:475–84. [PMC free article] [PubMed] [Google Scholar]
- Trivedi RB, Nieuwsma JA, Williams JW., Jr Examination of the utility of psychotherapy for patients with treatment resistant depression: a systematic review. J Gen Intern Med. 2011;26:643–50. [PMC free article] [PubMed] [Google Scholar]
- Hollon SD, DeRubeis RJ, Fawcett J, et al. Effect of cognitive therapy with antidepressant medications vs antidepressants alone on the rate of recovery in major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2014;71:1157–64. [PMC free article] [PubMed] [Google Scholar] Retracted
- Hollon SD, Ponniah K. A review of empirically supported psychological therapies for mood disorders in adults. Depress Anxiety. 2010;27:891–932. [PMC free article] [PubMed] [Google Scholar]
- Rawlins M. De Testimonio: on the evidence for decisions about the use of therapeutic interventions. Clin Med. 2008;8:579–88. [PMC free article] [PubMed] [Google Scholar]
- Driessen E, Van HL, Don FJ, et al. The efficacy of cognitive-behavioral therapy and psychodynamic therapy in the outpatient treatment of major depression: a randomized clinical trial. Am J Psychiatry. 2013;170:1041–50. [PubMed] [Google Scholar]
- Fonagy P. The effectiveness of psychodynamic psychotherapies: an update. World Psychiatry. 2015;14:137–50. [PMC free article] [PubMed] [Google Scholar]
- Leichsenring F, Klein S. Evidence for psychodynamic psychotherapy in specific mental disorders: a systematic review. Psychoanal Psychother. 2014;28:4–32. [Google Scholar]
- de Maat S, de Jonghe F, de Kraker R, et al. The current state of the empirical evidence for psychoanalysis: a meta-analytic approach. Harv Rev Psychiatry. 2013;21:107–37. [PubMed] [Google Scholar]
- Knekt P, Lindfors O, Laaksonen MA, et al. Quasi-experimental study on the effectiveness of psychoanalysis, long-term and short-term psychotherapy on psychiatric symptoms, work ability and functional capacity during a 5-year follow-up. Helsinki Psychotherapy Study Group. J Affect Disord. 2011;132:37–47. [PubMed] [Google Scholar]
- Leichsenring F, Rabung S. Long-term psychodynamic psychotherapy in complex mental disorders: update of a meta-analysis. Br J Psychiatry. 2011;199:15–22. [PubMed] [Google Scholar]
- Shedler J. The efficacy of psychodynamic psychotherapy. Am Psychol. 2010;65:98–109. [PubMed] [Google Scholar]
- Beck AT, Steer R, Brown G. Manual for Beck Depression Inventory – II (BDI-II) San Antonio: Psychological Corporation; 1996. [Google Scholar]
- Taylor D, Carlyle JA, McPherson S, et al. Tavistock Adult Depression Study (TADS): a randomised controlled trial of psychoanalytic psychotherapy for treatment-resistant/treatment-refractory forms of depression. BMC Psychiatry. 2012;12:60. [PMC free article] [PubMed] [Google Scholar]
- First MB, Spitzer RL, Gibbon M, et al. User’s Guide for the Structured Clinical Interview for DSM-IV Axis I Disorders – Research Version. New York: Biometrics Research, New York State Psychiatric Institute; 2001. [Google Scholar]
- Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62. [PMC free article] [PubMed] [Google Scholar]
- Taylor D. Treatment manuals and the advancement of psychoanalytic knowledge: the treatment manual of the Tavistock Adult Depression Study. Int J Psychoanalysis. 2015;96:845–75. [PubMed] [Google Scholar]
- McPherson S, Armstrong D. Negotiating ‘depression’ in primary care: a qualitative study. Soc Sci Med. 2009;69:1137–43. [PubMed] [Google Scholar]
- Andrews G. Reducing the burden of depression. Can J Psychiatry. 2008;53:420–7. [PubMed] [Google Scholar]
- Milton J. Psychoanalysis and cognitive behaviour therapy – rival paradigms or common ground? Int J Psychoanal. 2001;82:431–47. [PubMed] [Google Scholar]
- Jones EE. Therapeutic action: a guide to psychoanalytic therapy. Northvale: Jason Aronson; 2000. [Google Scholar]
- National Institute for Health and Clinical Excellence. Depression in adults: the treatment and management of depression in adults. Clinical Guideline 90. London: National Institute for Health and Clinical Excellence; 2009. [Google Scholar]
- Beecham JK, Knapp MRJ. Costing psychiatric interventions. In: Thornicroft G, Brewin C, Wing JK, editors. Measuring mental health needs. London: Gaskell/Royal College of Psychiatrists; 1992. pp. 163–83. [Google Scholar]
- Reimherr FW, Amsterdam JD, Quitkin FM, et al. Optimal length of continuation therapy in depression: a prospective assessment during long-term fluoxetine treatment. Am J Psychiatry. 1998;155:1247–53. [PubMed] [Google Scholar]
- Frank E, Prien RF, Jarrett RB, et al. Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Arch Gen Psychiatry. 1991;48:851-5. [PubMed] [Google Scholar]
- Hilsenroth MJ, Ackerman SJ, Blagys MD, et al. Reliability and validity of DSM-IV axis V. Am J Psychiatry. 2000;157:1858–63. [PubMed] [Google Scholar]
- Evans C, Mellor-Clark J, Margison F, et al. CORE: Clinical Outcomes in Routine Evaluation. J Ment Health. 2000;9:247–55. [Google Scholar]
- Endicott J, Nee J, Harrison W, et al. Quality of Life Enjoyment and Satisfaction Questionnaire: a new measure. Psychopharmacol Bull. 1993;29:321–6. [PubMed] [Google Scholar]
- Statacorp. Stata statistical software: Release 14. College Station: StataCorp LP; 2015. [Google Scholar]
- Bateman A, Fonagy P. Randomized controlled trial of outpatient mentalization-based treatment versus structured clinical management for borderline personality disorder. Am J Psychiatry. 2009;166:1355–64. [PubMed] [Google Scholar]
- Rabe-Hesketh S, Skrondal A. Multilevel and longitudinal modeling using STATA. 3rd ed. College Station: Stata Press; 2012. [Google Scholar]
- Keller MB, McCullough JP, Klein DN, et al. A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med. 2000;342:1462–70. [PubMed] [Google Scholar]
- Knekt P, Lindfors O, Harkanen T, et al. Randomized trial on the effectiveness of long-and short-term psychodynamic psychotherapy and solution-focused therapy on psychiatric symptoms during a 3-year follow-up. Helsinki Psychotherapy Study Group. Psychol Med. 2008;38:689–703. [PubMed] [Google Scholar]
- Muratori F, Picchi L, Bruni G, et al. A two-year follow-up of psychodynamic psychotherapy for internalizing disorders in children. J Am Acad Child Adolesc Psychiatry. 2003;42:331–9. [PubMed] [Google Scholar]
- Verbeke G, Molenberghs G. Linear mixed models for longitudinal data. New York: Springer; 2000. [Google Scholar]
- Rossouw TI, Fonagy P. Mentalization-based treatment for self-harm in adolescents: a randomized controlled trial. J Am Acad Child Adolesc Psychiatry. 2012;51:1304–13. [PubMed] [Google Scholar]
- Keller MB, Lavori PW, Friedman B, et al. The Longitudinal Interval Follow-up Evaluation. A comprehensive method for assessing outcome in prospective longitudinal studies. Arch Gen Psychiatry. 1987;44:540–8. [PubMed] [Google Scholar]
- Luborsky L, Diguer L, Seligman DA, et al. The researcher’s own therapy allegiances: a “wild card” in comparisons of treatment efficacy. Clin Psychol Sci Pract. 1999;6:95–106. [Google Scholar]
- Beutel ME, Leuzinger-Bohleber M, Ruger B, et al. Psychoanalytic and cognitive-behavior therapy of chronic depression: study protocol for a randomized controlled trial. Trials. 2012;13:117. [PMC free article] [PubMed] [Google Scholar]