Background: Previous studies have shown that in psychotherapy alliance is a predictor of symptomatic change, even while accounting for the temporal precedence between alliance and symptoms. However, the extent to which alliance predicts outcomes in psychopharmacology is yet to be fully investigated considering the fact that alliance can be the result, rather than the cause, of symptomatic change. The current prospective study examined whether the alliance predicts outcomes in psychopharmacology, while controlling for previous symptomatic change throughout the course of treatment. Methods: Data from a psychopharmacological randomized controlled trial for the treatment of adult major depression (n = 42), including the patients' rating of the alliance with the physicians, were analyzed. Multilevel models controlling for autoregressive lag of the dependent variable were used in all analyses to examine the effect of alliance on outcome. Results: The effect of alliance on outcome, while controlling for prior symptomatic levels, was significant and restricted to the middle phase of treatment (week 4, p = 0.005), when most of the reductions in symptoms were observed. Exploratory analyses of the differences between placebo and medication conditions suggest that the differences between the patients in their average alliance levels predicted a greater reduction in symptoms in the placebo compared to the medication conditions (p = 0.008). The main limitation is the small cohort size. Conclusions: The findings suggest an effect of alliance on outcome in psychopharmacology, which is not merely the result of previous symptomatic levels. This effect may be more robust in conditions that do not include active treatment (placebo), possibly serving as a compensatory effect.

Keywords:
Depression, Alliance, Antidepressant treatment, Psychopharmacology, Placebo effect, Therapy process
1.
Hatcher RL, Barends AW: How a return to theory could help alliance research. Psychotherapy 2006;43:292-299.
2.
Bordin E: The generalizability of the psychoanalytic concept of the working alliance. Psychotherapy 1979;16:252-260.
3.
Horvath AO, Del Re AC, Fluckiger C, Symonds D: Alliance in individual psychotherapy. Psychotherapy 2011;48:9-16.
4.
DeRubeis RJ, Feeley M: Determinants of change in cognitive therapy for depression. Cognit Ther Res 1990;14:469-482.
5.
Barber JP: Toward a working through of some core conflicts in psychotherapy research. Psychother Res 2009;19:1-12.
6.
DeRubeis RJ, Brotman MA, Gibbons CJ: A conceptual and methodological analysis of the nonspecifics argument. J Clin Psychol 2005;12:174-183.
7.
Barber JP, Luborsky L, Crits-Christoph P, Thase ME, Weiss R, Frank A, Onken LS, Gallop R: Therapeutic alliance as a predictor of outcome in treatment of cocaine dependence. Psychother Res 1999;9:54-73.
8.
Barber JP, Connolly MB, Crits-Christoph P, Gladis L, Siqueland L: Alliance predicts patients' outcome beyond in-treatment change in symptoms. J Consult Clin Psychol 2000;68:1027-1032.
9.
Zilcha-Mano S, Dinger U, McCarthy K, Barber J: Does alliance predict symptomatic change, or is it the other way around? J Consult Clin Psychol 2014;82:931-935.
10.
Crits-Christoph P, Gibbons MBC, Mukherjee D: Psychotherapy process-outcome research; in Lambert MJ (ed.): Bergin and Garfield's Handbook of Psychotherapy and Behavior Vhange, ed 6. Hoboken, Wiley, 2013, pp 298-340.
11.
Uhlenhuth EH, Rickels K, Fisher S, Park LC, Lipman RS, Mock J: Drug, doctor's verbal attitude and clinic setting in the symptomatic response to pharmacotherapy. Psychopharmacologia 1966;9:392-418.
12.
Bech P: Karl Rickels: a tribute on his 90th birthday. Psychother Psychosom 2014;83:131-135.
13.
Krupnick JL, Sotsky SM, Simmens S, Moyer J, Elkin I, Watkins J, Pilkonis PA: The role of the therapeutic alliance in psychotherapy and pharmacotherapy outcome: findings in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. J Consult Clin Psychol 1996;64:532-539.
14.
Wolfaardt UB, Reddon JR, Joyce AS: Assessing the efficacy of antidepressants: the transactional paradigm. Med. Hypotheses 2005;64:1229-1236.
15.
Ekeland T: The healing context and efficacy in psychotherapy: psychotherapy and placebo phenomenon. Int J Psychother 1997;2:77-87.
16.
Marshall M, Gray A, Lockwood A, Green R: Case management for people with severe mental disorders. Cochrane Database Syst Rev 2000;2:CD0000050.
17.
Dilallo JJ, Weiss G: Motivational interviewing and adolescent psychopharmacology. J Am Acad Child Adolesc Psychiatry 2009;48:108-113.
18.
Strunk DR, Stewart MO, Hollon SD, DeRubeis RJ, Fawcett J, Amsterdam JD, Shelton RC: Can pharmacotherapists be too supportive? A process study of active medication and placebo in the treatment of depression. Psychol Med 2010;40:1379-1387.
19.
Posternak MA, Zimmerman M: Therapeutic effect of follow-up assessments on antidepressant and placebo response rates in antidepressant efficacy trials: meta-analysis. J Ment Sci 2007;190:287-292.
20.
Rutherford B, Sneed J, Devanand D, Eisenstadt R, Roose S: Antidepressant study design affects patient expectancy: a pilot study. Psychol Med 2010;40:781-788.
21.
Rutherford BR, Marcus SM, Wang P, Sneed JR, Pelton G, Devanand D, Duan N, Roose SP: A randomized, prospective pilot study of patient expectancy and antidepressant outcome. Psychol Med 2013;43:975-982.
22.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders: DSM-IV_TR, ed 4. Washington, American Psychiatric Association, 2000.
23.
Hamilton M: A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.
24.
Guy W: Clinical Global Impressions. New Clinical Drug Evaluation Unit (ECDEU) Assessment Manual for Psychopharmacology. Rockville, National Institute of Mental Health, 1976, pp 218-222.
25.
Gaston L, Marmar CR: The California Psychotherapy Alliance Scales; in Horvath AO, Greenberg LS (ed): The Working Alliance: Theory, Research, and Practice. Oxford, Wiley, 1994, pp 85-108.
26.
First MB, Spitzer RL, Gibbon M, Williams JBW: Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV). Washington, American Psychiatric Press, 1996.
27.
Fawcett J, Epstein P, Fiester SJ, Elkin I, Autry JH: Clinical management - imipramine/placebo administration manual: NIMH Treatment of Depression Collaborative Research Program. Psychopharmacol Bull 1987;23:309-324.
28.
Littell RC, Milliken GA, Stroup WW, Wolfinger RD, Schabenberger O: SAS for Mixed Models, ed 2. Cary, SAS Institute, 2006.
29.
Collins LM, Sayer AG: New Methods for the Analysis of Change. Washington, American Psychological Association, 2001.
30.
Zilcha-Mano S, Dinger U, McCarthy KS, Barrett MS, Barber JP: Changes in well-being and quality of life in a randomized trial comparing dynamic psychotherapy and pharmacotherapy for major depressive disorder. J Affect Disord 2014;152:538-542.
31.
Curran PJ, Bauer DJ: The disaggregation of within-person and between-person effects in longitudinal models of change. Annu Rev Psychol 2011;62:583-619.
32.
Raudenbush SW, Bryk AS: Hierarchical Linear Models, ed 2. Thousand Oaks, Sage, 2002.
33.
Harrington A: The Placebo Effect. Cambridge, Harvard University Press, 1999.
34.
Frank JD: Persuasion and Healing. Baltimore, Johns Hopkins University Press, 1961.
35.
Rutherford BR, Roose SP: A model of placebo response in antidepressant clinical trials. Am J Psychiatry 2013;170:723-733.
36.
Zilcha-Mano S, Barber J: Instability of depression severity at intake as a moderator of outcome in treatment for major depressive disorder. Psychother Psychosom 2014;83:382-383.
37.
Papakostas GI, Fava M: Does the probability of receiving placebo influence clinical trial outcome? A meta-regression of double-blind, randomized clinical trials in MDD. Eur Neuropsychopharmacol 2009;19:34-40.
38.
Fava GA, Guidi J, Rafanelli C, Sonino N: The clinical inadequacy of evidence-based medicine and the need for a conceptual framework based on clinical judgment. Psychother Psychosom 2015;84:1-3.
39.
Kenny D, Harackiewicz J: Cross-lagged panel correlation: practice and promise. J Appl Psychol 1979;64:372-379.
40.
Di Blasi Z, Kleijnen J: Context effects: powerful therapies or methodological bias? Eval Health Prof 2003;26:166-179.
© 2015 S. Karger AG, Basel
2015
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.