E-Mail karger@karger.com Special Article Psychother Psychosom 2017;86:332–340 DOI: 10.1159/000480038 The Clinical Inadequacy of the Placebo Model and the Development of an Alternative Conceptual Framework Giovanni A. Fava   a, b Jenny Guidi   a Chiara Rafanelli   a Karl Rickels   c a  Department of Psychology, University of Bologna, Bologna, Italy; b  Department of Psychiatry, State University of New York at Buffalo, Buffalo, NY, and c  Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA lead to worsening of the condition. Maximizing patients’ ex- pectations does not necessarily result in sustained effects and, in due course, may actually lead to worsening of the condition (violation of expectations). In this paper, we out- line a multifactorial conceptual model that may have impli- cations for the design of clinical trials as well as for clinical practice, with special reference to psychopharmacology and psychotherapy. The effects of drug treatment may be potentiated by specific nonpharmacological treatment strategies, and this synergism may disclose significant dif- ferences against placebo. Medical outcomes may be unsat- isfactory not because technical interventions are missing, but because our conceptual models and thinking are inad- equate. © 2017 S. Karger AG, Basel Introduction The mechanisms of the placebo effect in medical and psychological therapies have been an endless source of debate. A recent comprehensive review of placebo re- sponses [1] suggested that they are mediated by expecta- tions, associative learning processes, and the quality of the patient-physician interaction. These components Keywords Placebo · Drug treatment · Psychotherapy · Illness behavior · Self-management · Treatment setting · Tolerance · Evidence-based medicine Abstract Placebo effects are often attributed to clinical interactions and contextual factors that affect expectations of the pa- tient about the treatment and result in symptom changes. The prevailing conceptualization consists of an undifferen- tiated placebo response that needs to be minimized in con- trolled investigations and maximized in clinical practice. However, treatment outcome is the cumulative result of the interaction of several classes of variables with a selected treatment: living conditions (housing, nutrition, work envi- ronment, social support), patient characteristics (age, sex, genetics, general health conditions, personality, well-be- ing), illness features and previous therapeutic experience, self-management, and treatment setting (physician’s atti- tude and attention, illness behavior). Such variables may be therapeutic or countertherapeutic, and are unlikely to be simply additive. In certain patients their interactive combi- nation may lead to clinical improvement, whereas in other cases it may produce no effect, and, in a third group, it may Received: May 20, 2017 Accepted after revision: August 7, 2017 Published online: November 3, 2017 Giovanni A. Fava, MD Department of Psychology, University of Bologna Viale Berti Pichat 5 IT–40127 Bologna (Italy) E-Mail giovanniandrea.fava  @  unibo.it © 2017 S. Karger AG, Basel www.karger.com/pps