“A good doctor treats the disease. A great doctor treats the person who has the disease.”
In medicine today, technological healing has eclipsed interpersonal aspect of healing. Today’s doctors have less time taking care of illness and alleviating suffering than treating diseases. We psychiatrists seem to be the last bastion practicing the healing art of medicine, which emphasizes positive therapeutic relationship, good communication skills, and relief of pain and suffering. Conceivably, placebo effect bridges the mind-body gap and encapsulates the art of caring in clinical practice.
Psychiatrists use the healing power of words and drugs in clinical practice. About 50 years ago, when a major shift of focus from psychodynamic to biological orientation took place in the field, hopes were running high about pharmacological cure of mental illnesses. Unrealistic expectations created by the biomedical model appear to be on shaky (unscientific) grounds. Multicenter, real-world trials of psychotropic drugs have failed to show a robust effectiveness in clinical practice, and only a marginal intra-class difference between drugs.1–3 The psychotherapy research literature reveals the equivalence paradox (ie, all the bona fide psychotherapies regardless of their specific treatment techniques have equally efficacious global outcomes), and that effective therapists behave similarly in conducting therapy irrespective of their theoretical orientation.4 It is difficult to devise double-blind studies of psychotherapies because the therapist knows what treatment is being given and the dynamic ingredients of psychotherapy and placebo effects are virtually inseparable. In their groundbreaking work, Frank and Frank5 argued that there are “curative” features shared by all psychotherapies; these are:
A person in distress.
Emotionally charged interaction with an expert.
A healing setting conducive to a safe, soothing environment that strengthens expectation of help.
Both the healer and a person are vested in the explanation for the condition, which insures hope.
A healing ritual that allows the healer to show his mastery of the technique, win over the confidence, further cement the alliance, and enhance expectations of a positive outcome.5
Moerman6 argued that psychotherapy “is nothing but a good human interaction” that activates expectancy and hope for a successful outcome. Kradin7 suggested that psychotherapy reawakens a dormant soothing pattern of interaction with an early caregiver wherein the therapeutic relationship results in positive outcome more than any specific techniques.
A meta-analysis of placebo-controlled antidepressant studies showed only about a 25% drug benefit and a 50% benefit from the placebo component of treatment.8 Hegerl and Mergl,9 based on their mathematical model assumptions, have argued that in standard clinical practice, a drug’s efficacy might be substantially higher than in controlled trials due to a significantly higher nonspecific treatment effect (ie, placebo response). Thus, a large part of the observed efficacy of many drug treatments may derive from non-pharmacodynamic factors, and every medical treatment may contain embedded placebo effects unbeknownst to either the physician or the patient.
It remains enigmatic why placebo effects are sometimes larger than the effects of properly evaluated evidence-based treatments, the so-called “efficacy paradox.”10
Placebo effects are well-nigh impossible to speculate in clinical practice. They may range from 0% to 100%. Furthermore, placebo responders are difficult to characterize. It is possible to create treatment conditions that will set the stage to promote placebo responses. In 2002, a National Institutes of Health placebo conference emphasized the importance of identifying the qualities of placebo enhancing practitioners.11 Practicing clinicians ought to strive to maximize placebo effects to improve treatment outcomes. Another placebo conference held in 2012 explored ways to ethically promote placebo responses in clinical practice.12
Placebo effects have been described variously as psychosocial effects,13 context effects,14 meaning responses,15 and positive-care effects.16 They generally include the doctor-patient relationship (which accounts for a significant portion of the variance in outcomes), therapeutic focus (having a purposeful focus leads to superior outcomes), patient attributes (eg, commitment, engagement), self-fulfilling prophecy of a good outcome (expectation of success by clinicians and patients tends to produce success), and patient and therapist characteristics.17 The doctor-patient interaction sets in motion a form of interpersonal healing that maximizes the placebo response, starting with the anticipation of recovery or relief from distress when the initial appointment is made. Even though psychiatrists no longer carry stethoscopes or wear white coats, we still display the symbols of our prestige or professional success by hanging diplomas, certificates, awards and honors, creating a soothing décor, and being professional in dress and manner to create a healing setting. The first clinical encounter is often vested with magical qualities, and a good therapist intuitively knows how to prime the pump for better therapeutic outcomes. This helps to create a positive holding environment, à la Winnicot.18
Human Factors Matter
In an oft-cited study, Strupp and Hadley19 showed that university professors with renowned reputations for warmth and trustworthiness but no previous therapy experience as therapists could produce good outcomes comparable to those of therapists with more than 20 years’ experience. They described this as the “healing effects of a benign human relationship.” Krupnick et al.20 showed a robust association between therapeutic alliance and improvement in both drug and placebo conditions in a National Institute of Mental Health (NIMH) study that provided empirical support to the notion that being an effective psychopharmacologist goes beyond merely handing out prescriptions. However, Strunk et al.21 and Quitkin22 reported that higher levels of therapeutic support did not deter later relapses in patients receiving placebo pills.
McKay et al.23 reanalyzed data from 112 patients treated by 18 psychiatrists (50% in a drug arm, 50% in a placebo arm) from the NIMH depression collaborative research program to show that therapeutic alliance was the largest contributor to improvement in depression compared to any other modality of treatment. The placebo-enhancing psychiatrists had better outcomes with inert pills than other psychiatrists had with drugs; however, the characteristics of effective psychiatrists were not described.
Placebo-enhancing practitioners strive to develop a “sustained partnership” with patients using some or all of the following qualities, as summarized by Brody.24
- Caring, empathy, and sensitivity.
- Ability to adapt medical care goals to the patient’s needs and values.
- Encouragement of the patient to participate fully in decision-making.
- Confidence, enthusiasm, affability, willingness to be reassuring.
- Perception as warm and friendly, trustworthy, and reliable by patients.
Interpersonal Skills and Communication Styles
There is a long-heralded and deep connection between healing and human relationships. Healing rituals have been known to occur in all human societies since antiquity. The efficacy of self-healing is learned by the human infant through a nurturing mother, and that healing power is later transferred to physicians who take care of the sick as “culturally sanctioned parental figures.”25 Kradin7 made the argument that people with secure attachment styles are more capable of activating their inner health-restoring mechanism to get greater benefit from drugs and/or psychotherapy. On the other hand, patients lacking early-life positive caring experiences are more likely to develop side effects from medications (ie, “nocebo response”).7 The help-seeking behavior itself is a strong factor in evoking placebo effects by offering an opportunity to experience an implicitly remembered interaction with a soothing early caregiver. Alternately, it can also be a reenactment of remembrance of past wellness.26
Nowadays, good communication and interpersonal skills are probably more emphasized in major consumer-service industries than in clinical medicine. Yet, it remains the bedrock upon which the art of medicine and the doctor-patient relationship are based. It includes both verbal and nonverbal communications and encompasses empathy; ability to listen without interruption; tone and rhythm of voice (prosody); and ability to project a warm, reassuring, and hopeful persona. Nonverbal communication includes eye contact, posture, facial expression, touch, dress, and professional manner and speaks silently to the patient’s right brain and limbic system, communicating our inner feelings, attitudes, and values much in the same manner as a patient’s early caregivers communicated with him or her before the development of verbal communication in the first 3 years of life.7 For obvious reasons, psychiatrists do not conduct physical examinations, and the specter of therapeutic boundary crossing argues against touching a patient under most circumstances; however, laying of hands has been an important part of healing ritual that has mostly been appropriated by complementary and alternative medicine therapists successfully. It has been an essential channel of communication for children’s caregivers. Touch can communicate multiple positive emotions: joy, love, gratitude, and sympathy. Warm touch stimulates release of oxytocin, which enhances a sense of trust and attachment. Touch is the best way to comfort the patient.27 Modern psychiatry is “low-tech” but ought to be “high-touch.”
Verbal communication targets the left brain cortical centers and gives meaning and other symbolic functions to patient narrative. As stated by Brody, “most people attach meaning to important events in their lives by implicitly or explicitly constructing narratives about the events.” Brody28 posited that such narratives or “story work” allow the physician and the patient with chronic complex problems to work with the issue of the meaning of illness. Learning to mine a patient’s narrative can help the physician develop the courage to bear witness to life’s unfair losses and random tragedies, which helps healing.29 Equally important is prosody of speech — how something is said is said is as important as what is said. Prosody appeals to the right brain, strongly influences the autonomic nervous system and hypothalamic pituitary-adrenal system through the limbic pathways, and can regulate non-verbal healing responses.30 Many patients come to psychiatrist with a fervent desire to be listened to and understood. Active listening, in conjunction with inaction, contributes to structuring the patients’ mind-body states and promotes placebo response. Not listening appropriately may be sensed as a rejection and can elicit a nocebo response.7
Through empathic listening, patients perceive their doctor’s consistent, professional concern for their feelings. In one study, doctors’ functional MRI scans showed that both effective treatments and placebo therapy activate the same brain regions, and that physicians’ empathy influenced positive outcomes in pain treatments.31 More than 50% of chronically ill psychiatric patients do not adhere to their medications as prescribed causing relapses, repeated admissions, and a great financial burden on health care. A meta-analysis in cancer patients found that the cornerstone of patient compliance with medication is professional empathy.32 Furthermore, doctors’ communication styles also promote a sense of empowerment and mastery in patients as it helps them believe their situation is hopeful and their actions will promote recovery. Studies have indicated that a sense of control over a situation, even if the individual actually has no control, has a positive effect on health.32 This decreases demoralization and increases patients’ self-efficacy to work toward a desired outcome, which brings us to Frank’s concept of demoralization. A person coming to see a psychiatrist often has significant distress, dysphoria and a loss of meaning, a sense of failure, and feeling of incompetency in solving his or her own problems. The patient’s coping mechanisms are depleted; he or she is merely trying to get by, but also existing in a state of heightened suggestivity. The patient expects relief from suffering by whatever means — medication or talk therapy. When the doctor holds out hope for help, it can impact the machinery of perception, rekindling the sense of control and being able to achieve an outcome. It can revive the realistic plans of making genuine choices.33
Daniel Moerman, who was eager to replace the term “placebo effect” with the alternative term “meaning response,” claimed that psychotherapy is all about what it means to the patient.15 Even in biomedical healing, when the patient receives meaningful communication along with an inert tablet or injection, positive changes can happen, and the clinician does not even need to deceive. By honestly informing the patient of a pending, effective treatment, placebo effect regularly occurs in medical settings in which there are no placebos in play. Many studies show that a physician’s enthusiasm for treatment is quite effective on a patient’s response.
The Patient’s Perspective
Most patients struggling with serious mental illnesses often feel burdened with functional disabilities and repeated relapses and often have to deal with byzantine bureaucracy, which robs them of their dignity, self-efficacy, control, and independence. Against this background, our patients value friendliness, warmth, and acceptance by a clinician who can validate their suffering, who creates hope, and empowers them to succeed. Seeking feedback, either written or verbal, will go a long way to satisfy the patient and will increase the benefits from therapy or medication.34 Psychiatrists should also take placebo response history with every patient, which includes past treatment history, occurrence of side effects, and their experiences with previous doctors.
Eisenberg35 put it succinctly: “In the past, we practiced ‘brainless’ psychiatry. Now we are practicing ‘mindless’ psychiatry.” In this era of biological reductionism and the delusions of precision of our drugs,36 some of our most potent tools are wasted (ie, therapeutic alliances, generating hope and expectancy, meaning effects; reversing demoralization, etc.) Giving patients the best effective treatment along with positive expectations, realistic optimism, and hope strengthens the healing relationship, maximizes the placebo effect, and increases their confidence in the health care system.37
Since social, psychological, and biological processes accompany every biomedical intervention, understanding the placebo effects bridges the gap between the brain and the mind. It is scientific revalidation of what we have known all along: that the therapeutic relationship is an important part of the healing process. It also shows that health is not just an individual achievement, but rather from birth and through moments of illness, it is potentiated from the help of another individual.
- Lieberman JA. Comparative effectiveness of antipsychotic drugs. A commentary on: Cost Utility Of The Latest Antipsychotic Drugs In Schizophrenia Study (CUtLASS 1) and Clinical Antipsychotic Trials Of Intervention Effectiveness (CATIE). Arch Gen Psychiatry. 2006;63(10):1069–1072. doi:10.1001/archpsyc.63.10.1069 [CrossRef]
- Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163(1):28–40. doi:10.1176/appi.ajp.163.1.28 [CrossRef]
- Bowden CL, Perlis RH, Thase ME, et al. Aims and results of the NIMH systematic treatment enhancement program for bipolar disorder (STEP-BD). CNS Neurosci Ther. 2012;18(3):243–249. doi:10.1111/j.1755-5949.2011.00257.x [CrossRef]
- Wampold BE, Mondin GW, Moody M, et al. A meta-analysis of outcome studies comparing bona fide psychotherapies. Psychological Bulletin. 1997;122(3):203–215. doi:10.1037/0033-2909.122.3.203 [CrossRef]
- Frank JD, Frank JB. Persuasion and Healing: A Comparative Study of Psychotherapy. Baltimore, MD: Johns Hopkins University Press; 1991.
- Moerman DE. Meaning, Medicine, and the Placebo Effect. England: Cambridge University Press; 2002. doi:10.1017/CBO9780511810855 [CrossRef]
- Kradin RA. The Placebo Response and the Power of Unconscious Healing. New York, NY: Routledge; 2008.
- Kirsch IS, Sapirstein G. Listening to Prozac but hearing placebo: a meta-analysis of antideprssant medication. Prevention & Treatment. 1998;1(2):No pagination specified; article 2a. doi:10.1037/1522-37126.96.36.199a [CrossRef]
- Hegerl U, Mergl R. The clinical significance of antidepressant treatment effects cannot be derived from placebo-verum response differences. J Psychopharmacol. 2010;24(4):445–448. doi:10.1177/0269881109106930 [CrossRef]
- Kaptchuk TJ, Kelley JM, Conboy LA, et al. Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome. BMJ. 2008;336(7651):999–1003. doi:10.1136/bmj.39524.439618.25 [CrossRef]
- Guess HA, Kleinmann A, Kusek JW, Engel LW. The Science of Placebo: Toward an Interdisciplinary Research Agenda. London: BMJ Books; 2002.
- Samueli Institute, Theophrastus-Stiftung, National Center for Complementary and Alternative Medicine, National Institute on Drug Abuse of the National Institutes of Health, Agency for Healthcare Research and Quality. Using Placebo Responses in Clinical Practice; January19–20, 2012; Bethesda, MD.
- Finniss DG, Kaptchuk TJ, Miller F, Benedetti F. Biological, clinical, and ethical advances of placebo effects. Lancet. 375(9715):686–695.
- Miller FG, Kaptchuk TJ. The power of context: reconceptualizing the placebo effect. J R Soc Med. 2008;101(5):222–225. doi:10.1258/jrsm.2008.070466 [CrossRef]
- Moerman DE, Jonas WB. Deconstructing the placebo effect and finding the meaning response. Ann Intern Med. 2002;136(6):471–476. doi:10.7326/0003-4819-136-6-200203190-00011 [CrossRef]
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- Strupp HH, Hadley SW. Specific vs. nonspecific factors in psychotherapy. A controlled study of outcome. Arch Gen Psychiatry. 1979;36(10):1125–1136. doi:10.1001/archpsyc.1979.01780100095009 [CrossRef]
- Krupnick JL, Sotsky SM, Simmens S, et al. 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(3):532–539. doi:10.1037/0022-006X.64.3.532 [CrossRef]
- Strunk DR, Stewart MO, Hollon SD, et al. Can pharmacotherapists be too supportive? A process study of active medication and placebo in the treatment of depression. Psychol Med. 2010;40(8):1379–1387. doi:10.1017/S0033291709991553 [CrossRef]
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- McKay KM, Imel ZE, Wampold BE. Psychiatrist effects in the psychopharmacological treatment of depression. J Affect Disord. 2006;92(2–3):287–290. doi:10.1016/j.jad.2006.01.020 [CrossRef]
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