During the past 2 decades, psychiatry has benefited from an increasingly evidence-based perspective and a proliferation of safer, more tolerable, and perhaps more effective treatments. Despite these advances, however, treatment outcomes are not substantially better than they were a quarter of a century ago.1 Treatment resistance remains a serious problem across psychiatric diagnoses.2 One likely reason that outcomes have not improved substantially is that as the pendulum has swung from a psychodynamic framework to a biological one, the impact of meaning (ie, the role of psychosocial factors in treatment-refractory illness) has been relatively neglected, and psychiatrists have lost some potent tools for working with the most troubled patients.
Psychodynamic psychopharmacology explicitly acknowledges and addresses the central role of meaning and interpersonal factors in pharmacological treatment.3 This approach recognizes that many of the core discoveries of psychoanalysis (the unconscious, conflict, resistance, transference, defense) are powerful factors in the complex relationships between the patient, the illness, the doctor, and the medications. In many cases, these factors are largely concordant with treatment and do not need to be addressed in order for treatment to be effective. However, in patients who are treatment-resistant, it is likely that psychodynamic factors (that may well be unconscious) are deeply at odds with therapeutic goals.
Dynamic factors in psychopharmacology
There is currently a small but impressive evidence base that shows that psychological and interpersonal factors play a pivotal role in pharmacological treatment responsiveness.
An analysis of the data from a large, NIMH-funded, multicenter, placebo-controlled trial of the treatment of depression found a provocative treater x medication effect.4 While the most effective prescribers who provided active drug (antidepressant) had the best results, it was also true that the most effective one-third of prescribers had better outcomes with placebos than the least effective one-third of prescribers had with active drug. This suggests that how the doctor prescribes is actually more important than what the doctor prescribes!
A series of meta-analyses of FDA databases (examining an unbiased sample, including negative, unpublished studies) shows that although antidepressant medications are effective, the placebo effect accounts for between 76% and 81% of treatment effectiveness.5-7 Placebo does not mean imaginary or untrue. Placebos produce real, clinically significant, and objectively measurable improvements in a wide range of conditions, including psychiatric disorders.8,9 And, placebo responses produce measurable changes in brain activity that largely overlap medication-induced improvements.10 The patient’s desire to change and a positive transference to the doctor and his or her medications can mobilize profound self-healing capacities—capacities that appear to be even more potent than the medication’s active ingredient.
Although most of our patients ask us for help, many are conflicted about getting well if their illness has created some conscious or unconscious benefit. If a patient is not “ready to change,” it is unlikely that a medication, however potent, will produce a therapeutic effect. Beitman and colleagues11 found, in a placebo-controlled trial, that patients who received a benzodiazepine for anxiety and who were highly motivated to change had the most robust response. However, placebo recipients who were highly motivated to change had a greater reduction in anxiety than patients who took the active drug but were less ready to change. Readiness to change was found to be the single most powerful determinant of treatment effectiveness—even more potent than type of therapy (ie, active vs placebo).
In 1912, Freud12 noted that the unobjectionable positive transference (consisting of such things as the patient’s belief in the doctor’s salutary intentions, the wish to use the doctor to get better, and the desire to win the doctor’s love or esteem by genuinely trying to get better) was a key factor in the patient’s ability to overcome symptoms. This unobjectionable positive transference, ie, the therapeutic alliance, is one of the most potent ingredients of treatment.12,13 In a large, placebo-controlled, multicenter trial of treatments of depression, Krupnick and colleagues14 showed that patients were most likely to respond when they received the active drug and had a strong therapeutic alliance. Those least likely to respond when given placebo had a poor therapeutic alliance. Patients who received placebo and who had a strong treatment alliance had a significantly more robust therapeutic response than patients who received an antidepressant but had a poor therapeutic alliance. Taken together, these studies examining the relative effectiveness of biologically and symbolically active aspects of the medication suggest that meaning effects in psychopharmacology are more potent than biological effects.4-7,11,13,14
Just as positive transferences to the doctor or drug lead to positive responses, negative transferences are likely to lead to negative responses. Patients who have been abused or neglected by caregivers in the past or those who otherwise feel vulnerable to authority figures (either because of social disadvantage or a propensity to acquiesce) are prone to nocebo responses.15,16 The obverse of the placebo response, nocebo responses occur when patients expect (either consciously or unconsciously) to be harmed. Many patients who experience intolerable adverse effects to medications are nocebo responders. It comes as no surprise that these patients are likely to become treatment-resistant.
1. Kessler RC, Berglund P, Demler O, et al; National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003;289:3095-3105.
2. Plakun EM. A view from Riggs—treatment resistance and patient authority: I. A psychodynamic perspective. J Am Acad Psychoanal Dyn Psychiatry. 2006;34:349-366.
3. Mintz D, Belnap B. A view from Riggs: treatment resistance and patient authority—III. What is psychodynamic psychopharmacology? An approach to pharmacologic treatment resistance. J Am Acad Psychoanal Dyn Psychiatry. 2006;34:581-601.
4. McKay KM, Imel ZE, Wampold BE. Psychiatrist effects in the psychopharmacological treatment of depression. J Affect Disord. 2006;92:287-290.
5. Kirsch I, Sapirstein G. Listening to Prozac but hearing placebo: a meta-analysis of antidepressant medication. June 26, 1998. http://psycnet.apa.org/?fa=main.doiLanding&doi=10.1037/1522-37188.8.131.52a. Accessed June 24, 2009.
6. Khan A, Warner HA, Brown WA. Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials: an analysis of the Food and Drug Administration database. Arch Gen Psychiatry. 2000;57:311-317.
7. Kirsch I, Moore TJ, Scoboria A, Nicholls SS. The emperor’s new drugs: an analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration. Prevention & Treatment 5, Article 23. 2002. http://www.journals.apa.org/prevention/volume5/pre0050023a.html.
8. Brody H. Placebos and the Philosophy of Medicine. Chicago: University of Chicago Press; 1977.
9. Moerman DE, Jonas WB. Deconstructing the placebo effect and finding the meaning response. Ann Intern Med. 2002;136:471-476.
10. Mayberg HS, Silva JA, Brannan SK, et al. The functional neuroanatomy of the placebo effect. Am J Psychiatry. 2002;159:728-737.
11. Beitman BD, Beck NC, Deuser WE, et al. Patient Stage of Change predicts outcome in a panic disorder medication trial. Anxiety. 1994;1:64-69.
12. Freud S. The dynamics of transference. The Standard Edition of the Complete Psychological Works of Sigmund Freud. Vol 12. London: Hogarth Press; 1912/1958.
13. Blatt SJ, Zuroff DC. Empirical evaluation of the assumptions in identifying evidence-based treatments in mental health. Clin Psychol Rev. 2005;25:459-486.
14. Krupnick JL, Sotsky SM, Simmens S, et al. The role of 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.
15. Hahn RA. The nocebo phenomenon: scope and foundations. In: Harrington A, ed. The Placebo Effect: An Interdisciplinary Exploration. Cambridge, MA: Harvard University Press; 1997.
16. McNair DM, Fisher S, Kahn RJ, Droppleman LF. Drug-personality interaction in intensive outpatient treatment. Arch Gen Psychiatry. 1970;22:128-135.
17. Freud S. A case of hysteria. The Standard Edition of the Complete Psychological Works of Sigmund Freud. Vol 7. London: Hogarth Press; 1905/ 1958.
18. Gibbons FX, Wright RA. Motivational biases in causal attributions of arousal. J Pers Soc Psychol. 1981;40:588-600.
19. Kayatekin MS, Plakun EM. A view from Riggs: treatment resistance and patient authority, Paper X: from acting out to enactment in treatment resistant disorders. J Am Acad Psychoanal Dyn Psychiatry. 2009;37:365-382.
20. Ankarberg P, Falkenström F. Treatment of depression with antidepressants is primarily a psychological treatment. Psychother Theory Res Pract Training. 2008;45:329-339.
21. Mintz D. Meaning and medication in the care of treatment-resistant patients. Am J Psychother. 2002;56:322-337.