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Addressing the Underlying Causes of Treatment Resistance perspective and a proliferation of than they were a quarter of a century stantial y is that as the pendulum has safer, more tolerable, and perhaps ago.1 Treatment resistance remains a swung from a psychodynamic uring the past 2 decades, psy- more effective treatments. Despite serious problem across psychiatric framework to a biological one, the chiatry has benefited from an these advances, however, treatment diagnoses.2 One likely reason that impact of meaning (ie, the role of increasingly evidence-based outcomes are not substantial y bet er outcomes have not improved sub- psychosocial factors in treatment- gests that how the doctor prescribes is actual y more important than what cant, and objectively measurable im- potent than biological effects.4-7,11,13,14 Just as positive transferences to may manifest as treatment resistance. tant from medication typical y pre- conditions, including psychiatric dis- the doctor or drug lead to positive Patients who need their symp- sent as hungry for medications. Al- orders.8,9 And, placebo responses responses, negative transferences are toms to communicate something that though they take the medications produce measur able changes in brain likely to lead to negative responses. they cannot put into words wil be and may report symptom reduction, activity that largely overlap medica- Patients who have been abused or similarly ambivalent.2 When symp- these patients do not function better tion-induced improvements.10 The neglected by caregivers in the past or toms constitute an important defense with pharmacotherapy; in fact, some patient’s desire to change and a posi- those who otherwise feel vulnerable mechanism, patients are also likely seem to get worse. A psychodynamic tive transference to the doctor and to authority figures (either because to resist medication effects until they psychopharmacologist is mindful his or her medications can mobilize of social disadvantage or a propen- have developed more mature defens- that there are countless ways these profound self-healing capacities— sity to acquiesce) are prone to noce- es or more effective ways of coping.3 medications may serve counterthera- capacities that appear to be even bo responses.15,16 The obverse of the Patients who are not resistant to peutic and/or defensive aims.
more potent than the medication’s placebo response, nocebo responses symptom reduction may nonetheless occur when patients expect (either be motivated to resist the doctor on to disavow responsibility for their Although most of our patients ask consciously or unconsciously) to be the basis of a transference experi- feelings and actions.18 This common- us for help, many are conflicted harmed. Many patients who experi- ence of the doctor as untrustworthy ly occurs in the case of primitively about get ing wel if their il ness has ence intolerable adverse effects to or even dangerous. Such patients of- organized and character-disordered created some conscious or uncon- medications are nocebo responders. ten pains takingly negotiate the medi- patients who rely on splitting and scious benefit. If a patient is not It comes as no surprise that these cation, dosing, and timing of medi- projective dynamics. Such patients “ready to change,” it is unlikely that patients are likely to become treat- cations (so as not to feel under the tend to see things strictly in black a medication, however potent, will ment-resistant.
control of the malevolently experi- and white and frequently defend enced doctor) or surreptitiously man- against feeling intolerably and com- man and colleagues11 found, in a Pharmacological treatment age their own regimen (by taking pletely bad by displacing all of placebo-control ed trial, that patients resistance more or less than the prescribed the “badness” onto the “other” in a who received a benzodiazepine for From a psychodynamic perspective, dose). Needless to say, if they are not relationship.
anxiety and who were highly moti- patients may be seen as resistant to taking a therapeutic dose, they lessen vated to change had the most robust medication or resistant from medica- their chances of a therapeutic re- mood stabilizers for bipolar disorder, response. However, placebo recipi- tion. These 2 broad categories of sponse. As noted, if these patients a patient prone to split ing as a de- ents who were highly motivated to pharmacological treatment resis- cannot resist the doctor’s orders, fense wil often experience an imme- change had a greater reduction in tance tend to have different underly- then their bodies may unconsciously diate reduction in dysphoria. A psy- anxiety than patients who took the ing dynamics and may require differ- do the resisting for them, which leads chopharmacologist who is inclined active drug but were less ready to ent kinds of interventions.
(Please see Treatment Resistance, page 24) Patients who are resistant to med- found to be the single most powerful ications have conscious or uncon- determinant of treatment effective- scious factors that interfere with the ness—even more potent than type of desired effect of medications. Often, In 1912, Freud12 noted that the un- form of nonadherence but also in- objectionable positive transference cludes patients who repeatedly expe- (consisting of such things as the pa- rience adverse responses to medica- tient’s belief in the doctor’s salutary tions (ie, nocebo responders).
to get bet er, and the desire to win the tant from medications more typical y doctor’s love or esteem by genuinely are eager to receive the medication trying to get bet er) was a key factor or some benefit that the patient as- in the patient’s ability to overcome cribes to the medication. For such symptoms. This unobjectionable patients, pil s may appear to relieve positive transference, ie, the thera- symptoms, but they do not contribute peutic alliance, is one of the most to an improvement in the patient’s potent ingredients of treatment.12,13 In quality of life. Resistance to med- a large, placebo-controlled, multi- ications and resistance from medi- center trial of treatments of depres- cations are not mutual y exclusive, sion, Krup nick and colleagues14 and some patients present with both showed that patients were most like- dynamics.
active drug and had a strong thera- psychodynamic concept of resis- peutic al iance. Those least likely to tance and concluded that many pa- respond when given placebo had a tients were unconsciously reluctant poor therapeutic alliance. Patients to relinquish their symptoms or were who received placebo and who had a unwit ingly driven, for transference strong treatment al iance had a sig- reasons, to resist the doctor. These nificantly more robust therapeutic same dynamics may apply in phar- response than patients who received macotherapy. Although suffering an antidepressant but had a poor greatly, patients may find good uses therapeutic al iance. Taken together, for their symptoms. Patients who de- these studies examining the relative rive significant secondary gains from effectiveness of biological y and sym- their symptoms (eg, they are relieved bolical y active aspects of the medi- from various burdens, or they re- cation suggest that meaning effects ceive care rather than neglect as a in psychopharmacology are more result of their illness) can be deeply uses of medications (resistance potential sources of resistance to the understand complex situations that Continued from page 23
medication or the doctor are under- more than anything else lends its par- • Identify and contain countertrans- stood, they must be addressed. If they ticular power to our discipline and are clear at the outset, they must be gives us skil s for working with par- addressed preemptively. In this way, ticularly troubled patients.
reduction in dysphoria may be oc- chodynamic psychopharmacologist an al iance is made with the patient curring not because of the medica- recognizes that a rigid mind-body before massive resistance is sparked. Dr Mintz is Director of Psychiatric Education at tion but because it al ows the patient dualism is a fantasy. Experiences, Negative transferences must be iden- the Austen Riggs Center in Stockbridge, Mass. to create a stable split within which feelings, ideas, and relationships tified and worked through. Empathic The author reports no conflicts of in terest he can remain good while al badness change the structure and function of interpretation of nocebo responses concerning the subject matter of this article. the brain just as the state of the brain can resolve adverse effects.21 References
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they address problems at the level of Drug-personality interaction in intensive outpatient what to prescribe; instead, it helps of symptoms. Identify potential mean ing. Psychiatric care providers treatment. Arch Gen Psychiatry. 1970;22:128-135.
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20. Ankarberg P, Falkenström F. Treatment of depres-
• Attend to the patient’s ambiva- may be colored by the doctor’s frus- healthy and effective use of medica- sion with antidepressants is primarily a psychologi- tration and is more likely to produce tions. We should not neglect psycho- cal treatment. Psychother Theory Res Pract Training. • Address negative transferences a negative response.) dynamic contributions that enhance 21. Mintz D. Meaning and medication in the care of
the integration of meaning and biol- treatment-resistant patients. Am J Psychother. • Be aware of countertherapeutic and resistance to medications. Once ogy. It is the capacity to integrate and

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