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
While patients may feel better, influences experience. A psychody-
1. Kessler RC, Berglund P, Demler O, et al; National
they actually do worse. No longer namic psychopharmacologist con- uses of medications (resistance fromComorbidity Survey Replication. The epidemiology of
feeling personally responsible for siders that a positive or negative medications). Countertherapeutic major depressive disorder: results from the National
Comorbidity Survey Replication (NCS-R). JAMA.
symptomatic behavior, they give medication response may be a direct uses of medications should also be 2003;289:3095-3105.
their worst instincts free rein, exacer- action of the pil or may be mediated interpreted. As a prescriber, you 2. Plakun EM. A view from Riggs—treatment resis-
tance and patient authority: I. A psychodynamic per-
bating personal and interpersonal by the meanings the patient at aches might tolerate some irrational use of spective. J Am Acad Psychoanal Dyn Psychiatry.
chaos. It is important not to col ude to the pil .
medications if the patient is working 2006;34:349-366.
Mind-body integration also means through an issue that interferes with 3. Mintz D, Belnap B. A view from Riggs: treatment
resistance and patient authority—I I. What is psy-
petent patients whose treatment re- that psychotherapy and psychophar- a healthier use of those medications. chodynamic psychopharmacology? An approach to
sistance relates to defensive use of macology wil need to be wel -inte- There comes a time, however, when pharmacologic treatment resistance. J Am Acad Psy-choanal Dyn Psychiatry. 2006;34:581-601.
medications. Rather, it is crucial to grated so that psychopharmacologi- discontinuation of a counterthera- 4. McKay KM, Imel ZE, Wampold BE. Psychiatrist ef-
empathical y help them understand cal interventions facilitate the psy- peutic medication may become a fects in the psychopharmacological treatment of
depression. J Affect Disord. 2006;92:287-290.
that although they are il , they remain chotherapy and so that the therapy condition of continued pharmaco- 5. Kirsch I, Sapirstein G. Listening to Prozac but hear-
helps the patient become conscious logical treatment.
ing placebo: a meta-analysis of antidepressant
Medications can be used defen- of psychological sources of pharma-
medication. June 26, 1998. http://psycnet.apa.
sively in myriad ways. Patients who cological treatment resistance. Ef- transference in prescribing. When 37220.127.116.11a. Accessed June 24, 2009.
experience people as dangerous and fective psychopharmacological in- patients struggle with overwhelming 6. Khan A, Warner HA, Brown WA. Symptom reduc-
tion and suicide risk in patients treated with placebo
unreliable may attempt to replace terventions to treatment nonresponse dysphoric affects, they often evoke in antidepressant clinical trials: an analysis of the
people with pil s. Stil other patients might include an increase in frequen- corresponding effects in their pre- Food and Drug Administration database. Arch Gen
may feel that any “negative” feeling cy of appointments rather than an scribers.2 It seems likely that a medi- 7. Kirsch I, Moore TJ, Scoboria A, Nichols SS. The
is pathological and should be extin- increase in medication dosage.20
cation regimen made up of, for ex- emperor’s new drugs: an analysis of antidepressant
medication data submitted to the U.S. Food and Drug
Sir Wil iam ample, 3 antidepressants, 4 mood Administration. Prevention & Treatment 5, Article 23.
this can lead a well-meaning psy- Osler, the father of modern medi- stabilizers, 3 antipsychotics, and 1 or 2002. http://www.journals.apa.org/prevention/
chiatrist toward an ever more com- cine, remarked that “it is much more 2 anxiolytics, has in part been shaped volume5/pre0050023a.html. 8. Brody H. Placebos and the Philosophy of Medicine.
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regimen that actually contravenes tient has a disease than to know what men is unlikely to be effective and is 9. Moerman DE, Jonas WB. Deconstructing the pla-
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sort of disease a patient has.” This is perhaps aimed at treating the doc- Intern Med. 2002;136:471-476.
When pil s are used to manage de- a central tenet of psychodynamic tor’s anxiety rather than the patient’s; 10. Mayberg HS, Silva JA, Brannan SK, et al. The
functional neuroanatomy of the placebo effect. Am J
velopmental y appropriate feelings, psychopharmacology. Practically, the patient is not the only source of Psychiatry. 2002;159:728-737.
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sadness, frustration, or anger, pa- should get a thorough developmental namic psychopharmacologist recog- Stage of Change predicts outcome in a panic disor-
der medication trial. Anxiety. 1994;1:64-69.
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assumptions in identifying evidence-based treat-
so directly assess the patient’s at i- sultation about difficult cases helps ments in mental health. Clin Psychol Rev. 2005;25:
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role of therapeutic al iance in psychotherapy and
“turned into a zombie,” and so on). Conclusion
pharmacotherapy outcome: findings in the National
Psychodynamic psychopharmacol- This not only helps assess potential There are many sources of pharma- Institute of Mental Health Treatment of Depression
Col aborative Research Program. J Consult Clin Psy-
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Psycho dy namic psychopharmacol- may enhance the al iance.
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• 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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