4 Secrets of Successful Pharmacotherapy

Words to the wise: 4 secrets of successful pharmacotherapy

Put to good use the placebo eﬀ ect, conditioned responses, and the power of suggestion

® Dowden Health Media ny medication’s therapeutic success depends on the interaction between its specifi c biochemical A effects and nonspecifiCopyright c factors.For1 Thus, personal clinical use only trial designers may view the placebo effect as undesir- able, but it can be a valuable response that improves treatment outcomes in clinical practice. As Freud stat- ed, “Expectation colored by hope and faith is an effec- tive force with which we have to reckon … in all our attempts at treatment and cure.”2 This article describes how experienced clinicians make use of the placebo effect and 3 other powerful, nonspecifi c elements of successful pharmacotherapy. VEER

The placebo eﬀ ect 2008 © The placebo effect is any effect attributable to a pill or potion that does not originate from its specifi c pharma- Moshe S. Torem, MD, DFAPA cologic properties.3 Its clinical value has been trivialized, Chief, Integrative medicine Akron General Medical Center in part because of misconceptions (Table 1, page 20). For Medical director, Center for Mind-Body Medicine example, the placebo effect is commonly believed to be Professor of psychiatry short-lived, whereas in fact it can last a long time.4 Northeast Ohio Universities College of Medicine Rootstown, OH In clinical practice, our goal is to enhance the placebo effect to maximize a desirable therapeutic outcome (Table 2, page 20).5 Therefore, before I prescribe a medication, I tell my patient that I have selected a particular medication because I have had good results with it in many other patients and I believe it will work well for him or her, too. Too often, doctors feel pessimistic about a medication’s potential therapeutic result and communicate Current Psychiatry this pessimism. What the patient hears is, “There’s Vol. 7, No. 12 19

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19_CPSY1208 19 11/14/08 8:40:39 AM Table 1 Correcting misconceptions about the placebo eff ect Misconception What the evidence shows

Placebo effects are short-lived The placebo effect has been documented to last for a long time

Only complaints that are psychologically Changes after placebo have been documented 4 secrets of originated respond to placebo for most symptoms, including those originating from pharmacotherapy somatic diseases Placebo responders are distinctly There is no difference between placebo responders different from nonresponders and nonresponders

The placebo effect is only about The placebo effect can be up to 100% of the total one-third of the total therapeutic effect therapeutic effect

Only about one-third of the The placebo response is context-dependent population responds to placebo and may include >90% of the patient population Clinical Point Source: Reference 4 Experienced Table 2 gest that he be treated with cognitive-be- clinicians understand Clinical strategies to enhance havioral therapy (CBT) and mirtazapine. the placebo eff ect’s the placebo eff ect I tell Mr. B this antidepressant has excel- power and harness lent potential to help him recover from de- • Develop a sustained therapeutic partnership pression. I also inform him that improved it to benefi t their with the patient patients sleep and appetite may be the fi rst eff ects he • Listen effectively and verify that the patient experiences. I give Mr. B an appointment for 1 feels listened to week later, and when he comes in he reports • Provide comprehensible explanations improved sleep and appetite, as expected. of health problems therapeutically tailored for each patient’s needs and personality style Even though studies of antidepressants • Show empathy, care, and concern for the rarely show mood improvements within patient as a person the fi rst 7 days, it is not unusual to hear pa- • Enhance patients’ sense of control tients report feeling less depressed within and mastery over their predicament days after they start a new antidepressant. Source: Reference 5 Although the drug’s specifi c chemical effects on the brain may not be suffi cient to nothing else I can do for you; why not explain this phenomenon, the explanation try this medication, even though I don’t probably lies in nonspecifi c effects—such as believe it’s going to work.” This may cre- the patient expecting that this medication ate a negative placebo effect6—termed the will make him feel better. “nocebo” effect—which gives the patient a The placebo effect can occur as soon as negative expectation about the treatment’s a patient starts a medication. Experienced outcome. The patient internalizes the doc- clinicians understand the placebo effect’s tor’s words and lives out this negative ex- power and harness it to benefi t their pectation. patients.

CASE REPORT Predicting positive results Conditioned responses Mr. B, age 42, has a history of recurrent de- Many biological responses can be associ- pression associated with severe insomnia, ated with visual, auditory, tactile, olfac- poor appetite, signiﬁ cant weight loss, and tory, or gustatory stimuli. Nonconditioned psychosocial withdrawal with feelings of physiologic responses paired with condi- hopelessness. After I take a detailed history tioned stimuli induce the same biological Current Psychiatry 20 December 2008 and do a mental status examination, I sug- effects of a drug. Evidence supporting this

20_CPSY1208 20 11/14/08 8:40:46 AM phenomenon includes successful condition- Often patients come to my offi ce feeling ing of the immune system.7-10 Conditioned thirsty. My staff or I offer them a glass of responses—as demonstrated in glycemia water or a cup of tea. As patients sip from regulation10 and with psychopharmacolo- the cup, they swallow and incorporate the gy11—also can enhance the desirable results liquid into their bodies. At the same time, I of pharmacotherapy. use verbal interventions to make them feel listened to and understood. They internal- CASE REPORT ize this emotional experience in connection A soothing drink with swallowing the liquid. Ms. L, a 22-year-old college student, suff ers Later, when swallowing the new medi- from obsessive-compulsive disorder associ- cation as instructed, the patient re-experi- ated with anxiety and depression. She arrives at ences the positive therapeutic effect that the appointment hurried and worried that she was internalized in the doctor’s offi ce. might be late. She is short of breath and looks stressed. The nurse off ers Ms. L a cup of tea or water. She chooses a glass of water and is asked The power of suggestion to bring it into her session. The power of suggestion has been shown Clinical Point Following a comprehensive interview and to positively or negatively affect treatment Learn to wisely use mental status examination, I recommend CBT 12,13 outcomes. In practice, most clinicians the power of your plus medication. Considering Ms. L’s medica- give unintentional suggestions by how and tion history, we agree to start treatment with what they communicate to the patient. words and body sertraline. We review its potential benefi ts and We make predictions about the patient’s language to enhance expectations that it will reduce her anxiety, al- disease in terms of progress, severity of the positive outcome leviate her ruminating obsessive worries, and symptoms, and expected treatment out- of pharmacotherapy improve her mood. I give her a 50-mg sample comes, including possible side effects. The and inform her that some patients experience patient consciously and subconsciously positive eff ects soon after taking the medica- internalizes these predictions, and then ex- tion. I then ask her to take the fi rst pill, using her hibits the outcome predicted by the medical glass of water. She does so and thanks me for expert. This is compatible with Watzlawick’s being attentive to her needs. principle14 that the prediction of an event I instruct her to call within 1 week and report may lead to events fulfi lling the prediction. on her condition, even if she feels better. Seven In clinical practice, be aware of the power in days later she reports that she is feeling better your words and body language and learn to and is looking forward to her next appoint- use them wisely to enhance the positive out- ment. She reports no side eff ects. come of pharmacotherapy. continued Read today’s psychiatric news on CurrentPsychiatry.com

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21_CPSY1208 21 11/14/08 8:40:50 AM Box Using suggestion to reframe initial side eff ects as positive signs

s. M, age 32 and single, has an anxiety Discussion. In pharmacotherapy, side effects Mdisorder associated with bipolar may appear before patients experience a depression. She has discontinued several medication’s benefi cial/therapeutic effects. psychotropics because of uncomfortable side Patients’ initial experience often determines 4 secrets of effects, such as constipation. whether or not they will continue taking a pharmacotherapy After taking a detailed history, I decide prescribed medication. I know Ms. M may to prescribe quetiapine. I tell Ms. M about stop taking quetiapine—as she has done this medication’s potential benefi ts and side with other medications—if she initially has effects. One common side effect is dry mouth, uncomfortable side effects. which often occurs before patients experience Instructing patients to expect a specifi c therapeutic effects. side effect (such as a dry mouth with I inform Ms. M that a dry mouth will be her quetiapine) and associating it with a future sign that the medication has begun to work, therapeutic benefi t sets up a road map of and benefi cial effects—such as improved expectations. They know their experience is Clinical Point sleep, reduced anxiety, and improved compatible with the doctor’s predictions. For Reframing a side mood—will soon follow. I then instruct Ms. M, I reframed the side effect as a positive her to call my offi ce and report when she sign that recovery has begun, with more eff ect as a sign that experiences a dry mouth. positive changes to come. recovery has begun sets up a road map of expectations, CASE REPORT This vignette illustrates the importance of Predicting improvement with more positive suggesting to the patient a positive out- Mrs. J, age 48, has had dysthymic disorder and come of pharmacotherapy associated with changes to come fi bromyalgia for many years. She describes a particular action (calling the doctor’s how various specialists have tried to alleviate offi ce to report results). When the patient her depression and chronic pain. Follow-up promised to call, she internalized the sug- questions reveal that whenever she received a gestion that calling would be associated new prescription the physician would alert her with feeling better—and that is what hap- to all the possible side eff ects and instruct her pened. This intervention contrasts with to call the offi ce if she developed a problem saying to the patient, “Call me if you have with the new medication. a problem with any of these side effects,” Invariably, Mrs. J would call as instructed which gives the patient a suggestion to call and describe side eff ects she developed with and report a problem. the new medication. Often the doctor would The suggestion effect also can be used to discontinue the medication, depriving Mrs. J reframe a predictable side effect as a posi- of benefi ts she might have derived later. tive sign that indicates the beginning of My approach is diff erent. Although I an- change leading to recovery (Box). swer all her questions about potential side eff ects, I also emphasize this prescription’s potential benefi ts such as improved sleep, Participatory pharmacotherapy appetite, thoughts, and mood. I tell her she Many patients seek ownership in making may experience improved sleep before im- decisions about their treatment and medi- proved mood. I then make the following re- cations. In participatory pharmacotherapy, quest: “Mrs. J, will you please promise to call patients provide you with data and valu- me by Tuesday next week even if you begin able information—such as family history, to feel better?” personal medical history, and experience When Mrs. J calls to report on her status, with treatment—and inform you about she mentions that she is sleeping better and which medications worked best and which has begun to feel better during the day. She did not work. You invite patients to predict says that her husband told her she has started how they see themselves getting better and Current Psychiatry 22 December 2008 to smile again. into recovery.

22_CPSY1208 22 11/14/08 8:40:56 AM Table 3 Choosing patients for participatory pharmacotherapy Good candidates Exclusionary qualities

Adults Children, adolescents, and prison inmates

No history of alcoholism or drug Alcohol dependence or drug addiction addiction

Average and above intelligence Below-average intelligence

Intact cognitive function Cognitive defi cits, such as dementia

Not psychotic Actively psychotic

Good comprehension of diagnosis Poor comprehension of diagnosis and treatment and treatment

Therapeutic alliance is present Therapeutic alliance is absent

Personality style or disorder with a need Passive, dependent personality style or disorder; to be in control of treatment, such as these patients may view a participatory approach Clinical Point obsessive-compulsive personality as the doctor’s lack of confi dence Whenever possible, choose medications Based on this information and your ticipatory pharmacotherapy to enhance knowledge, training, and experience, treatment. the patient you and the patient create a treatment associates with a plan that includes pharmacotherapy tai- CASE REPORT positive experience, All in the family lored to the patient’s specifi c needs. The based on family and following case illustrates the use of par- Mr. A, age 28 and single, has been diagnosed personal history Your search is over! DISCOVER CURRENT PSYCHIATRY’S

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23_CPSY1208 23 11/17/08 2:32:37 PM • the best possible outcome with phar- Related Resources macotherapy. • Brody H. The placebo response: how you can release the body’s Not all patients are candidates for par- inner pharmacy for better health. New York, NY: HarperCollins Publishers; 2000. ticipatory pharmacotherapy (Table 3, page • Spiro H. The power of hope: a doctor’s perspective. New 23), but many respond well to it. One key is Haven, CT: Yale University Press; 1998. to avoid medications the patient has expe- • Ernst E. Placebo: new insights into an old enigma. Drug rienced as unhelpful, ineffective, or associ- Discov Today 2007;12:413-8. 4 secrets of ated with side effects. Whenever possible, Drug Brand Names pharmacotherapy choose medications the patient associates Lithium • Eskalith, Lithobid Quetiapine • Seroquel Mirtazapine • Remeron Sertraline • Zoloft with a positive experience or expectation, Disclosure based on family and personal history. Dr. Torem reports no fi nancial relationship with any company In patients with a defi ant-oppositional whose products are mentioned in this article or with personality, consider framing the treat- manufacturers of competing products. ment decision as a choice between 2 equal- ly effi cacious medications. This gives the patient the sense of control in choosing his Clinical Point with a bipolar mood disorder. As part of a de- or her own medication, which is jointly Not all patients tailed family history, he reports that his ma- monitored. ternal grandfather, mother, and a maternal are candidates uncle were diagnosed with mood swings and References 1. Frank JD, Frank JB. Persuasion and healing. Baltimore, MD: The for participatory were successfully treated with medications, Johns Hopkins University Press; 1991. specifi cally lithium. He states that he believes 2. Freud S. The complete psychological works of Sigmund Freud. pharmacotherapy, Strachey J, trans-ed. Toronto, Ontario, Canada: Hogarth Press; but many respond he has the same condition. 1953. I compliment Mr. A for being so well in- 3. Wolf S. The pharmacology of placebos. Pharmacol Rev well to it 1959;11:689-704. formed about his grandfather and uncle and 4. Ernst E. Placebo: new insights into an old enigma. Drug Discov Today 2007;12:413-8. educate him about mood stabilizers’ benefi ts 5. Brody H. The placebo response: recent research and in bipolar disorder. I tell him about the fi nd- implications for family medicine. J Fam Pract 2000;49:649-54. 6. Spiegel H. Nocebo, the power of suggestibility. Prev Med 1997; ing that if lithium has helped his relatives, it 26:616-21. will probably help him as well. 7. Ader R, Cohen N. Behaviorally conditioned immuno- suppression and murine systemic lupus erythematosus. I also reassure Mr. A that, in deciding what Science 1982;215:1534-6. 8. Ader R. The role of conditioning in pharmacotherapy. In: medications to avoid and what medications Harrington A, ed. The placebo effect: an interdisciplinary exploration. to use, I will consider his experience with spe- Cambridge, MA: Harvard University Press; 1997:138-65. 9. Olness K, Ader R. Conditioning as an adjunct in the cifi c antidepressants that did not help him. pharmacotherapy of lupus erythematosus. J Dev Behav Pediatr He thanks me for considering his suggestion 1992;13:124-5. 10. Stockhorst U, Mahl N, Krueger M, et al. Classical conditioning about what medication to use for him. and conditionability of insulin and glucose effect in healthy humans. Physiol Behav 2004;81:375-88. 11. Wolf S. Effect of suggestion and conditioning on the action Inviting patients to be partners in diagnos- of chemical agents in human subjects—the pharmacology of placebos. J Clin Invest 1950;29:100-9. ing their illnesses and formulating treat- 12. Lown B. The verbal conditioning of angina pectoris during ment plans improves the likelihood of: exercise testing. Am J Cardiol 1977;40:630-4. 13. Lown B. Introduction. In: Cousins N. The healing heart. New • a successful therapeutic alliance York, NY: W.W. Norton; 1983:11-28. • adherence with prescribed medica- 14. Watzlawick P. If you desire to see, learn how to act. In: Nardone G, Watzlawick P, eds. The art of change. San Francisco, tions CA: Jossey-Bass; 1993:1-16. Bottom Line Nonspecifi c ingredients of treatment—such as placebo eff ects, conditioning eff ects, and suggestion eff ects—can improve pharmacotherapy results. When prescribing medications, consider utilizing these eff ects by conveying hope, optimism, and realistic confi dence in a desirable therapeutic outcome. The result is often greater Current Psychiatry 24 December 2008 therapeutic eff ectiveness with fewer side eff ects.

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