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Series OverviewThis complimentary CME/CE activity is designed to ask learners to test their “schizophrenia IQ” by having participants make critical decisions at key points within specially designed patient cases and select what they believe to be the optimal treatment direction based on their own best practices. Faculty commentary will provide feedback on participants’ selections and, as needed, direct them toward the optimal treatment path; the platform also displays all explanations regarding non-optimal response choices so participants can gain understanding of why a particular approach may not be the best selection. In addition, three “e-briefs” will provide ongoing follow-up with evidence-based best practices and additional faculty tips.

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This activity is intended for hospital-and community-based psychiatrists and psychiatric nurse practitioners.

Target Audience

The College of Physicians and Surgeons of Columbia University is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

The College of Physicians and Surgeons designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Accreditation/Designation Statements

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Privacy and Confidentiality

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For detailed information about our privacy policy, please visit: www.Med-IQ.com/privacypolicy.html.

Disclosure PolicyColumbia University and Med-IQ require any person in a position to control the content of an educational activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines “relevant financial relationships” as those in any amount occurring within the past 12 months, including those of a spouse/life partner, that could create a conflict of interest (COI). Individuals who refuse to disclose are not permitted to contribute to this CME activity in any way. Columbia University and Med-IQ have policies in place that will identify and resolve COIs prior to this educational activity. Columbia University and Med-IQ also requires faculty to disclose discussions of investigational products or unlabeled/unapproved uses of drugs or devices regulated by the US Food and Drug Administration.

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Disclosure StatementThe content of this activity has been peer reviewed and has been approved for compliance. The faculty and contributors have indicated the following financial relationships, which have been resolved through an established COI resolution process, and have stated that these reported relationships will not have any impact on their ability to give an unbiased presentation.

Disclosure StatementsMark Olfson, MD, MPH, has indicated no real or apparent

conflicts.

Peter J. Weiden, MDConsulting fees/advisory boards: Biovail, Bristol-Myers Squibb,

Delpor, Inc., Eli Lilly and Company, Genentech, Lundbeck, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals, VANDA Pharmaceuticals

Contracted research: Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals, Sunovion

Other (Speakers Bureau): Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals, Pfizer, Inc.

None of the employees of Med-IQ or Columbia University CME Office who have worked on this activity have any financial relationships to disclose.

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Statement of Evidence-Based Content

The content and any recommendations, treatments and manners of practicing of medicine in CME activities should be scientifically based, valid and relevant to the practice of medicine. Specifically, (1) all recommendations addressing the medical care of patients must be based on evidence that is scientifically sound and recognized as such within the profession; (2) all scientific research referred to, reported or used in CME in support or justification of a patient care recommendation must conform to generally accepted standards of experimental design, data collection and analysis.

Columbia University and Med-IQ are not liable for any decision made or action taken in reliance upon the information provided through this activity. The cases in this activity have been reviewed and peer approved.

Acknowledgment of Commercial Support

This activity is supported by an educational grant from Janssen Pharmaceuticals, Inc., administered by Janssen Scientific Affairs, LLC.

Copyright© 2011 Columbia University and Med-IQ.

All rights reserved.

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Mark Olfson, MD, MPHProfessor of Clinical Psychiatry

Columbia UniversityResearch Psychiatrist

New York State Psychiatric InstituteNew York, NY

Faculty

Peter J. Weiden, MDDirector

Psychotic Disorders ProgramDepartment of Psychiatry

University of Illinois at ChicagoChicago, IL

Allison Gardner, PhDActivity Planner

Med-IQBaltimore, MD

Learning Objectives• Identify barriers that contribute to patient

nonadherence with therapeutic care plans for schizophrenia

• Describe key elements of the adherence interview to help elicit the best information possible about medication-taking behaviors from patients with schizophrenia

• Develop individualized, recovery-oriented treatment strategies for patients with schizophrenia that incorporate patients’ history and previous adherence challenges

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Case Challenge: Patient History

• JA is a 24-year-old man who emigrated from Asia with his parents 12 years ago

• He did well in high school and had a few close friends

• His parents noticed marked changes in academic performance and behavior once he began college

• His parents report that they've seen him talk to himself and yell out the window at voices; JA has also accused his parents of taping his conversations and unnecessarily calling the police

• He was recently banned from the local mall for a year due to bizarre behavior in front of store mirrors

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Case Challenge: Treatment History

• Following an altercation with another student, JA’s university required that he have a mental health intervention; he unwillingly presents to the clinic

• JA reports smoking marijuana when he first went to college, but no recent history of drug or alcohol abuse

• He was started on oral risperidone titrated up to 4 mg per day

• Treatment relieved some symptoms for the first few months; however, his symptoms have been getting progressively worse

• He has not shown any additional benefit with subsequent antipsychotic dose increases

Treatment Nonadherence in Schizophrenia

• Adherence to antipsychotic therapy is a significant challenge in the management of schizophrenia– Approximately 80% of patients become

nonadherent within 2 years of hospital discharge1

– Definitions and measures of adherence vary widely across studies in this population2

1. Weiden PJ, Olfson M. Schizophr Bull. 1995;21:419-29.2. Velligan DI, et al. J Clin Psychiatry. 2009;70:3-48.

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Relapse

Symptoms Nonadherence

Interaction Between Nonadherence and Symptoms

Weiden PJ, Olfson M. Schizophr Bull. 1995;21:419-29.

Consequences of Nonadherence Are Severe

• ~50% of patients who discontinue/do not take antipsychotics will relapse within 3 to 10 months1,2

• Relapse rates are much higher in nonadherent patients3

– 69% of patients with poor adherence relapsed compared with 18% of patients with good adherence

1. Blackwell B, Clin Pharmacol Therapy. 1972;13:841-8. 2. Hirsch SR, Barnes TRE. In: Hirsch SR, Weinberger DR, eds. Schizophrenia. 1995:443-68.

3. Morken G, et al. BMC Psychiatry. 2008;8:32.

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Partial Adherence and Rate of Rehospitalization

Adapted with permission from Weiden PJ, et al. Psychiatric Serv. 2004;55:886-91.

11-30 > 300

5

10

15

20

25

Maximum Therapy Gap, Days Within 1 Year

Pat

ient

s R

ehos

pita

lized

, %

0 1-10

Detection of Antipsychotic Nonadherence

16

42

58

0

10

20

30

40

50

60

70

Self-report Physician Pill Count

% D

etec

ted

Velligan DI, et al. Psychiatr Serv. 2007;58:1187-92.

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How Does NonadherenceInfluence Outcome?

Indirect effects can be just as damaging

• Incorrect treatment plan when nonadherence is mistaken for efficacy problems OR vice versa

– May result in wrong medication, inadvertent overmedication, or too many medications prescribed

• Viewing adherence as “obedience” can hurt the therapeutic relationship

– Patient afraid of clinician reaction– Clinician frustrated and angry with patient

Velligan DI, et al. J Clin Psychiatry. 2009;70:1-46.

Therapeutic Alliance as a Universal Goal

• Strength of the therapeutic alliance is a universal predictor of good outcome

• Establishing a therapeutic alliance is a common goal of all psychosocial interventions

• The question is: What is the best way to accomplish this goal?

Frank AF, et al. Arch Gen Psychiatry. 1990;47:228-36.

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Case Challenge, Continued

• Although JA does not think he needs medication, his parents assure that he is following his treatment regimen correctly because they watch him take his medication

• He agrees to psychiatric evaluation only due to his parents’ desire and his wish to return to school

Long-Acting Injectable Antipsychotics as an Adherence-Tracking Method

Weiden PJ, et al. Psychiatric Annals. 2011;41:271-8.

Will not immediately change medication attitudes

Performance expectations

Opposition to long-acting injectables usually related to desire to stop all medications

Only accepted if offered to patients adherent to oral medications

Initiation Expect resistance

Current adherence status is unclear

Clinical situationHigh likelihood that patient will stop medication in the near future

Patient is ambivalent about staying on oral medication

May delay, but will not prevent, medication discontinuation; however, enables rapid identification of nonadherence

Emphasize the time-limited trial; patient still controls decision of whether to accept medication

Probable reluctance to report nonadherence

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Barriers to Therapeutic Alliance

• Patient Factors– Communication difficulties – Negative symptoms – Rejection of diagnosis (stigma)– Carrying over negative experiences with other mental

health clinicians

• Clinical Factors– Underestimation of importance of relationship – Conveyed sense of hopelessness– Lack of interest in life goals– Focus on medication at expense of everything else

Velligan DI, et al. J Clin Psychiatry. 2009;70:1-46;Pitschel-Walz G, et al. J Clin Psychiatry. 2006;67:443-52.

Integrating Medication Adherence With a Recovery Orientation

Focus is on helping patient achieve life goals; the dialogue about medication is

centered on how it helps or interferes with goals

Stability is the just the

beginning;aim for

recovery

Expect nonadherence; not “if” but “when”; use the experience

from nonadherence as “learning” not “I told

you so!”

Hopeful stance

includes interest in life

aside from medications

Slide courtesy of P. Weiden, MD

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Case Challenge: Information Gathered on Interview

• On interview, JA’s answers are often difficult to follow and periodically punctuated by laughter

• He describes himself as social, but his parents report he does not currently have any friends

• He eventually reveals that he has been spitting out his medication for the last 2 months after his parents leave the room because he does not think it is needed or helpful

• He asks for this information to not be shared with his parents

Risk Factor Domains for Nonadherence in Schizophrenia

1. Valenstein M, et al. J Clin Psychiatry. 2006;67:1542-50; 2. Olfson M, et al. Psychiatr Serv. 2000;51:216-22; 3. Novak-Grubic V, et al. Eur Psychiatry. 2002;17:148-54; 4. Karow A, et al. J Clin Psychiatry. 2007;68:75-80; 5. Lieberman JA, et al. N Engl J Med. 2005;353:1209-23; 6. Weiden PJ. J Clin Psychiatry. 2007;68:14-9; 7.

Velligan DI, et al. J Psychiatr Pract. 2010;16:34-45; 8. Grunebaum MF, et al. J Clin Psychiatry.2001;62:394-9; 9. Ascher-Svanum H, et al. J Clin Psychiatry. 2006;67:1114-23; 10. Nakonezny PA, et al.

Schizophr Res. 2006;82:107-14; 11. Cabeza IG, et al. Schizophr Res. 2000;41:349-55.

Illness-relatedSubstance abuse comorbidity1,2

Symptom severity1

Lack of insight3Subjective well-being4

Treatment-relatedTolerability5

Antipsychotic efficacy6,7

Regimen complexity8

Therapeutic alliance2

Healthcare-system factors2

Patient-relatedPrevious medication nonadherence9

Demographic characteristics1,10

Subjective response to antipsychotic medications11

Lack of medication supervision8

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Adherence Attitudes and Behavior Are Related but Are Not the Same

Adherence Attitude

Does not wantTakes

WantsTakes

Adherent

Adherence Behavior Favorable Unfavorable

Nonadherent Wants

Does not takeDoes not wantDoes not take

Adapted from Weiden P. J Clin Psychiatry. 2007;68:14-9.

APA Guidelines: Antipsychotic Selection and Medication Adherence

• Antipsychotic medications should be chosen based on the individual patient’s needs

– Past experiences with antipsychotics (history, side effects)

– Patient medication preferences (including route of administration)

• Long-acting injectable antipsychotic medication should be considered for patients with recurring relapses related to nonadherence

Lehman AF, et al; for the Work Group on Schizophrenia. www.psychiatryonline.com/pracGuide/pracGuideChapToc_6.aspx.

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Time to Hospitalization in Patients With “Unstable” Schizophrenia

Rosenheck RA, et al. N Engl J Med. 2011;364:842-51.

Early Intervention With Long-Acting Injectables May Prevent or

Delay Rehospitalization

Adapted from Tiihonen J, et al. Am J Psychiatry. 2011;168:603-9.

Risk of rehospitalization after first hospitalization for schizophrenia

N = 2,588

Haloperidol, depot

Clozapine

Olanzapine

Other antipsychotics

Risperidone, depot

Polypharmacy

Risperidone, oral

Quetiapine

No treatment

Haloperidol, oral

Hazard Ratio With 95% CI0 1 2 3 4

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• Most first-episode patients randomized to long-acting injection (73%) accept the recommendation

• Recommendation delivered as part of a psychoeducational program tailored for first-episode patients and their families

• Caveat is that this estimate does not include first-episode patients who failed to engage in outpatient treatment

Acceptability of Long-Acting Route

Weiden PJ, et al. J Clin Psychiatry. 2009;70:1397-406.

Key Aspects of Successful Psychosocial Interventions

• Understand the patient’s attitudes about medication

– Reasons for adherence/nonadherence• Understand the role of significant others

– Attitudes about adherence – Possible supporting role

• Understand the role of symptoms as a barrier to adherence

• Understand the environmental barriers to adherence

Lehman AF, et al; for the Work Group on Schizophrenia. www.psychiatryonline.com/pracGuide/pracGuideChapToc_6.aspx.

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Therapeutic Approaches:“Medical Model” vs. “CBT” Model

Medical model specific • Discussion of diagnosis and

its implications is essential • Emphasize neurobiologic

basis of symptoms and illness

• Reframe psychotic experiences as illness-based

• Too much interest in personal meaning of symptoms would be colluding

Shared interventions • Avoid blame • Involve families • Stress-vulnerability

important• Relapse prevention

important

CBT model specific • Focus on patient agenda• Emphasis on normalizing • Framing problems from

perspective of patient’s own beliefs

• Interest in the personal meaning of psychotic symptoms

Slide courtesy of P. Weiden, MDCBT = cognitive behavioral therapy.

Medication Adherence: Cognitive Adaptation Training

30

40

50

60

70

80

90

100

3 Months 6 Months 9 Months 12 Months 15 Months

Treatment Period Follow-up

Adh

eren

ce, %

Group- F(2,138) = 23.51; P < 0.0001Interaction with time quadraticF(2,251) = 3.46; P < 0.033U

nann

ounc

ed, I

n-H

ome

Pill

Cou

nts

Velligan DI, et al. Schizophr Bull. 2008;34:483-93.

CAT ▲ PharmCAT ■ TAU ♦N = 95

CAT = cognitive adaptation training;PharmCAT = CAT focused only on medication and appointment adherence;TAU = treatment as usual.

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Matching Interventions to Patient Factors

Key Factor General Clinical Approach Intervention

Unfavorable attitudes to taking or staying on medication

Routinely assessEmphasize alliance

Use patient-centered approachStart with patient’s point of view

Do not confront with disease model of illness, but stay symptom focused

Motivational interviewingCBT

Compliance therapyFamily intervention

NAMI Family-to-Family

Involving significant others influences willingness to take or stay on medication

Include families and significant others in assessments and interviews

Family psychoeducationNAMI Family-to-Family

Role of persistent symptoms interfere with ability to take medications

Consider symptoms as barrier Behavioral interventions (eg, CBT)

Environmental barriers prevent medication access (interacts with persistent symptoms)

Consider treatment environment barriers assuming better symptom control is

currently not possible

ACT/PACT interventionsTransportation

Housing Pharmacy

CAT

ACT/PACT = Program of Assertive Community Treatment; NAMI = National Alliance on Mental Illness. Weiden, P. J Clin Psychiatry. 2007;68:14-9.

Conclusions: Integrating Adherence Into Recovery-Oriented Outpatient Treatment

• Obtaining accurate information about antipsychotic adherence is important to ensure a good therapeutic outcome

• Many risk factors influence nonadherence– Patient-related factors– Illness-related factors– Doctor-patient relationship– Medication regimen

• It is possible to use a recovery-oriented approach to improve medication adherence and subsequent outcomes for outpatients with schizophrenia

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Participate in the Next Case in This Series – Focusing on the Transition From Inpatient to Outpatient Care

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© 2011