Activity OverviewIn this activity, faculty will introduce a patient with probableschizophrenia. As the details of the case unfold, participants p p pwill explore options for the treatment of the first episode ofschizophrenia, including the potential role for long-actinginjectables.

Target Audience

This activity is intended for psychiatrists.

Accreditation / Designation Statements

Med-IQ is accredited by the Accreditation Council forMed IQ is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Med-IQ designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Disclosure PolicyMed-IQ requires any person in a position to control the content of an educational activity to disclose all relevant financial relationships with any commercial interest Thefinancial 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 will not be permitted to contribute to this CME activity in any way. Med-IQ has policies in place that will identify and resolve COIs prior to this educational activity Med-IQ alsoresolve COIs prior to this educational activity. 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.

Disclosure Statement

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

John Lauriello, MD, has indicated no real or apparent conflicts.

Disclosure Statements

The activity planners and peer reviewers have no financial relationships to disclose.

Acknowledgment of Commercial Support

This activity is supported by an educational grant from Otsuka America Pharmaceutical, Inc.

Copyrightpy g© 2014 Med-IQ®. All rights reserved.

Medium & Method of ParticipationTo receive credit, read the introductory CME material, watch the Webcast, and complete the evaluation, attestation, and post-test, answering at least 70% of the post-test questions correctly. g p q y

The evaluation, attestation, and post-test will be accessible by clicking the “Get Credit” tab at the bottom of the Webcast at the conclusion of the activity.

Contact InformationCall toll-free 866 858 7434E-mail info@med-iq.com

Please visit us online at www.Med-IQ.com for additional activities sponsored by Med-IQ.

Sara C. Miller, MSAssistant Director, Educational Strategy and Content

Activity Planners

Assistant Director, Educational Strategy and ContentMed-IQBaltimore, MD

Amy SisonDirector of Continuing Medical EducationMed-IQBaltimore, MD

John Lauriello, MD

Professor and Chairman

Faculty

Professor and Chairman

Chancellor’s Chair of Excellence in Psychiatry

University of Missouri Department of Psychiatry

Columbia, MO

Upon completion, participants should be able to:

• Outline the misconceptions of LAI antipsychotic

Learning Objectives

• Outline the misconceptions of LAI antipsychotic medications for the treatment of schizophrenia

• Examine the potential role of LAI antipsychotic medications for the treatment of first-episode schizophrenia

Joe • Joe is a 20-year-old male sophomore at a large

state university

• He did well his freshman year, although he received an underage drinking citation at a fraternity party

• In his sophomore year, Joe joined a fraternity, one that was known for having a largenumber of parties and heavymarijuana use

• Several months into thesemester, Joe was arrested by campus police for “disorderly behavior”

Joe Gets Arrested

• At the time of his arrest, Joe d t b “hi h” dappeared to be “high” and

was disoriented, combative, and resisted the police

• Brought to the local ED

• Thinking remained disturbed after several hours ofafter several hours of observation

• Admitted to the psychiatric unit on an involuntary hold

Cannabis and Psychosis

• Prevalence of cannabis noted to be as high as 43% in patients with schizophreniaas 43% in patients with schizophrenia

• Associated with earlier onset of psychosis

• Predicts onset of psychosis independent of intoxication effects and other confounding effects

U i d l i th lik lih d f• Use in adolescence increases the likelihood of experiencing symptoms of schizophrenia in adulthood

Donoghue K, et al. Psychiatry Res. 2014;215:528-32; Di Forti M, et al. Schizophr Bull. 2014 [epub ahead of print]; Bersani G, et al. Psychopathology. 2002;35:289-95; Stefanis NC, et al. Addiction. 2004;99:1333-41.

Joe Goes to the Hospital

• In the psychiatric hospital, Joe is now calmer but tells the psychiatrist he knows the other fraternity members arepsychiatrist he knows the other fraternity members are “spiking” his drink and “messing with his stuff”

• Says he can hear them through his bedroom walls

• Believes others arejealous because he is better than they areis better than they are

Joe’s Diagnosisg• The treatment team discussed Joe’s diagnosis and

considered several possibilities, including:

– Substance-induced psychotic disorder

– Substance intoxication

– Schizophreniform disorder

– Bipolar disorderp• Joe is given a diagnosis of substance-induced psychotic

disorder • Treatment team is concerned that these may be the first

signs of schizophrenia

Joe Starts Medicine

• The treatment staff called Joe’s parents who were surprised that he was in a psychiatric hospitalp p y p

• They said he seemed fine, although his phone calls had become shorter and less frequent

• They reported that Joe’s fraternal uncle was diagnosed with schizophrenia

• The team started him on a low-dose, second-generationsecond generationantipsychotic

• Joe seemed to respondwell to the medication

APA20041

TMAP20062

PORT20093

Guideline / Algorithm Recommendations

First episode SGA SGA SGA, FGA

Second choice SGA, FGA, C SGA, FGA SGA, FGA

Third choice C C C

Fourth choice (C+) C+ –

Fifth choice – FGA or SGA –

Combinations – C + SGA + FGA + ECT +

MS

–

MS

FGA: first-generation antipsychotic SGA: second-generation (atypical) antipsychotic C: clozapine C+: clozapine augmentation with FGA,SGA or ECTMS: mood stabilizer 1. APA. Practice Guideline for the Treatment of

Patients With Schizophrenia, 2e. 2004;2. Moore T, et al. J Clin Psychiatry. 2007;68:1751-62;

3. Kreyenbuhl J, et al. Schizophr Bull. 2010;36:94-103.

Schizophrenia PORT RecommendationsPsychopharmacologic Treatment

Treatment of acute • First-line treatment with an antipsychotic other than positive symptoms (acute exacerbation) in treatment-responsive schizophrenia

clozapine• Treatment trials at least 2 weeks, with an upper limit

of 6 weeks to observe optimal response• Antipsychotic choice: consider individual preference;

prior treatment response; experience with side effects; adherence history; relevant medical history and risk factors; medication side-effect profile; long-term treatment planning

Treatment of acute • Antipsychotic treatment other than clozapine and

Buchanan R, et al. Schizophr Bull. 2010;36:71-93.

positive symptoms in first-episode schizophrenia

olanzapine• Starting antipsychotic doses should be lower than

those recommended for patients with multiple episodes

Drug Formulation (Approval) Dose Range

Aripiprazole (Abilify®) Oral (2002) 10-30 mg/day

Aripiprazole (Abilify Maintena®) Long-acting IM (2013) 300-400 mg IM/month

A i l (S h i ®) O l bli l (2009) 10 i d il

Atypical Antipsychotics for Schizophrenia

Asenapine maleates (Saphris®) Oral – sublingual (2009) 5-10 mg twice daily

Clozapine (Clozaril®) Oral (1989) 300-900 mg/day

Lurasidone HCl (Latuda®) Oral (2010) 40-160 mg/day

Iloperidone (Fanapt®) Oral (2009) 6-12 mg twice daily

Olanzapine (Zyprexa®) Oral (1996) 10-20 mg/day; higher doses are often used if treatment refractory

Olanzapine fumarate (ZyprexaRelprevv®)

Long-acting IM (2009) 150-300 mg IM every 2 weeks

Paliperidone (Invega®) Oral (2006) 6-12 mg/day

Paliperidone palmitate (Invega®

Sustenna®)Long-acting IM (2009) 117-234 mg/month

Quetiapine fumarate (Seroquel ®,Seroquel XR®)

Oral (1997, 2007) 150-800 mg/day; higher doses are often used if treatment refractory

Risperidone (Risperdal®) Oral (1993) 4-16 mg/day

Risperidone (Risperdal® Consta®) Long-acting IM (2003) 25, 37.5, or 50 mg IM every 2 weeks

Ziprasidone (Geodon®) Oral (2001) 80-160 mg/dayTexas DOS Health Services. Texas Medication Algorithm Project Procedural Manual: Schizophrenia Treatment Algorithms. 2008.

FDA. www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm

Factors Associated With the Potential for Positive Clinical and Functional Outcomes

• Low initial severity of positive and negative symptoms• Better social and occupational functioningp g• Short duration of untreated psychosis• Insight into their illness• Female sex• More education• Good early response to antipsychotic treatment• Collaborative therapeutic alliance• Supportive family/caregivers• Supportive family/caregivers• Access to comprehensive, coordinated, and continuous treatment• Opportunities to engage in functional activities and receive

specialized interventions• Absence of substance abuse

Henry AD, Coster WJ. Am J Occup Ther. 1996;50:171-81; Ho BC, et al. Am J Psychiatry.1998;155:1196-201; Whitty P, et al. Psychol Med. 2008;38:1141-6;

Spellmann I, et al. Psychiatry Res. 2012;198:378-85; Compton MT, et al. Early Interv Psychiatry. 2014;8:50-8.

Early Responders Show Early and Consistent Improvement–Clinical Outcomes

0

5

n

ER group (n = 144)-5

-10

-15

-20

-25

uar

es M

ean

Ch

ang

e i

AN

SS

To

tal S

core

* * * * *

ER group (n = 144)ENR group (n = 192)

*P < 0.001

Kinon B, et al. Schizophr Res. 2010;118:176-82.ER: early respondersENR: early non-responders

-30

-35

-400 2 4 6 8 10 12 14

Weeks

Lea

st S

qP

A * *

Early Responders Show Early and Consistent Improvement–Functional Outcomes

n

16ER groupENR group* * * *

Sq

uar

es M

ean

Ch

ang

e in

Bas

elin

e to

En

dp

oin

t

*P < 0.0016

4

2

12

10

8

14

*

SOFI: Schizophrenia Objective Functioning InstrumentER: early respondersENR: early non-responders

Overall LivingSituation

InstrumentalActivity

ProductiveActivity

SocialFunctioning

Lea

st S

SO

FI

0

-2

-4

Kinon B, et al. Schizophr Res. 2010;118:176-82.

Majority of First-Episode Patients Achieve Remission in the First Year of Treatment

100 10 weeks

ula

tive

% R

esp

on

din

gto

Tre

atm

ent

60

70

50

40

10 weeks24 weeks1 year2 years

30

80

90

Cu

mu

Lieberman JA, et al. Neuropsychopharmacology. 1996;14:13S-21S.

20

10

00 4 12 20 28 32 40

Weeks in Treatment

6 16 24 36 44 48 52 56 60

Joe Goes Back to School

• At discharge, Joe was instructed to continue his medication and abstain from drugs and alcohol

• One month later, the police were called by Joe’s parents, who were concerned that he was telling them strange things

• The police went to his school to check on him; he refused to let them in

• He was brought to the ED against his will

• In the ED, Joe admitted that he had not been taking his ti h ti di tiantipsychotic medication

• His fraternity brothers said he was keeping to himself and smoking a lot of marijuana

• His urine was positive for cannabinoids

• He was readmitted to the psychiatric hospital

Joe’s Second Hospitalization

• Joe was again started on a second-generation antipsychotic—this time, one that also had an LAIantipsychotic this time, one that also had an LAI formulation, in case this was needed in the future

• The treatment team discussed using an LAI

• Joe and his parents expressed concerns about using an LAI at this time, but would consider it in the future

• Joe stayed in the hospital for 1 week; the university concluded that he was not stable enough to continueconcluded that he was not stable enough to continue enrollment, so it was decided that he would leave school early and live with his parents

Substance Abuse May Increase the Risk of Nonadherence

• Nearly one-half P = 0.014

of patients in a prospective 4-year study (N = 99) were active substance abusers (n = 42)

• Patients who actively No

nad

her

ent,

%

34

47

67

20

40

60

80

Patients who actively abused substances were significantly more likely to be nonadherent

N

0

20

No PastHistory

PastHistory

CurrentUser

Hunt GE, et al. Schizophr Res. 2002;54:253-64.

Cannabis Use Significantly Increases the Risk of Medication Nonadherence in Patients

With First-Episode Schizophrenia

2 50No cannabis useCannabis use

HR (95% CI): 2.4 (1.5-3.9)P < 0.001

azar

d E

stim

ate

of

No

nad

her

ence

2.50

2.00

1.50

1.00

Ha N

0 5 10 15Months

0.50

0.00

Miller R, et al. Schizophr Res. 2009;113:138-44.

LAI Antipsychotics:Myths and Realities

• Myth: “Most patients have an unfavorable view of LAIs and won’t take them, so discussing them as a treatment option , g ponly risks harming the clinical relationship”– Reality: Informing patients of their options and the associated

risks and benefits allows for shared decision making, provides an opportunity for patient preferences to be considered, and lessens the sense of coercion

• Myth: “Research fails to demonstrate the superiority of LAIs over oral antipsychotics in preventing relapse so there is noover oral antipsychotics in preventing relapse, so there is no point in prescribing them”– Reality: Results from randomized clinical trials and community-

based studies are often mixed, but results from observational studies do find advantages to LAIs in adherence and relapse outcomes

Jaeger M, et al. Psychiatry Res. 2010;175:58-62; Adams CE, et al. Br J Psychiatry. 2001;179:290-9;Patel MX, et al. Br J Psychiatry Suppl. 2009;52:S1-S4; Patel MX, et al. Adv Psychiatr Treatment. 2005;11:203-10.

LAI Antipsychotics in First-Episode Schizophrenia

• The use of LAI antipsychotics earlier in the disease course may improve outcomescourse may improve outcomes

• Most first-episode patients randomized to LAI antipsychotics (73%) accept the recommendation

• Patients receiving LAIs had greater adherence and lower relapse rates than patients assigned to oral agents

• Nearly two-thirds (64%) of patients achieved remission, and 97% of these maintained remission to the endpointand 97% of these maintained remission to the endpoint

• The early introduction of LAI antipsychotics did not negatively affect adherence attitudes

Emsley R, et al. Int Clin Psychopharmacol. 2008;23(6):325-31; Weiden PJ, et al. J Clin Psychiatry. 2009;70(10):1397-406;Weiden PJ, et al. J Clin Psychiatry. 2012;73(9):1224-33.

Joe Goes Home• With some reluctance, Joe went home with his parents

• With the structure of home, Joe seemed to be

doing well

• Joe started working in his father’s landscaping business with the plan to enroll in the local community college in the fall

• At the end of the summer, Joe began tobehave oddly and refused to go to workor leave his roomor leave his room

• Joe became convinced he was a time traveler

• The family was very concerned andcalled his psychiatrist, Dr. L

Joe’s Relapse• Joe’s parents convinced Joe to go to the psychiatrist

• While there, he repeats his belief that he is a ti t l d j t t t b l ft ltime traveler and just wants to be left alone

• Urine and blood screen for substances are negative

• Dr. L. asks Joe if he has been taking his medication; Joe initially says he has been, but sometimes misses doses

Eventually he admits that he stopped• Eventually, he admits that he stopped taking it several months ago because it was a hassle to take pills every day,made him feel weird, and he didn’t think he needed it anymore

What to do Next for Joe?

• The psychiatrist asks Joe’s parents to join Joe to determine what to do nextdetermine what to do next

• Joe’s parents are distraught because they thought he had been taking his pills

• Joe reiterates that he didn’t feel like he needed them and they were a pain to take

If Joe were your patient, how would you plan thehow would you plan the next stage of his treatment?

Please go to Webisode #2 for the continuation offor the continuation of Joe’s story

To receive credit, click the “Get Credit” tab at the bottom of the Webcast for access to the evaluation,

attestation, and post-test.

© 2014

Content is being used for illustrative purposes only and any person depicted is a model.