Activity Overview In this activity, faculty will introduce a patient with probable schizophrenia. As the details of the case unfold, participants p will explore options for the treatment of the first episode of schizophrenia, including the potential role for long-acting injectables. Target Audience This activity is intended for psychiatrists.
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Disclosure Statement The content of this activity has been peer reviewed and has been approved for compliance. The faculty and contributors have 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. Disclosure Statements John Lauriello, MD, has indicated no real or apparent conflicts. 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. Copyright 2014 Med-IQ. All rights reserved. Medium & Method of Participation To 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. 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 Information Call toll-free 866 858 7434 E-mail info@med-iq.com Please visit us online at www.med-iq.com for additional activities sponsored by Med-IQ.
Activity Planners Sara C. Miller, MS Assistant Director, Educational Strategy and Content Med-IQ Baltimore, MD Amy Sison Director of Continuing Medical Education Med-IQ Baltimore, MD
Faculty John Lauriello, MD Professor and Chairman Chancellor s Chair of Excellence in Psychiatry University of Missouri Department of Psychiatry Columbia, MO Learning Objectives Upon completion, participants should be able to: 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 large number of parties and heavy marijuana use Several months into the semester, Joe was arrested by campus police for disorderly behavior Joe Gets Arrested At the time of his arrest, Joe appeared dto be high h and was disoriented, combative, and resisted the police Brought to the local ED Thinking remained disturbed after 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 schizophrenia Associated with earlier onset of psychosis Predicts onset of psychosis independent of intoxication effects and other confounding effects Use in adolescence increases the likelihood lih 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 are spiking his drink and messing with his stuff Says he can hear them through his bedroom walls Believes others are jealous because he is better than they are
Joe s Diagnosis The treatment team discussed Joe s diagnosis and considered several possibilities, including: Substance-induced psychotic disorder Substance intoxication Schizophreniform disorder Bipolar disorder 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 hospital 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-generation antipsychotic Joe seemed to respond well to the medication
Guideline / Algorithm Recommendations APA 2004 1 TMAP 2006 2 PORT 2009 3 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 FGA: first-generation antipsychotic SGA: second-generation (atypical) antipsychotic C: clozapine C+: clozapine augmentation with FGA,SGA or ECT MS: 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 Recommendations Psychopharmacologic Treatment Treatment of acute First-line treatment with an antipsychotic other than positive symptoms clozapine (acute exacerbation) in Treatment trials at least 2 weeks, with an upper limit treatment-responsive of 6 weeks to observe optimal response schizophrenia 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 positive symptoms in olanzapine first-episode Starting antipsychotic doses should be lower than schizophrenia those recommended for patients with multiple episodes Buchanan R, et al. Schizophr Bull. 2010;36:71-93.
Atypical Antipsychotics for Schizophrenia 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 Asenapine maleates (Saphris ) Oral sublingual l (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 (Zyprexa Long-acting IM (2009) 150-300 mg IM every 2 weeks Relprevv ) Paliperidone (Invega ) Oral (2006) 6-12 mg/day Paliperidone palmitate (Invega Sustenna ) Quetiapine fumarate (Seroquel, Seroquel XR ) Long-acting IM (2009) Oral (1997, 2007) 117-234 mg/month 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/day Texas 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 functioning 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 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 n Least Sq uares Mean Change i PA ANSS Total Score 0-5 -10-15 -20-25 -30-35 * * * * * ER group (n = 144) ENR group (n = 192) *P < 0.001-40 0 2 4 6 8 10 12 14 * Weeks ER: early responders ENR: early non-responders Kinon B, et al. Schizophr Res. 2010;118:176-82. Early Responders Show Early and Consistent Improvement Functional Outcomes Least Squares Mean Change in SOFI Baseline to Endpoint 16 14 12 10 8 6 4 2 0-2 -4 * Overall * Living Situation * * * Instrumental Activity Productive Social Activity Functioning ER group ENR group *P < 0.001 SOFI: Schizophrenia Objective Functioning Instrument ER: early responders ENR: early non-responders Kinon B, et al. Schizophr Res. 2010;118:176-82.
Majority of First-Episode Patients Achieve Remission in the First Year of Treatment Cumu ulative % Responding to Treatment 100 90 80 70 60 50 40 30 10 weeks 24 weeks 1 year 2 years 20 10 0 0 4 6 12 16 20 24 28 32 36 40 44 48 52 56 60 Weeks in Treatment Lieberman JA, et al. Neuropsychopharmacology. 1996;14:13S-21S. 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 antipsychotic 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 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 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 80 prospective 4-year 60 study (N = 99) were 47 active substance 40 34 abusers (n = 42) Patients who actively 20 abused substances were significantly 0 No Past Past more likely to be History History nonadherent Nonadherent, % 67 Current User 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 Ha azard Estimate of Nonadherence 250 2.50 2.00 1.50 1.00 0.50 No cannabis use Cannabis use HR (95% CI): 2.4 (1.5-3.9) P < 0.001 0.00 0 5 10 15 Months 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 only 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 no point in prescribing them Reality: Results from randomized clinical trials and communitybased 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 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 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 to behave oddly and refused to go to work or leave his room Joe became convinced he was a time traveler The family was very concerned and called 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 time 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 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 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 the next stage of his treatment? Please go to Webisode #2 for 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.