8/22/19 1 Long-Acting Injectable Antipsychotics: The Benefits and Barriers Danielle Moses, PharmD, BCPP Psychiatric Clinical Pharmacist SSM Health DePaul Hospital Adjunct Clinical Professor St. Louis College of Pharmacy Disclosure and Conflict of Interest Danielle Moses has no personal or financial conflicts of interest to disclose. Pharmacist Objectives At the conclusion of this program, the pharmacist will be able to: 1. Recognize the appropriateness of long-acting injectable antipsychotic (LAIA) therapy and select the most appropriate LAIA for a specific patient. 2. Describe the benefits of using LAIA therapy for schizophrenia, schizoaffective disorder, and bipolar disorder. 3. Identify barriers to access and use of LAIA therapy and potential strategies to overcome these barriers.
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Long-Acting Injectable Antipsychotics: The Benefits and Barriers
Danielle Moses, PharmD, BCPPPsychiatric Clinical PharmacistSSM Health DePaul HospitalAdjunct Clinical ProfessorSt. Louis College of Pharmacy
Disclosure and Conflict of Interest
Danielle Moses has no personal or financial conflicts of interest to disclose.
Pharmacist Objectives
At the conclusion of this program, the pharmacist will be able to:
1. Recognize the appropriateness of long-acting injectable antipsychotic (LAIA) therapy and select the most appropriate LAIA for a specific patient.
2. Describe the benefits of using LAIA therapy for schizophrenia, schizoaffective disorder, and bipolar disorder.
3. Identify barriers to access and use of LAIA therapy and potential strategies to overcome these barriers.
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FDA approvals Bipolar I D/O Schizoaffective D/O Schizophrenia
Aripiprazole extended release (Abilify Maintena®) X X
Aripiprazole lauroxil (Aristada®) X
Fluphenazine decanoate (Prolixin D®) X
Haloperidol decanoate (Haldol Decanoate®) X
Olanzapine pamoate (Zyprexa Relprevv®) X
Paliperidone palmitate (Invega Sustenna®, Invega
Trinza®)X1 X
Risperidone (Risperdal Consta®, Perseris®) X2 X
1Invega Sustenna only2Risperdal Consta only
Current Practice• USA: 13-38%§ Austria, UK, East Asia, Turkey, and Portugal: 30-50%
• Typical LAIA patient§ Severely and persistently ill§ Multiple hospitalizations§ History of severe aggression
1, 6
Progression
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Guidelines
APA 2004 PORT 2009 WFSBP 2012Canadian
Recommendations 2013
AFPBN 2013
First episode schizophrenia
Oral SGA Oral SGA or FGA (except
olanzapine or clozapine)
Oral SGA > Oral FGA LAI LAI SGA
Maintenance/ non-adherence LAI LAI LAI LAI LAI SGA or
FGA
Early Intervention
• Risk of relapse after first episode schizophrenia:§ AP discontinuation: 77% 1 year post d/c and >90% by year 2§ AP continuation: 3%
• Better treatment response• Increased social and occupational success• Decreased hospitalizations• Decreased cost burden on patient and healthcare system
4,12
KEY TAKEAWAY:
LAIAs may be used at any point and should be offered to any patient in which
maintenance AP therapy is required
Assessment Question #1
What is a potential benefit of starting LAIA therapy at the point of diagnosis?
A. Increased compliance, which has not proven to have a significant effect on the risk of relapse 1 year post-first episode.
B. Increased compliance, which has the potential to decrease the risk of relapse 1 year post-first episode from 77% to 3%.
C. Ease of rapid dose adjustments to control emerging symptoms.
D. Larger amount of AP options to choose from to treat the patient.
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DosingAP Initial Dose Maintenance Dose Injection Site
Aripiprazole ER 400 mg IM q month + 14 days PO dose
A 29 year old female with a history of schizophrenia presents to your clinic with symptoms of pseudoparkinsonism after several months of haloperidol decanoate therapy. She wishes to switch LAIAs but is fearful of the potential for weight gain associated with newer antipsychotics. Which LAIA is the most appropriate option?
A. Olanzapine pamoate (Zyprexa Relprevv ®)
B. Paliperidone palmitate (Invega Trinza ®)
C. Aripiprazole lauroxil (Aristada ®)
D. Risperidone ER (Perseris ®)
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Additional Considerations• Aripiprazole ER
• Requires 14 day oral overlap• Aripiprazole lauroxil
• Requires 21 day oral overlap OR administration with Aristada Initio ® IM X 1 + aripiprazole 30 mg PO X 1
• Fluphenazine decanoate• Requires at least 1 month of oral overlap
• Haloperidol decanoate• Pharmacokinetics highly variable; oral overlap based on symptoms
Additional Considerations• Olanzapine pamoate
• No oral overlap required• Patients stabilized on olanzapine 20 mg PO daily require q2 week
administration• REMS for post-injection delirium/sedation syndrome (PDSS)
• Paliperidone palmitate 1M• No oral overlap required• Must receive 2 loading dose injections during week 1• Can transition to Invega Trinza after stabilization for 4 months on Invega
• Requires 3 weeks oral overlap• Dosing frequency every 2 weeks• Must be refrigerated
• Risperidone ER• No oral overlap required• First subcutaneous option• Patients must be stabilized on risperidone 3 or 4 mg PO daily
Assessment Question #3
Which LAIA requires no oral overlap, making it an ideal choice for a patient who is very unreliable with taking oral medications?
A. Fluphenazine decanoate (Prolixin D ®)
B. Paliperidone palmitate (Invega Sustenna ®)
C. Aripiprazole ER (Abilify Maintena ®)
D. Haloperidol decanoate (Haldol Decanoate ®)
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Potential Advantages• Compliance• Easy identification of non-compliance• Clearer understanding of cause of relapse
• Reduced risk of intentional or accidental OD• Reduced concentration-dependent AEs
• Lower total daily dose compared to oral APs• Consistent contact with healthcare team• Decreased relapses/hospitalizations and better long-term outcomes
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Potential AdvantagesRisperidone LAI vs oral, 2015
LAI PO p-valuePsych relapse 5% 33% <0.001
Mean days to relapse 298.5 d 218.6 d <0.004
Psych hospitalization 5% 18.6% 0.05
D/c due to AEs 10% 21% 0.14
“Excellent level of adherence” on scale 1-5
95% 33% <0.001
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Potential Disadvantages
• Slow dose titration/ less flexibility for dosage adjustments
• Prolonged AEs after discontinuation
• Injection site pain
• Stigma
• Decreased AP options
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Potential Barriers
• Cost
• Transportation
• Limited access
• Convenience (e.g., hours of operation for injection administration sites)
• Prescriber/ patient perceptions
Overcoming Barriers• Cost
§ Coupons§ Assistance programs
§ Correct billing (e.g., completing prior authorizations, billing medical vs. prescription benefit)
§ Utilization of hospital free trial programs• Transportation
Depot APs have more advantages than oral formulations
3.51 3.51 2.72
Depot APs provide more security to the patient than do oral APs
2.89 3.51 2.47
With oral medication it is more likely to relapse
2.86 3.58 2.68
With depot medication patients are not reminded of their disorder each day
2.49 2.9 2.17
With oral medication, it is more likely that patients will forget to take their
tablets
2.42 3.3 2.16
1 (fully agree) to 5 (fully disagree)
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Attitudes Toward LAIAsI agree with… Pts w LAIA experience Pts w/out LAIA experience
I knew about the possibility to receive APs as a depot injection
90% 63%
My psychiatrists informed me about the option of depot AP trx
70% 21%
My psychiatrist recommended me to change to depot APs
60% 9%
I obtained information about depot APs from other sources
40% 22%
I feel sufficiently informed about different formulations of APs
76% 61%
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Overcoming Attitudes• Always educate and assess patient willingness to try an
LAIA
• Educate and discuss options with any patient requiring long term AP therapy
• Attempt multiple times
• Identify and mitigate misconceptions carried by psychiatrist, families, and patients
• Educate and promote LAIAs as an multidisciplinary team
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Expanding the Pharmacist's Role• Inpatient setting:
§ Identify patients eligible for LAIA use
§ Educate patients on the benefits of LAIAs
§ Assess patient willingness to try LAIAs
§ Collaborative practice agreements
• Dose LAIAs
• Modify oral counterpart
• Discharge prescriptions
Expanding the Pharmacist's Role
Expanding the Pharmacist's Role• Retail setting:§ Identify patients eligible for LAIA use§ Educate patients on the benefits of LAIAs§ Assess patient willingness to try LAIAs§ Pharmacist administration of LAIAs• Easy access• Convenient hours• Decreased stigma• Reminder alerts
Expanding the Pharmacist's Role• Ambulatory setting:
§ Identify patients eligible for LAIA use§ Educate patients on the benefits of LAIAs
§ Assess patient willingness to try LAIAs
§ Collaborative practice agreements
• Initiate and modify LAIAs and corresponding oral counterparts
• Initiate and modify medications used to treat AEs
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Assessment Question #4
In Missouri, pharmacists can work to overcome patient barriers to access of LAIA administration by administering LAIAs in retail pharmacies.
A. True
B. False
Ambulatory Model• Interdisciplinary team:
§ Psychiatrist: Assess patient for indication of LAI treatment (full scope of practice including oral medications for various psychiatric conditions if needed)
§ Pharmacist: Assess medication regimen, initiate LAI or authorize LAI refills, and titrate doses with collaborative practice agreement
§ Nurse: Complete nursing assessment and administers medication § Benefits specialist: Ensure coverage via prior authorizations with
insurance, patient assistance programs, etc. § Therapist: Group therapy and 1:1 counseling
Ambulatory Model
• Prescriptions filled via retail pharmacy
• Profit used to provide complementary:§ Transportation
§ Meals
§ Therapy
Results
• Patients have experienced a 68% decrease in hospital admissions
• 75% of patients experienced 0 hospitalizations
• 25 patients have attained jobs
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Summary• AP non-compliance is often not recognized, leading to
unnecessary dosage increases and medication changes
• LAIAs offer advantages to patients at the point of diagnosis and should not be reserved for the chronically ill
• Barriers to use and access of LAIAs exist but can be overcome
• Guidelines are beginning to incorporate use of LAIAs in first episode schizophrenia
• Choosing specific LAIAs should be based on patient specific factors and should involve shared decision making with patient
• Expanding the role of the pharmacist in the utilization of LAIAs can drastically improve access and patient outcomes
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Therapeutic Advances in Psychopharmacology. 2014;4(5):198-2192. CPNP. 2018-2019 Psychiatric Pharmacotherapy Review. [VitalSource]. Retrieved from https://online.vitalsource.com/#/books/9780985181888/3. Drug Facts and Comparisons. Facts & Comparisons [database online]. St. Louis, MO: Wolters Kluwer Health, Inc; March 2005. Accessed June, 2019.
4. Groves E and Hart J. Early Intervention Programs and Their Role in Recovery. National Alliance on Mental Health website. https://www.nami.org/About-NAMI/NAMI-News/2014/Early-Intervention-Programs-and-Their-Role-in-Reco. Updated June 2014. Accessed May, 2019.
5. Guzman F. Long-Acting Injectable Antipsychotics: A Practical Guide for Prescribers. Psychopharmacology Institute website. https://psychopharmacologyinstitute.com/antipsychotics/long-acting-injectable-antipsychotics-a-practical-guide-for-prescribers/. Updated February 2018. Accessed May 2019.
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7. Kreyenbuhl J, Buchanan R, Dickerson F, Dixon L. The Schizophrenia Patient Outcomes Research Team (PORT): Updated Treatment Recommendations 2009. Schizophr Bull. 2010 Jan; 36(1): 94–103. (PORT 2009)
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9. Llorca P, Abbar M, Courtet P, et al. Guidelines for the use and management of long-acting injectable antipsychotics in serious mental illness. BMC Psychiatry. 2013;13:340
10. Malla A, Tibbo P, Chue P, et al. Long-acting injectable antipsychotics: recommendations for clinicians. Can J Psychiatry. 2013;58:30S-35S11. Subotnik KL, Casaus LR, Ventura J, et al. Long-acting injectable risperidone for relapse prevention and control of breakthrough symptoms after a
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