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Long-Acting Injectable Antipsychotics: The Benefits and Barriers
Danielle Moses, PharmD, BCPPPsychiatric Clinical PharmacistSSM Health DePaul Hospital
Adjunct 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.
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
8
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.
DosingAP Initial Dose Maintenance Dose Injection Site
Aripiprazole ER 400 mg IM q month + 14 days PO dose
400 mg IM q month;May be adjusted from 160 –
300 mg for tolerability or CYP interactions
Deltoid or gluteal
Aripiprazole lauroxil 10 mg = 441 mg q month15 mg = 662 mg q month, 882 mg q 6
weeks, or 1064 mg q 2 months>20 mg = 882 q month
+21 days PO dose
OR+
Aristada Initio® 675 mg IM X 1 + aripiprazole 30 mg PO X 1
441-882 mg IM q monthOR 882 mg IM q 6 weeksOR 1064 mg q 2 months
441 mg, Aristada Initio® 675 mg = deltoid or gluteal
662-1064 mg = gluteal
DosingAP Initial Dose Maintenance Dose Injection Site
Fluphenazine decanoate 6.25-25 mg IM q 2 weeksOR
10 mg = 12.5 mg IM q 3 weeks+ 50% PO dose until 2nd injection,
then consider d/c
10 mg = 12.5 mg IM q 3 weeks
Max = 100 mg IM
Gluteal*Deltoid has been successfully
studied
Haloperidol decanoate 10-20 x PO dose
Initial dose must not exceed 100 mg IM; if dose conversion requires > 100
mg, divide dose in 2 injections separated by 3-7 days
+PO haloperidol; taper and d/c
following 2-3 injections
10-15 X PO dose IM q 4 weeks
Gluteal*Deltoid has been successfully
studied
DosingAP Initial Dose Maintenance Dose Injection Site
Olanzapine pamoate 10 mg = 210 mg IM q2 weeks X 4 doses or 405 mg q4 weeks X 2 doses
15 mg = 300 mg IM q2 weeks X 4 doses
20 mg = 300 mg IM q2 weeks
10 mg = 150 mg IM q2 weeks or 300 mg q4 weeks
15 mg = 210 mg IM q2 weeks or 405 mg q4 weeks
20 mg = 300 mg IM q2 weeks
Gluteal
Paliperidone palmitate 1M
234 mg IM day 1 then 156 mg IM day 8 (+/- 4 days)
CrCl 50-79 mL/min:156 mg IM day 1 then 117 mg IM day
8 (+/- 4 days)
3 mg = 39-78 mg IM q4 weeks6 mg = 117 mg IM q4 weeks9 mg = 156 mg IM q4 weeks12 mg = 234 mg IM q4 weeks
Deltoid or gluteal
DosingAP Initial Dose Maintenance Dose Injection Site
Paliperidone palmitate 3M
78 mg = 273 mg IM117 mg = 410 mg IM156 mg = 546 mg IM234 mg = 819 mg IM
273-819 mg IM q 3 months Deltoid or gluteal
Risperidone microspheres
25 mg IM q2 weeks + 21 days PO dose
25-50 mg IM q2 weeks Deltoid or gluteal
Risperidone ER 3 mg = 90 mg SQ4 mg = 120 mg SQ
90-120 mg SQ q4 weeks Abdomen
Adverse Effect ProfilesFirst Generation Antipsychotics
Sedation Anticholinergic EPS Hypotension QTc
fluphenazine Low Low Very High Low Low
haloperidol Very Low Very Low Very High Very Low High
Adverse Effect ProfilesSecond Generation Antipsychotics
Sedation EPS Hypotension QTc Metabolic
aripiprazole Low Low Low Very Low Very Low
olanzapine Moderate Low Low Low High
paliperidone Low Mod-High Moderate Low-Mod Moderate
risperidone Low Moderate Moderate Low-Mod Moderate
Assessment Question #2
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 ®)
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
Sustenna• Paliperidone palmitate 3M
• Dosing frequency every 3 months
Additional Considerations• Risperidone microspheres
• 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 ®)
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
5, 6, 10, 12
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
11
Potential Disadvantages
• Slow dose titration/ less flexibility for dosage adjustments• Prolonged AEs after discontinuation• Injection site pain
• Stigma• Decreased AP options
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§ Expand locations (e.g., retail pharmacies)§ Incorporate complementary
transportation into business model
Overcoming Barriers
• Limited access/ convenience
§ Expand locations
§ Incorporate LAIA administration into more professions
• Prescriber/ patient perceptions
§ Education
• Expanding the pharmacist’s role
Attitudes Toward LAIAs
• Patients have more negative perceptions than psychiatrists and relatives
• Prominent patient fears: coercion and pain
• 67% of patients did not receive information about LAIAs from their psychiatrist
• <10% of psychiatrists offer LAIAs after first psychotic episode
6
Attitudes Toward LAIAsPsychiatrists Patients Relatives
Depot APs have more advantages than disadvantages
2.99 3.23 2.69
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)
6
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%
6
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
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
Assessment Question #4
In Missouri, pharmacists can work to overcome patient barriers to access of LAIA administration by administering LAIAs in retail pharmacies.
A. TrueB. 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
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
Resources1. Brissos S, Veguilla M, Taylor D, Balanza-Martinez V. The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal.
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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