Identifying patients and clinical scenarios for use of long-acting injectable antipsychotics – expert consensus survey part 1

Figures & data

Table 1 Demographics and practice characteristics of expert panel

Demographic and practice experience	Value
Mean (range) age, years	58 (42–82)
Male sex, n (%)	21 (62)
Mean (range) years in practice	25 (0–45)
Degree, n (%)
MD	24 (71)
PhD	6 (18)
DNP	2 (6)
PharmD	2 (6)
Involved in schizophrenia, bipolar disorder, or major depressive disorder research (within previous 5 years), n (%)	22 (65)
Mean (range) research experience, years	22 (0–52)
NIMH/NIH research grant as principal investigator, n (%)	15 (44)
Principal investigator for an industry-sponsored grant, n (%)	20 (59)
Practice environment	Value
Proportion of time spent seeing patients, n (%)
All/majority of the time	12 (36)
50% of the time	7 (21)
25% of the time	10 (29)
<10% of the time	5 (15)
Practice setting(s) where significant number of patients seen,a n (%)
Private practice	8 (25)
Public sector	11 (34)
Academic clinical or research setting	23 (69)
Mean percentage of time (range) spent treating or supervising the treatment of patients, by disease
Schizophrenia/schizoaffective disorder	30 (0–100)
Bipolar disorder	25 (0–75)
Major depressive disorder	24 (0–60)
Mean percentage of patients (range) with insurance coverage
Private insurance	30 (0–100)
Medicaid	33 (0–75)
Medicare	22 (0–70)
Uninsured	15 (0–70)
Mean percentage of patients (range) treated by age group
<18 years	10 (0–75)
18–34 years	35 (0–55)
35–65 years	41 (0–70)
>65 years	13 (0–65)
Mean percentage of patients (range) in practice currently receiving LAI, by disease
Schizophrenia/schizoaffective disorder	33 (0–100)
Bipolar disorder	11 (0–40)

Note:

a Some experts may have provided >1 response.

Abbreviations: LAI, long-acting injectable antipsychotic; NIMH/NIH, National Institute of Mental Health/National Institutes of Health.

Figure 1 Expert consensus on selecting appropriate patients with schizophrenia/schizoaffective and bipolar disorders for LAI treatment.

Notes: Rating scale: 1 = extremely inappropriate, 2–3 = usually inappropriate, 4–6 = sometimes appropriate, 7–8 = usually appropriate, 9 = extremely appropriate. Horizontal bars represent CIs. *Options that received highest ranking by ≥50% of respondents. Open bars indicate no consensus; shaded bars indicate consensus (dark shading = first line; medium shading = second line; light shading = third line). Colors of the survey questions correlate to the colors in the figure.
Abbreviation: LAI, long-acting injectable antipsychotic.

Table 2 Expert consensus on selecting patients with schizophrenia/schizoaffective disorder who are appropriate for LAI treatment based on treatment history

Rating	Patient with schizophrenia/schizoaffective disorder treated with antipsychotic medication for ≥2 years (mean [SD] ratinga)
	Assumed treatment adherence	Questionable treatment adherence
First line	Prefers LAI (8.8 [0.6])	Prefers LAI (8.8 [0.5])
	Has done well on LAI in the past (8.4 [0.9])	Has done well on LAI in the past (8.3 [1.3])
	Conflict in family related to adherence to oral medication (8.4 [0.9])	Conflict in family related to adherence to oral medication (8.3 [1.1])
	Frequently misses clinic appointments (8.1 [1.1])	Frequently misses clinic appointments (8.3 [1.0])
	Family/care partner does not support antipsychotic treatment regimen (7.5 [2.0])	Family/care partner does not support antipsychotic treatment regimen (7.6 [1.8])
	Patient with whom I have a good therapeutic alliance (7.1 [1.7])	Patient with whom I have a good therapeutic alliance (7.6 [1.5]) Has done well on oral antipsychotic medications in the past but has never been treated with an LAI (7.5 [1.3]) Concomitant maintenance treatment with other psychotropic medications (eg, mood-stabilizing agents, antidepressants) (7.5 [1.8]) Positive symptoms (hallucinations, delusions) have responded well to oral antipsychotic medications, but patient continues to have negative symptoms or cognitive symptoms/impairment (7.2 [1.6])
High second lineb	Concomitant maintenance treatment with other psychotropic medications (eg, mood-stabilizing agents, antidepressants) (6.6 [1.7])	Positive symptoms (hallucinations, delusions) have not responded to previous trials of oral antipsychotic medications (7.2 [2.2])
	Patient with whom I do not have a strong therapeutic alliance (6.6 [2.1])	Patient with whom I do not have a strong therapeutic alliance (7.1 [1.9])
	Positive symptoms (hallucinations, delusions) have responded well to oral antipsychotic medications, but patient continues to have negative symptoms or cognitive symptoms/impairment (6.5 [2.0])	Patient being treated with an antipsychotic indicated for treatment-resistant schizophrenia but is still experiencing positive symptoms (6.5 [2.4])
	Positive symptoms (hallucinations, delusions) have not responded to previous trials of oral antipsychotic medications (6.5 [2.3]) Has done well on oral antipsychotic medications in the past but has never been treated with an LAI (6.5 [2.0]) Patient being treated with an antipsychotic indicated for treatment-resistant schizophrenia but is still experiencing positive symptoms (6.2 [2.4]) History of refusing treatment with LAI (6.1 [2.1])	History of refusing treatment with LAI (6.5 [2.0])

Notes:

a Rating scale: 1 = extremely inappropriate, 2–3 = usually inappropriate, 4–6 = sometimes appropriate, 7–8 = usually appropriate, 9 = extremely appropriate; bold indicates an option rated 9 by ≥50% of the experts.

b High second-line options are those for which the upper value of the CI is ≥6.5, the boundary for first line.

Abbreviation: LAI, long-acting injectable antipsychotic.

Table 3 Expert consensus on selecting patients with bipolar disorder who are appropriate for LAI treatment based on treatment history

Rating	Patient with established diagnosis of bipolar disorder and treated with medication for ≥2 years (mean [SD] ratinga)
	Assumed treatment adherence	Questionable treatment adherence
First line	Prefers LAI (8.4 [0.9])	Prefers LAI (8.6 [0.7])
	History of suboptimal adherence to medications (7.6 [1.2])	Has done well on LAI in the past (8.3 [1.0])
	Has done well on LAI in the past (7.5 [1.5])	History of suboptimal adherence to medications (7.9 [1.3])
	Frequently misses clinic appointments (7.3 [1.7])	Frequently misses clinic appointments (7.4 [1.5]) Has failed to respond to lithium or anticonvulsant mood-stabilizing medications (7.1 [1.8]) Predominant history of manic relapse (7.1 [1.8]) Patient with whom I have a good therapeutic alliance (7.1 [1.8])
High second lineb	Has shown only partial response to lithium or anticonvulsant mood-stabilizing medications (6.9 [1.5])	Has shown only partial response to lithium or anticonvulsant mood-stabilizing medications (7.0 [1.7])
	Has failed to respond to lithium or anticonvulsant mood-stabilizing medications (6.8 [1.9])	Patient with whom I do not have a strong therapeutic alliance (6.9 [1.8])
	Patient with whom I have a good therapeutic alliance (6.8 [1.9])	Concomitant treatment with other mood-stabilizing agents or antidepressants (6.7 [2.0])
	Patient with whom I do not have a strong therapeutic alliance (6.6 [1.8]) Predominant history of manic relapse (6.5 [1.7]) Has done well on oral antipsychotic medications in the past but has never been treated with an LAI (6.0 [2.3])	Has done well on oral antipsychotic medications in the past but has never been treated with an LAI (6.6 [2.0])

Notes:

a Rating scale: 1 = extremely inappropriate, 2–3 = usually inappropriate, 4–6 = sometimes appropriate, 7–8 = usually appropriate, 9 = extremely appropriate; bold indicates an option rated 9 by ≥50% of the experts.

b High second-line options are those for which the upper value of the CI is ≥6.5, the boundary for first line.

Abbreviation: LAI, long-acting injectable antipsychotic.

Table 4 First- and high second-line expert ratings on the importance of potential facilitators for consideration of LAI use in a patient with schizophrenia/schizoaffective or bipolar disorder

Rating	Factors, beliefs, or perceptions about LAIs by healthcare providers that would facilitate consideration of an LAI (mean [SD] ratinga)
First line	Reduced risk of relapse and hospitalization (8.3 [1.0])
	Improved patient outcomes (8.2 [1.1])
	No need for patient to make a daily decision to take medication or remember to take medication daily (8.1 [0.9])
	Reduced symptoms because of continuous medication coverage (7.8 [1.6])
	Reduced burden and increased satisfaction for families (7.6 [1.3])
	Ability for the clinician to identify nonadherence immediately and intervene as soon as it is detected (7.6 [1.7])
	Better symptom control for patient who might abuse substances and reduce or stop medication (7.6 [1.4])
	Improved patient and physician satisfaction (7.4 [1.3])
	No or minimal concern about LAI being taken incorrectly or misused because staff are administering (reduced risk of unintentional or deliberate overdose) (7.2 [1.3])
High second lineb	Ability for the clinician to discriminate inadequate response due to lack of efficacy versus poor response due to adherence problems (7.1 [2.0])
	No need for patient to refill prescription for oral medication (6.9 [2.1])
	No concern about patient losing medication (6.9 [1.7])
	Ensures regular contact between patient and treatment team (6.7 [2.0])
	More time to focus on nonmedication-related issues rather than adherence issues in clinical sessions (6.7 [1.9])
	Reduced stigma associated with having to take daily psychiatric medication (6.7 [1.8])
	Patients who travel do not need to carry medication with them (6.4 [2.0])
	Less variation in peak-to-trough antipsychotic blood level with lower risk of peak-level side effects (6.3 [1.8])

Notes:

a Rating scale: 1 = not important at all, 2–3 = not very important, 4–6 = somewhat important, 7–8 = important, 9 = extremely important; bold indicates an option rated 9 by ≥50% of the experts.

b High second-line options are those for which the upper value of the CI is ≥6.5, the boundary for first line.

Abbreviation: LAI, long-acting injectable antipsychotic.

Figure S1 Organization of survey.

Note: To simulate the treatment decision process, questions were organized into 3 main areas: identifying patients, initiation of therapy, and maintenance treatment.

Abbreviation: LAI, long-acting injectable antipsychotic.

Table S1 Survey respondents

Anissa Abi-Dargham, MD, Stony Brook University

Rimal Bera, MD, University of California, Irvine

Kelly Bliss, DNP, Mental Bliss, PLLC

William Carpenter, MD, Maryland Psychiatric Research Center, University of Maryland School of Medicine

Leslie Citrome, MD, MPH, New York Medical College

Christoph Correll, MD, The Zucker Hillside Hospital and Hofstra Northwell School of Medicine

Colin Depp, PhD, University of California, San Diego

Nassir Ghaemi, MD, Tufts Medical Center

Radhika Gollapudy, MD

Philip Harvey, PhD, University of Miami

Rona Hu, MD, Stanford University

Rakesh Jain, MD, MPH, Private Practice, Austin, TX, USA

Anita Kablinger, MD, CPI, Carilion Clinic, Virgnia Tech Carilion School of Medicine

John Kane, MD, The Zucker Hillside Hospital

Samuel Keith, MD, University of New Mexico

Paul Maguire, MD, Community Partners of Strafford County

Stephen Marder, MD, University of California, Los Angeles

Michael Measom, MD, New Roads/AD Psychotherapy/Volunteers of America

David Miklowitz, PhD, University of California, Los Angeles, Semel Institute

Frederick Mittleman, MD, CODAC-Health Recovery Wellness

Ricky Mofsen, DO, Evolution Research Group

Mary Moller, DNP, MSN, Pacific Lutheran University

Diana Perkins, MD, University of North Carolina

Stacey Rawls, MD, Private Practice, Rocky Mount, NC

Martha Sajatovic, MD, Case Western Reserve University School of Medicine

Stephen Saklad, PharmD, BCPP, The University of Texas at Austin, College of Pharmacy, Pharmacotherapy Division

Nina R. Schooler, PhD, SUNY Downstate Medical Center

Aimee Schwartz, MD, Terros Health

Asim Shah, MD, Baylor College of Medicine

Tracey Skale, MD, Greater Cincinnati Behavioral

Roger Sommi, PharmD, BCPP, University of Missouri-Kansas City Schools of Pharmacy and Medicine

Georgia Stevens, PhD, Director, P.A.L. Associates: Partners in Aging & Long-Term Caregiving

Michael Thase, MD, University of Pennsylvania

Dawn Velligan, PhD, University of Texas Health Science Center at San Antonio

Table S2 General summary of expert opinion on the top barriers to the use of LAIs in the field

Barriers to the use of LAIs	Experts who listed barrier as ranking in the top 3 to limit the use of LAIs, n (N = 31)
Cost/not on formulary/not reimbursed by insurance	14
Negative perception/prescriber bias/stigma associated with injections as coercive, punitive, taking away patient autonomy/fear of impact on therapeutic alliance	14
Lack of knowledge/experience with LAIs and how to dose them	11
Lack of infrastructure and staff to use LAIs/time constraints/concern about it being more work to prescribe and provide LAIs	11
Perceptions about the types of patients for whom LAIs are appropriate (eg, only patients who are nonadherent, who have had multiple relapses, who are seen as the “worst of the worst,” with schizophrenia but not bipolar disorder)	9
Patient refusal/fear/dislike of injections	8
Concern about inability to adjust dosage/discontinue medication immediately as needed, concern about persistence of potential side effects	6
Problems presenting/explaining LAIs to patients	5
Availability of only a limited number of LAIs with FDA indications	3
Lack of family support	3
Believing patients will reject LAIs but not asking patients themselves	2
Concern about patients not returning for injections	2
Concern about pain at injection site	1
Overestimation of patients’ level of adherence	1
Patient having to come into the office biweekly or monthly for injections	1
Lack of awareness of the importance of adherence	1

Abbreviations: FDA, US Food and Drug Administration; LAI, long-acting injectable antipsychotic.