Initiating/maintaining long-acting injectable antipsychotics in schizophrenia/schizoaffective or bipolar disorder – expert consensus survey part 2

Figures & data

Figure 1 Procedures before initiating an LAI and partnering with patients.

Notes: (A) Appropriate treatment setting for initiating treatment with an LAI (rating scale: 1, not appropriate at all; 9, extremely appropriate), (B) important steps in initiating treatment with an LAI (rating scale: 1, not important at all; 9, extremely important), and (C) importance of discussing potential benefits of LAIs in motivating patients to use an LAI (rating scale: 1, not important at all; 9, extremely important). An asterisk in a bar represents an option that received the highest ranking of 9 by ≥50% of respondents. Horizontal bars represent CIs. Open bars indicate no consensus; shaded bars indicate consensus (dark shading: first line; medium shading: second line; light shading: third line). High second line: CI bar crosses the boundary with first line.
Abbreviation: LAI, long-acting injectable antipsychotic.

Table 1 Factors to consider in selecting an LAI

Patient-related factors	System-related factors	Medication-related factors
First-line ratings,a mean (SD)
Patient’s previous response to LAI,b 8.2 (1.1)	Out-of-pocket expense for the patient, 8.1 (1.0)	Clinician believes the chosen LAI will have the best tolerability, 7.8 (1.5)
Weight gain, metabolic syndrome, symptoms of hyperprolactinemia, tardive dyskinesia, or parkinsonism with previous antipsychotic, 7.9 (1.2)	Formulary or insurance restrictions, 8.0 (1.1)	Clinician believes the selected LAI has the best chance of being efficacious for the specific patient, 7.7 (1.5)
Symptoms of hyperprolactinemia with previous antipsychotic therapy, 7.7 (1.3)		Availability of longer-acting formulation (injections can be given less frequently), 7.7 (1.5)
Patient’s previous response to oral antipsychotic, 7.7 (1.3)		LAI that allows for longer interval when a dose is missed before oral augmentation required, 7.5 (1.0)
Tardive dyskinesia with previous antipsychotic therapy, 7.4 (1.9)		Availability of different formulations with varying dosing intervals, 7.1 (1.5)
Parkinsonism with previous antipsychotic therapy, 7.2 (1.4)		LAI that can be given via deltoid as well as gluteal injection, 7.0 (1.3)
High second-line ratings,a mean (SD)
Akathisia, sedation, or sexual dysfunction with previous antipsychotic, 7.1 (1.8)	Clinician’s personal experience using a specific LAI, 6.9 (2.2)	Availability of prefilled syringes for LAI administration, 6.8 (1.5)
Persistent positive symptoms in a patient with SCZ, 6.9 (1.9)	No availability of appropriately monitored refrigeration facilities, 6.6 (2.1)	Availability of multiple dosing strengths in prefilled syringes, 6.7 (1.6)
Sedation with previous antipsychotic therapy, 6.7 (1.8)		Properties of the specific antipsychotic molecule, 5.9 (2.0)
Sexual dysfunction with previous antipsychotic therapy, 6.5 (2.2)		Package insert recommends LAI dosing that takes into account hepatic metabolism status, 5.8 (1.7)
Persistent manic symptoms in a patient with bipolar disorder, 6.5 (1.8)
Medical comorbidity involving cardiovascular disease, 6.3 (1.9)
Medical comorbidity involving hepatic disease/dysfunction, 6.2 (2.0)
Borderline or prolonged QTc interval, 6.2 (2.1)
Persistent depressive symptoms in a patient with SCZ, 6.0 (1.9)
Persistent depressive symptoms in a patient with bipolar disorder, 5.9 (2.1)
Persistent negative symptoms in a patient with SCZ, 5.8 (2.2)

Notes:

a CIs of mean ratings were used to designate first-line or high second-line ratings (ie, items were first line if the bottom of the CI boundary was >6.5 and high second line if the bottom of the CI boundary was ≥3.5 and the top of the CI boundary was >6.5).

b Options that received the highest rating of 9 by ≥50% of experts.

Abbreviations: LAI, long-acting injectable antipsychotic; SCZ, schizophrenia/schizoaffective disorder.

Figure 2 Optimizing maintenance treatment and supporting LAI adherence.

Notes: (A) Optimal interval between injections (rating scale: 1, extremely inappropriate; 9, extremely appropriate) and (B) effectiveness of strategies during maintenance treatment with an LAI to optimize the patient’s adherence to appointments for LAI administration (rating scale: 1, likely to be ineffective; 9, likely to be effective). Horizontal bars represent CIs. Open bars indicate no consensus; shaded bars indicate consensus (dark shading: first line; medium shading: second line; light shading: third line). High second line: CI bar crosses the boundary with first line.
Abbreviation: LAI, long-acting injectable antipsychotic.

Table 2 Strategies for an inadequate response to an LAI in patients with schizophrenia/schizoaffective or bipolar disorder

Type of persistent or breakthrough symptom	First linea	High second linea
Schizophrenia/schizoaffective disorder
Positive symptoms (eg, hallucinations, delusions, aggression)	• Switch to a medication approved for treatment-resistant schizophrenia, 7.4 (1.9)	• Switch to an alternative LAI with a different molecular base, 6.5 (1.9) • Add the same oral antipsychotic as the LAI, 6.3 (2.0) • Decrease time period between injections to a shorter interval,b 6.1 (2.4)
Negative symptoms	• Switch to a medication approved for treatment-resistant schizophrenia, 6.5 (2.4)
Cognitive symptomsc
Bipolar disorder
Manic symptoms	• Switch to a different mood stabilizer if the patient is currently being treated with one, 7.4 (1.6) • Add lithium, 7.4 (1.3) • Add an anticonvulsant mood stabilizer the patient has not previously received, 7.4 (1.3)	• Add an anticonvulsant mood stabilizer to which the patient has previously had at least a partial response, 7.1 (1.8)
Depressive symptoms		• Add lithium, 6.3 (1.9) • Add an antidepressant medication if the patient is already receiving lithium or an anticonvulsant mood stabilizer, 6.1 (2.3) • Add an anticonvulsant mood stabilizer, 6.0 (2.0)
Psychotic symptoms		• Switch to a medication approved for treatment-resistant schizophrenia, 5.9 (2.6) • Switch to an alternative LAI with a different molecular base, 5.8 (2.1) • Add the same oral antipsychotic as the LAI,b 5.7 (2.4)

Notes:

a CIs of mean ratings were used to designate first-line or high second-line ratings (ie, items were first line if the bottom of the CI boundary was >6.5 and high second-line if the bottom of the CI boundary was ≥3.5 and the top of the CI boundary was >6.5).

b No consensus was reached.

c No first-line or high second-line recommendations; no consensus on any second-line strategy.

Abbreviation: LAI, long-acting injectable antipsychotic.

Table 3 Summary of first-line recommendations for initiating and maintaining treatment with an LAI

Practices/procedures	Recommendations
Agreeing to LAI trial	• Discuss risks/benefits with patient and family/care partners • Obtain patient agreement • Document discussion with patient • Provide educational materials
Choosing an agent	Consider: • Patient’s previous response to specific antipsychotics, including history of side effects with different agents • Metabolic and EPS side effects experienced with previous antipsychotics • Out-of-pocket expense and formulary restrictions • Clinician’s expectation of good tolerability and efficacy for specific LAI • Availability of formulations with varying dosing intervals • Option for deltoid or gluteal injection
LAI initiation	• Sufficient tolerability to the LAI should be established for the oral medication before initiating LAI with that same molecule • When starting LAI, use concomitant oral antipsychotic according to package insert • Start with intended maintenance dose for most patients • Give second injection according to schedule in package insert, unless symptoms increase before the end of dosing interval
LAI trial	• Duration of trial should allow achievement of steady state or one to two cycles after steady state is reached • Measure treatment response based on the presence of positive symptoms and/or functional status (SCZ) or based on psychotic symptoms, manic/hypomanic symptoms, functional status, and/or mixed symptoms (BP) • If steady state of maximum tolerated dose is reached but symptoms persist:  ◦ (SCZ) positive symptoms – switch to medication approved for treatment-resistant schizophrenia; negative or cognitive symptoms – no first-line consensus  ◦ (BP) manic symptoms – add lithium or mood stabilizer or switch to a different mood stabilizer; depressive or psychotic symptoms – no first-line consensus
Maintenance treatment	• Support continued injections through  ◦ Appointment reminders (by clinic [phone], family member, care partner, peer specialist, counselor)  ◦ LAI administration in the home by a mental health professional • Address side effects • Monitor body weight, BMI, blood pressure, liver function, metabolic parameters, prolactin, EPS

Abbreviations: BMI, body mass index; BP, bipolar disorder; EPS, extrapyramidal symptoms; LAI, long-acting injectable antipsychotic; SCZ, schizophrenia/schizoaffective disorder.

Table S1 Frequency of medical monitoring during and after the first 6 months of treatment with LAIs

During the first 6 months of LAI treatment
Experts’ endorsing option, n	Do not monitor	Baseline	After 1 month	After 2 months	After 3 months	After 6 months
Body weight/BMI	0	30	28	24	24	29
Blood pressure	2	29	20	13	20	23
Electrocardiogram	16	17	6	1	1	8
Fasting glucose level	0	28	9	4	16	23
Fasting lipid levels	0	28	7	3	12	23
HbA1c	2	27	3	0	11	23
Liver function testing	5	24	5	1	12	15
Prolactin level if the patient is being treated with a medication with the potential to raise prolactin	10	15	4	2	10	16
Standardized assessments for extrapyramidal symptoms (parkinsonism, akathisia)	5	22	17	11	22	22
Standardized assessments for tardive dyskinesia	5	25	7	6	17	25
Waist circumference	15	16	7	8	14	16
After the first 6 months of LAI treatment
Experts’ endorsing option, n	Do not monitor	At 8 months	At 10 months	At 1 year	Every 6 months thereafter	Every year thereafter
Body weight/BMI	0	16	15	21	25	11
Blood pressure	1	11	10	22	17	16
Electrocardiogram	14	0	0	11	3	14
Fasting glucose level	1	1	1	22	12	18
Fasting lipid levels	0	1	0	21	10	20
HbA1c	2	1	0	20	10	18
Liver function testing	4	0	0	18	7	19
Prolactin level if the patient is being treated with a medication with the potential to raise prolactin	12	1	1	12	6	14
Standardized assessments for extrapyramidal symptoms (parkinsonism, akathisia)	5	9	8	18	21	6
Standardized assessments for tardive dyskinesia	5	4	4	16	21	8
Waist circumference	14	3	3	13	11	7

Abbreviations: BMI, body mass index; LAI, long-acting injectable antipsychotic.