Summary

• Outcomes in patients with developmental disorders have not been reported in phase 3 clinical studies conducted with INVEGA SUSTENNA.
• The off-label use of INVEGA SUSTENNA has been reported in retrospective, observational studies^1-3 in pediatric and adolescent patients (≤20 years of age) with diagnoses including psychotic disorder, disruptive behavior disorder, attention-deficit or hyperactivity disorder (ADHD), intellectual disability (ID), and autistic disorder.

DOSAGE STRENGTH INFORMATION

Doses of paliperidone palmitate extended-release injectable suspension may be expressed in milligram equivalents of paliperidone (active moiety) or milligrams of paliperidone palmitate. Dosage information in this response has been converted to mg of paliperidone palmitate to reflect the commercially available dosage strengths in the United States. The conversion factor from mg eq. to mg is 1.56.

• INVEGA SUSTENNA doses expressed as 25, 50, 75, 100, and 150 mg eq. are equal to 39, 78, 117, 156, and 234 mg of paliperidone palmitate, respectively.

PUBLISHED LITERATURE

Retrospective Observational Studies

Sun et al (2024)¹ conducted a single-center retrospective chart review from October 2015 to October 2022 at an acute care psychiatric hospital in the United States (US). The dosing strategies, safety and effectiveness of 5 long-acting injectable (LAI) antipsychotics, including INVEGA SUSTENNA, in adolescent and pediatric patients with psychiatric disorders were evaluated.

Results

Patient demographics

• Forty-five patients were newly initiated on LAIs (mean age [±standard deviation (SD)], 15.6 [±1.67] years; male, 57.8%; Black or African-American, 60%; White, 37.8%), with a primary diagnosis of schizophrenia spectrum and other psychotic disorders (42.2%); bipolar disorders (31.1%); disruptive, impulse control, and conduct disorders (13.3%); autistic disorder (11.1%); and ADHD (2.2%).
• INVEGA SUSTENNA was the most commonly prescribed LAI antipsychotic (n=21; 46.7%).

Dosing regimens

• Of the patients receiving INVEGA SUSTENNA, 14 each received a loading dose and a maintenance dose per the adult dosing recommendation, and 7 each received a loading dose and a maintenance dose different from the adult dosing recommendation.
• The non-standardized dosing regimens for INVEGA SUSTENNA are summarized in Table: Non-Standard INVEGA SUSTENNA Dosing Regimens.

Length of stay and readmission rates

• For patients treated with INVEGA SUSTENNA, the mean (SD) length of hospital stay was 20.9 (13.0) days, with 5 patients (23.8%) being readmitted within 6 months, with a mean of 70.6 (32.6) days to readmission.

Adverse effects

• Five patients receiving INVEGA SUSTENNA reported adverse effects, including weight gain, metabolic effect, constipation, difficulty thinking or concentrating, and extrapyramidal symptoms (n=1, each).

Treatment retention

• Among the 26 of 45 patients who received psychiatric care post-hospitalization at an outpatient clinic, 10 (38.5%) adhered to LAI antipsychotics 6 months post-discharge.

Simpson et al (2024)² conducted a retrospective study between January 2016 and November 2019 in a community mental health clinic in the US to evaluate the safety and tolerability of the off-label use of INVEGA SUSTENNA in young and adolescent patients with autism spectrum disorder (ASD) and or ID.

Results

• Twenty-six patients were included (age range, 3 to 20 years; male, 76.9%; White, 53.8%; African American, 38.5%; Asian, 3.8%; and biracial, 3.8%).
• All patients had an ID diagnosis, and 92.3% had ASD. The most common psychiatric diagnoses were Intermittent Explosive disorder (88.5%), ADHD (38.5%), and anxiety (23.1%).
• At the time of INVEGA SUSTENNA initiation, all patients were on an antipsychotic and concomitant psychotropic medications, including alpha-2 agonists (44%), stimulants (36%), antidepressants (28%), and mood stabilizers (12%). Overall, at the time of INVEGA SUSTENNA initiation, the study population was using an average of 2.8 psychotropic medications.
• In 25 of 26 patients, noncompliance with oral antipsychotic medication was the leading reason to switch to INVEGA SUSTENNA.
• The most common starting maintenance dose (after standard initiation) of INVEGA SUSTENNA was 156 mg every month (n=11), ranging from 39 mg every month (n=1; male patient aged 3 years at initiation) to 156 mg every 3 weeks (n=4; male patients aged 10-15 years at initiation).
• Dosing tended to increase during the study period; the most common dosing of INVEGA SUSTENNA during the study period or at discontinuation was 234 mg every 3 weeks (n=10; aged 9-19 years during initiation).
• Patients were on INVEGA SUSTENNA for a mean (SD) period of 21.1 (14.0) months (n=25; range, 1-45 months); 17 patients continued with INVEGA SUSTENNA at the study endpoint.
  • Eight (32%) patients discontinued INVEGA SUSTENNA during the study period; the mean (SD) time before discontinuation was 17.5 (12.4) months.
  • The reasons for discontinuation were lack of efficacy, difficulty in attending visits to get injections, injections not well tolerated, oculogyric crisis, hyperprolactinemia, periods of shaking/sweating/ill symptoms for 36 to 48 hours after injections, planned taper off the medication, and ability to retake oral medication (n=1, each).
• There was a significant reduction in emergency department and hospital visits in the 12 months after INVEGA SUSTENNA initiation (P=0.02).
• No significant change in body mass index (BMI) was observed at initiation and the end of the study or discontinuation (BMI before initiation, 24.4; BMI after initiation, 25.5; P=0.15).

Fortea et al (2018)³ conducted a retrospective, observational study to assess the off-label use of LAI antipsychotics initiated in patients under the age of 18 during hospitalization in Barcelona between January 2013 and June 2016 (N=30).

Results

• Twenty-nine patients were switched from an oral antipsychotic and one patient was switched from intramuscular fluphenazine to risperidone.
  • Twelve patients initiated aripiprazole LAI (dose range: 300–400 mg), 11 risperidone LAI (dose range: 25–50 mg), and 7 INVEGA SUSTENNA (dose range: 78-234 mg), primarily due to low treatment compliance (90%) and poor insight (73.3%).
  • Patients initiated on INVEGA SUSTENNA (mean age: 16.5 years) had diagnoses including: psychotic disorder (86%), disruptive behavior disorder (43%), ADHD (29%), and ID (14%). In addition, 86% had comorbid cannabis misuse.
• Global functioning was assessed at baseline and discharge using the Children’s Global Assessment Scale (CGAS).
  • One risperidone and one paliperidone patient did not complete transition between oral and LAI at discharge. Oral prescription at discharge was not considered in the statistical analysis.
  • CGAS improved significantly (32 points; P<0.001) between admission and discharge, with no differences between LAIs (P=0.94). An exploratory analysis found no significant differences between patients with and without cannabis use.
• Two patients receiving INVEGA SUSTENNA reported adverse events [hyperprolactinemia (n=1) and akathisia (n=1)], which did not lead to treatment discontinuation.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 22 October 2024.