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INVEGA SUSTENNA®

(paliperidone palmitate)

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INVEGA SUSTENNA® (paliperidone palmitate)
Medical Information

Adverse Event - Movement Disorders

Last Updated: 08/19/2026

SummarY

  • In a pooled analyses of double-blind, placebo-controlled, acute treatment trials in patients with schizophrenia, extrapyramidal symptoms (EPS) were among the most common drug-associated adverse events (AEs; at least 5% in patients treated with INVEGA SUSTENNA and more than twice the placebo rate).1 No occurrences of these AEs reached this threshold in the long-term double-blind, placebo-controlled study in subjects with schizoaffective disorder.2
  • Tardive dyskinesia (TD) is a syndrome of potentially irreversible, involuntary, dyskinetic movements. Occurrence of TD is associated with treatment with several medication classes, including antipsychotic drugs.3 If signs and symptoms of TD appear in a patient treated with INVEGA SUSTENNA, drug discontinuation should be considered.

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 INVEGA SUSTENNA and INVEGA TRINZA dosage strengths. 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.
  • INVEGA TRINZA doses expressed 546 and 819 mg of paliperidone palmitate are equal to 350 and 525 mg eq., respectively.

CLINICAL STUDIES


Clinical Trial Data
Trial Design
EPS Resultsa
SCHIZOPHRENIA
Double-Blind Clinical Trials
Fleischhacker et al (2011)4 conducted a 53-week, randomized, DB, active-controlled, parallel-group, multicenter, comparative study assessing the efficacy and safety of INVEGA SUSTENNA compared to RLAI in the treatment of patients with an acute exacerbation of schizophrenia (n=747, safety analysis set).
INVEGA SUSTENNA + Oral PBO: Flexibly dosed INVEGA SUSTENNA (39, 78, 117, or 156 mg) via gluteal injection + oral PBO supplementation every 4 weeks following an initiation dose of INVEGA SUSTENNA 78 mg administered on days 1 and 8.
RLAI + Oral RIS: Flexibly dosed oral RIS (1-6 mg/day) was administered for 4 weeks initially and for 3 weeks following each RLAI dosage increase. Patients received a PBO injection on day 1, RLAI 25 mg on days 8 and 22 and flexibly dosed RLAI (25, 37.5, or 50 mg) administered every 2 weeks thereafter via gluteal injection.
  • The incidence of EPS-related AEs was low and similar for both treatment groups except hyperkinesias, which were lower for the INVEGA SUSTENNA + PBO group compared to the RLAI + RIS group (6% vs 10%, respectively).
  • Serious TEAEs:
    • Akathisia occurred in 2 patients in the INVEGA SUSTENNA group and did not result in study discontinuation.
    • Neuroleptic malignant syndrome (NMS) was reported in 1 patient on INVEGA SUSTENNA and resulted in study discontinuation.
  • No occurrence of TD was reported.
Pandina (2011)5 conducted a 13-week, randomized, DB, double-dummy, active-controlled, parallel-group, multicenter study assessing non-inferiority of INVEGA SUSTENNA to RLAI in the treatment of patients with schizophrenia (n=1214, safety analysis set).
INVEGA SUSTENNA (n=606): Deltoid injection of INVEGA SUSTENNA 234 mg on day 1 followed by a 156-mg deltoid injection on day 8; thereafter, patients received flexibly dosed INVEGA SUSTENNA injections on days 36 (78 or 156 mg) and 64 (78, 156, or 234 mg) in either the deltoid or gluteal muscle.
RLAI (n=608): RLAI 25 mg on days 8 and 22, followed by 25 or 37.5 mg on days 36 and 50; thereafter, patients received flexible doses of 25, 37.5, or 50 mg on days 64 and 78, all in the gluteal muscle. Oral supplementation with RIS (1-6 mg) was administered for the first 28 days.
  • Optional supplementation with RIS was permitted under certain circumstances outlined in the protocol.
  • The most common EPS-related TEAEs were akathisia (<5% in both groups) and tremor (<3% in both groups).
  • TD was reported in 1 patient in each group and was neither serious nor severe. In the INVEGA SUSTENNA-treated patient, the event resolved 19 days after onset on day 11, and the patient received 2 additional injections without worsening on the AIMS total score. In the RLAI-treated patient, the patient had received fluphenazine decanoate prior to study entry and AIMS score improved during continued use of RLAI.
  • No clinically relevant changes in EPS rating scales (SAS, BARS, AIMS) were reported.
  • Anti-EPS medication was used by 28% of INVEGA SUSTENNA-treated patients and 24% of RLAI-treated patients at baseline, and by 7% of INVEGA SUSTENNA-treated patients and 5% of RLAI-treated patients at the last week of the DB period.
Hough (2010)6 conducted a longer-term, DB, randomized, multicenter, PBO-controlled, parallel group study examining the efficacy and safety of INVEGA SUSTENNA in delaying time-to-relapse in schizophrenic patients following an initial 9-week, OL transition phase and 24-week, OL maintenance phase (n=849, transition and maintenance population; n=408, DB safety analysis set).
Dosing Schedule (All doses administered IM via gluteal muscle):
9-week OL transition phase: INVEGA SUSTENNA 78 mg on day 1 and day 8 followed by adjustable INVEGA SUSTENNA doses (39, 78, or 156 mg) administered every 4 weeks for the rest of the transition period.
24-week OL maintenance phase: Adjustable INVEGA SUSTENNA doses (39, 78, or 156 mg) administered every 4 weeks for the first 12 weeks followed by fixed INVEGA SUSTENNA doses of 39, 78, or 156 mg every 4 weeks for the last 12 weeks.
DB phase: Fixed INVEGA SUSTENNA doses of 39, 78, or 156 mg (n=205) or PBO (n=203) every 4 weeks.
52-week OLE study: All patients (n=388) received gluteal injections of INVEGA SUSTENNA beginning with a 78 mg dose followed by flexible dosing (39, 78, 117, or 156 mg) once every 4 weeks for 12 injections.7
  • One case of TD was reported as mild and nonserious during the transition period.6
  • During the transition and maintenance periods, EPS-related AEs occurred in 9% of patients; during the DB period, EPS-related AEs occurred in 2% of patients who received PBO and 6% of patients who received INVEGA SUSTENNA.
  • The incidence of EPS-related TEAEs during the OLE phase was low (6% of patients); tremor was the most frequently reported EPS-related TEAE (2%). None of the EPS-related TEAEs were serious or resulted in treatment discontinuation.7
  • One patient in the PBO/INVEGA SUSTENNA group developed mild TD.
  • From OLE baseline to endpoint, no clinically meaningful changes in median scores on the global AIMS, BARS, and SAS scales were observed.
  • According to BARS results at OLE endpoint, akathisia was absent in 95% of patients.
  • Anti EPS medication was used by 8.5% of patients.
Gopal et al (2010)8 conducted a 13-week, multicenter, randomized, DB, PBO-controlled, dose-response study evaluating the efficacy and safety of 3 fixed doses of INVEGA SUSTENNA (78, 156, or 234 mg), administered via gluteal injection on days 1, 8, 36 and 64, in patients with schizophrenia (n=388, safety analysis set).
  • Incidence of EPS-related adverse events was reported as low (≤5% of patients in INVEGA SUSTENNA and PBO groups).
  • One case of akathisia was associated with INVEGA SUSTENNA 234 mg and reported as serious.
Kramer et al (2010)9 conducted a 9-week, DB, randomized, international study comparing the safety and efficacy between INVEGA SUSTENNA (2 fixed doses) and PBO in the treatment of adults with schizophrenia (n=247). Patients were randomized to receive gluteal IM injections of INVEGA SUSTENNA 78 mg (n=79), INVEGA SUSTENNA 156 mg (n=84), or PBO (n=84), without oral supplementation, on days 1, 8, and 36.
  • EPS-related TEAEs occurred in 6% (n=5/84) of INVEGA SUSTENNA 156 mg patients and in 0% of INVEGA SUSTENNA 78 mg (n=0/79) and PBO (n=0/84) patients.
  • No EPS event was rated as severe in intensity or resulted in the discontinuation of treatment.
  • Parkinsonism, the most commonly reported EPS-related AE, occurred more frequently in the INVEGA SUSTENNA groups (156 mg: 8%; 78 mg: 5%) compared to PBO (1%).
  • No clinically relevant between group differences were observed in AIMS, BARS, or SAS scores.
  • Anti-EPS medication was used by 21% of patients who received INVEGA SUSTENNA 156 mg, 10% of those who received INVEGA SUSTENNA 78 mg, and 7% of those who received PBO.
Nasrallah et al (2010)10 conducted a 13-week, phase 3, multicenter, randomized, DB, PBO-controlled, parallel group, international dose-response study evaluating the efficacy and safety of 3 fixed doses of INVEGA SUSTENNA (39, 78, or 156 mg), administered by gluteal IM injection on days 1, 8, 36, and 64, in patients with schizophrenia (n=517, safety analysis set).
  • No clinically relevant between group differences were observed with regard to AIMS, BARS, and SAS scores.
  • Parkinsonism, the most commonly reported EPS-related AE, was observed at a similar rate for the total INVEGA SUSTENNA and PBO groups (6% vs 5%, respectively). No discontinuations due to EPS-related AEs were reported.
  • Anti-EPS medication was used by 4-7% of patients who received INVEGA SUSTENNA and by 6% of those who received PBO at endpoint.
Pandina et al (2010)11 13-week, phase 3, randomized, DB, PBO-controlled, international dose response INVEGA SUSTENNA study conducted in patients experiencing an acute exacerbation of established schizophrenia (n=652).
Initiation Dose: Day 1 (Deltoid IM Inj)
  • INVEGA SUSTENNA 234 mg (n=488)
  • PBO (n=164)

Fixed Dose: Day 8, 36, and 64 (Deltoid or Gluteal IM Inj)
  • INVEGA SUSTENNA 234 mg (n=163)
  • INVEGA SUSTENNA 156 mg (n=165)
  • INVEGA SUSTENNA 39 mg (n=160)
  • PBO (n=164)
  • The most frequently reported EPS across all treatment groups was akathisia: <6% of patients (INVEGA SUSTENNA 234 mg: 5.5%; INVEGA SUSTENNA 156 mg: 4.8%; INVEGA SUSTENNA 39 mg: 1.3% vs PBO: 4.9%).
  • The overall proportion of EPS-related TEAEs in the INVEGA SUSTENNA groups was 9%, and none were serious or resulted in treatment discontinuation.
  • Anti-EPS medication was used by 8-12% of patients who received INVEGA SUSTENNA and by 9% of those who received PBO at endpoint.
  • No instances of TD were reported.
Hough (2009)12 conducted a 25-week, randomized, DB, multicenter, cross-over study assessing the safety and tolerability of INVEGA SUSTENNA administered via a deltoid or gluteal IM injection in adults with stable schizophrenia (n=252, safety analysis set).
Patients were randomized to receive one of two injection-site sequences (Period 1: Doses administered on days 1, 8, 36, and 64 followed by Period 2: Doses administered on days 92, 120, and 148).
1) GD (Gluteal IM inj during period 1 followed by Deltoid IM inj during period 2)
2) DG (Deltoid IM inj during period 1 followed by Gluteal IM inj during period 2)
INVEGA SUSTENNA doses:
78 mg: GD (n=40); DG (n=42)
117 mg: GD (n=44); DG (n=40)
156 mg: GD (n=40); DG (n=46)
  • The incidence of EPS-related TEAEs was low for all INVEGA SUSTENNA patients (according to the study investigators), did not significantly differ between injection sites, and did not increase with increasing dosages.
  • Incidence of EPS-related TEAEs per injection site:
    • Period 1: Deltoid: 7% (n=9/126); Gluteal: 10% (n=12/123)
    • Period 2: Deltoid: 2% (n=2/91); Gluteal: 6% (n=6/101)
  • Akathisia (3%), muscle spasm (2%), and tremor (2%) were the most commonly reported EPS-related adverse events.
  • Changes in EPS rating scales were not clinically significant.
  • 10% of patients used anticholinergic medications.
Post Hoc Analyses
Gopal et al (2013)13 conducted a post hoc analysis of pooled data from randomized, DB, PBO-controlled studies in patients with acute exacerbation of schizophrenia, to determine the incidence and time-course of EPS-related AEs (n=2256 non PBO-treated patients).
  • In three 6-week studies, patients received maintenance doses of 3-15 mg oral PALI ER or PBO daily. In four 9- to 13- week studies, patients received maintenance doses of 39–234 mg INVEGA SUSTENNA or PBO monthly, after initiation dosing.
  • On EPS rating scale total scores, least squares mean differences for PALI ER minus INVEGA SUSTENNA at endpoint were: AIMS, -0.04 (NS); BARS, 0.09 (P=0.023); SAS, 0.04 (P<0.0001).
  • Overall incidence of EPS-related AEs was 10.7% (138/1293) for INVEGA SUSTENNA, 19.8% (191/963) for PALI ER, 9% (46/510) for LAI-PBO, and 11% (39/355) for oral-PBO.
  • Anticholinergic medication was used by 12% of the INVEGA SUSTENNA group and 17% of the PALI ER group.
Gopal et al (2013)3 conducted a post hoc analysis of pooled data from completed long-term (≥6 months) studies aimed at estimating and comparing the incidence of TD
  • 4 schizophrenia studies with INVEGA SUSTENNA (n=1689)
  • 5 schizophrenia studies (n=2054) and 1 bipolar study with PALI ER (n=614)

Evaluations:
  • Spontaneously reported AEs
  • Schooler-Kane criteria: utilizing AIMS total scores (items 1-7), patients scoring ≥2 on 2 or more items or ≥3 on at least 1 item were identified with probable (≥3 months duration) or persistent (≥6 months total) TD
  • Incidence of TD was low and comparable between treatment groups with no overlap between cases reported as an AE vs those identified via Schooler-Kane criteria. No cases of TD were identified during the bipolar study.
  • Incidence of dyskinesias (total AIMS score ≥3) was highest within the first month of treatment for both INVEGA SUSTENNA (13.1%) and PALI ER (11.7%) and steadily decreased over time.
  • Persistent TD was identified in 3 patients (INVEGA SUSTENNA [0.12%]: [#1: mean age: 43 years; mean dose: 78 mg; exposure: 621 days; #2: mean age: 57 years; mean dose: 80.79 mg; exposure: 372 days]; PALI ER [0.05%]: mean age: 53 years; mean dose: 9.18 mg; exposure: 417 days). Two patients completed the study and 1 withdrew due to problems with visit scheduling.
  • Probable TD (Schooler-Kane criteria) was identified in 4 PALI ER (0.19%) and 2 INVEGA SUSTENNA (0.12%) patients.
  • There were no discontinuations due to TD reported as an AE.
Additional Double-Blind Clinical Trials
Savitz et al (2016)14 conducted a randomized, DB, parallel-group, multicenter, noninferiority study of INVEGA TRINZA and INVEGA SUSTENNA.
  • During the OL stabilization phase, 1429 patients received INVEGA SUSTENNA in the following doses: Initiation doses, IM deltoid (234 mg on day 1; 156 mg on day 8); Weeks 5 and 9: flexible dosing between 78-234 mg (deltoid or gluteal administration). The week 13 dose was the same as week 9.
  • Based on pre-defined criteria, patients who were clinically stable after completing the OL phase were randomized (1:1) into the 48-week, DB phase. Patients received fixed doses of INVEGA SUSTENNA every 4 weeks (78, 117, 156 or 234 mg; n=512) or INVEGA TRINZA every 3 months (273, 410, 546, 819 mg; n=504) in the deltoid or gluteal muscle.
  • The mean duration of exposure was 295.1 days for INVEGA TRINZA at a mean dose of 647.01 mg and 286.7 days for INVEGA SUSTENNA at a mean dose of 185.8 mg.
  • During the OL phase, 13% of patients experienced EPS-related TEAEs. The incidence of EPS-related TEAEs was similar between the INVEGA TRINZA and INVEGA SUSTENNA groups during the double-blind phase (8% and 7%, respectively).
  • Akathisia was the most common TEAE reported in 6% of the patients in the OL phase, and 4% and 3% of patients in the INVEGA TRINZA and INVEGA SUSTENNA group, respectively, during the double-blind phase.
  • TD was reported in 3 patients (INVEGA SUSTENNA [OL phase]; INVEGA SUSTENNA [OL/DB phases]; INVEGA TRINZA [DB phase].
  • More patients in the INVEGA TRINZA vs INVEGA SUSTENNA group received anti-EPS treatment during the DB phase (16% vs 13%, respectively).
McEvoy et al (2014)15 conducted the ACLAIMS trial, a DB, randomized, multisite, parallel-group US clinical trial comparing the effectiveness of INVEGA SUSTENNA versus HAL decanoate for the maintenance treatment of schizophrenia or schizoaffective disorder.
Long-acting injectable treatment (≤24 months):
  • INVEGA SUSTENNA (n=147): Initiation doses, IM deltoid (234 mg on day 1; 156 mg on day 8); Maintenance doses, IM deltoid or gluteal (117 mg monthly)
  • HAL decanoate (n=147): Initiation doses, IM deltoid (50 mg on day 1; 50 mg on day 8); Maintenance doses, IM deltoid or gluteal (75 mg on days 28 and 56, then 50 mg monthly)
  • Mean monthly doses of INVEGA SUSTENNA and HAL decanoate ranged from 129-169 mg and 67-83 mg, respectively. Patients were followed for a median of 488 days.
  • No statistically significant differences between INVEGA SUSTENNA and HAL decanoate were observed in baseline change scores for AIMS global (0.43 vs 0.50, respectively; P=0.39) and SAS (0.21 vs 0.25, respectively; P=0.34) measures.
  • The incidence of probable TD was not significantly different between treatment groups (INVEGA SUSTENNA: 10.6% vs HAL decanoate: 15.4%; P=0.24).
  • Increases in the BARS global score were significantly greater for HAL decanoate vs INVEGA SUSTENNA patients (0.73 vs 0.45, respectively; P=0.006).
  • Fewer INVEGA SUSTENNA vs HAL decanoate patients started medications to treat parkinsonism (15.8% vs 29.3%, respectively; P=0.007) and akathisia (3.6% vs 11.0%, respectively; P=0.03).
  • The following percentages of patients discontinued treatment due to neurologic AEs (clinical judgment):
    • Akathisia: INVEGA SUSTENNA: 0.7% (n=1); HAL decanoate: 1.4% (n=2)
    • Parkinsonism: INVEGA SUSTENNA: 0.7% (n=1); HAL decanoate: 2.0% (n=3)
    • TD: INVEGA SUSTENNA: 0.7% (n=1); HAL decanoate: 2.7% (n=4)
Takahashi et al (2013)16 conducted a 13-week, randomized, DB, PBO-controlled trial assessing the safety and efficacy of INVEGA SUSTENNA in Asian patients with schizophrenia (N=323; mean age: 45 years; 57% male).
  • INVEGA SUSTENNA, n=159: 234 mg on day 1 (deltoid IM); 156 mg on day 8 (deltoid IM); once-monthly injections of 117 mg (deltoid IM or gluteal IM) on days 36 and 64.
  • PBO, n=164
    • Mean duration of INVEGA SUSTENNA and PBO exposure was 87 and 50 days, respectively.
  • The overall incidence of EPS-related TEAEs for the INVEGA SUSTENNA and PBO groups were 23.3% and 12.8%, respectively.
  • The most frequently reported EPS-related TEAEs (≥2% either treatment group) for INVEGA SUSTENNA vs PBO: EPS disorders (10.1% vs 4.9%), akathisia (5.0% vs 1.8%), tremor (2.5% vs 1.2%) and dystonia (2.5% vs 0.6%)
  • From baseline to endpoint, the Drug-Induced Extrapyramidal Symptoms Scale total score decreased slightly for both treatment groups.
  • Patients using antiparkinsonian medications: INVEGA SUSTENNA: 35.2%; PBO: 29.9%
Rater-Blinded Studies
Alphs et al (2015)17 conducted a 15-month (patients could continue participation up to 15 months regardless of reaching primary endpoint or discontinuation of the randomized study drug), prospective, randomized, OL, event monitoring board (EMB)-blinded, multicenter US study (PRIDE: Paliperidone Palmitate Research In Demonstrating Effectiveness) designed to reflect real-world schizophrenia patients, treatments and outcomes.
  • The clinician and patient reviewed the list of available oAPs (aripiprazole, haloperidol, olanzapine, paliperidone, perphenazine, quetiapine and risperidone) before randomization and could preselect up to 6 from the list based on prior experience.
  • Patients were stratified on the basis of their selection of oAP treatments and randomly assigned to flexibly dosed INVEGA SUSTENNA (78-234 mg) or flexibly dosed oAP therapy.
  • Rates of EPS-related TEAEs for INVEGA SUSTENNA and oAPs, respectively were: akathisia (11.1% vs 6.9%), dyskinesia (2.7% vs 1.4%), dystonia (2.2% vs 2.8%), and Parkinsonism (1.8% vs 1.8%).
Schreiner et al (2014)18 conducted a 24-month, randomized, rater-blinded, prospective, OL, international study (PROSIPAL) comparing treatment outcomes, including time to relapse, among patients receiving oAPs versus INVEGA SUSTENNA.
Mean modal doses of individual APs:
  • INVEGA SUSTENNA (n=352)b: 158.7 mg
  • ARI (n=81): 19.1 mg
  • HAL (n=34): 8.2 mg
  • OLA (n=49): 12.9 mg
  • PALI (n=77): 7.5 mg
  • QUE (n=65): 489.2 mg
  • RIS (n=57): 4.3 mg
  • Results and demographics are reported for the core ITT population (acute phase responders who received at least one dose of study medication and had at least one post-baseline efficacy or safety assessment during the core treatment phase)
  • Most common TEAEs (≥5% of patients in any group) included tremor (INVEGA SUSTENNA: 5.1%, n=18; oAPs: 2.2%, n=8)
Li (2011)19 conducted a 13-week, phase 3, randomized, active-controlled, parallel-group, multicenter, OL, rater-blinded study assessing non-inferiority of INVEGA SUSTENNA to RLAI in Chinese patients with acute schizophrenia (n=452, safety analysis set).
INVEGA SUSTENNA (n=229): Deltoid IM injection on day 1 (234 mg) and day 8 (156 mg) with the optional injection site of the gluteal muscle for days 36 (78 or 156 mg) and 64 (78 to 234 mg).
RLAI (n=223): Gluteal IM injection on days 8 and 22 (25 mg); flexible doses on days 36 and 50 (25 or 37.5 mg); and flexible doses of 25 to 50 mg every 2 weeks thereafter beginning on day 64.
  • Daily oral RIS supplementation occurred during the first 4 weeks (2 mg on day 1 and flexible doses of 1 to 6 mg on days 2 through 28). Additional oral RIS 1 to 2 mg was allowed during the 3-week period after each dosage increase.
  • Akathisia, tremor, restlessness, bradykinesia, and musculoskeletal stiffness were included in the TEAEs experienced by ≥5% of patients in any group.
  • Patients experiencing akathisia: INVEGA SUSTENNA: 13.1% (n=30); RLAI: 19.7% (n=44)
  • Patients experiencing tremor: INVEGA SUSTENNA: 10.5% (n=24); RLAI: 17.9% (n=40)
  • Patients who required anti-EPS medication during the OL period: INVEGA SUSTENNA: 31.4%; RLAI: 46.2%
Cross-Sectional Cohort Study
Zhand et al (2022)20 conducted a crosssectional cohort study in outpatients with schizophrenia who were treated with an LAI (N=92; mean age [SD], 44.0 [14.76] years; [range, 20-79 years]).
The rates of EPS and associated factors were compared among 3 subcategories of LAI antipsychotics:
  • FGA LAIs, n(%):
    • ZUC, 1 (1.08)
    • HAL, 1 (1.08)
    • FPT, 12 (13.04)
  • SGA LAIs, n (%):
    • RLAI, 12 (13.04)
    • INVEGA SUSTENNA, 44 (47.82)
  • Partial Agonist, n (%):
    • Aripiprazole, 22 (23.91)
  • The mean (SD) total ESRS scores were 38 (13.8) for FPT, 48.1 (21.5) for RLAI, 37.6 (20.8) for INVEGA SUSTENNA, and 31.05 (12.7) for aripiprazole. Patients in the HAL and ZUC groups were excluded due to small population size.
  • A significant regression was found in ESRS score by medication type (P=0.019).
  • In the INVEGA SUSTENNA group, 48.78% of patients were on doses above maximum.
  • In the INVEGA SUSTENNA group, the mean (SD) total ESRS score for patients on doses above maximum (n=20) was 38.4 (21.6), for those on average to maximum dose (n=13) was 32 (12.8), and for those on low doses (n=8) was 45.13 (28.5).
Observational Studies
Kuru et al (2026)21 conducted a non-interventional observational mirror-image study in outpatients with schizophrenia who initiated INVEGA SUSTENNA and subsequently transitioned to INVEGA TRINZA (N=43; mean age [SD], 35.16 [11.37] years).
The mean [SD] duration of illness was 8.93 [8.85] years with an average of 2.21 [4.13] hospitalizations and 4.14 [3.26] psychotic episodes.
UKU side effect rating scale scores were compared among patients who received INVEGA SUSTENNA and after they transitioned to INVEGA TRINZA.
Data was collected at baseline, after the fourth dose of INVEGA SUSTENNA, and 4 months after switching to INVEGA TRINZA.
  • The UKU side effect rating scale showed EPS related effects such as hypokinesia (INVEGA SUSTENNA, n=10 [40%]; INVEGA TRINZA, n=8 [32%]) and akathisia (INVEGA SUSTENNA, n=6 [24%]; INVEGA TRINZA, n=5 [20%]).
  • The EPS-related TEAEs among both the groups were hypokinesia, akathisia, tremor, and dystonia.
  • Two patients experienced severe AEs requiring treatment discontinuation (1 rigidity, 1 severe akathisia)
Lazare et al (2025)22 conducted a retrospective chart review study evaluating the incidence of EPS associated with LAI antipsychotics among patients who received aripiprazole lauroxil, INVEGA SUSTENNA or haloperidol between July 2023 and June 2024 (N=276).
EPS medication were defined as the use of benztropine, propranolol, valbenazine, or trihexyphenidyl to treat EPS following administration of an LAI.
The incidence of EPS, documented AIMS scores ≥1, and outcomes among patients appropriately transitioned from oral to injectable antipsychotics compared to those who were not appropriate transitioned were evaluated.
  • The incidence of EPS requiring treatment intervention was 28% (80/276) among patients receiving LAI.
  • The incidence of EPS was 28% (46/160) among patients who received INVEGA SUSTENNA.
  • Documented AIMS scores ≥1 were reported in 3% (5/160) of patients receiving INVEGA SUSTENNA.
  • Among patients receiving aripiprazole lauroxil, aripiprazole monohydrate, and INVEGA SUSTENNA, 3.6% (10/276) had an AIMS score ≥1 but did not receive medication for EPS treatment.
  • The proportion of patients appropriately transitioned from oral to injectable antipsychotics was 79% (127/160) among patients receiving INVEGA SUSTENNA.
SCHIZOAFFECTIVE DISORDER
Fu et al (2015)2,23 conducted an international, long-term, DB, PBO-controlled, randomized-withdrawal study of INVEGA SUSTENNA in patients with schizoaffective disorder.
  • During the 13-week, open-label, lead-in period, patients received INVEGA SUSTENNA (234 mg on day 1 and 156 mg on day 8 in the deltoid muscle, followed by flexible doses of 117-234 mg on day 36 and 78-234 mg on days 64 and 92), as monotherapy (n=320) or as adjunct therapy with a mood stabilizer or antidepressant (n=347).
  • Patients who met predefined stabilization criteria (PANSS total scores ≤70; YMRS and HAM-D-21 scores ≤12) entered the 12-week, open-label, fixed-dose phase, receiving INVEGA SUSTENNA once every 4 weeks, at the final dose received during the lead-in period.
    • The last dose of INVEGA SUSTENNA at the end of the open-label phase was 78 mg in 2.7% of patients, 117 mg in 7.3% of patients, 156 mg in 52.8% of patients, and 234 mg in 37.2% of patients.
  • During the 15-month, DB phase, stable patients were randomized to PBO (n=170) or a fixed dose of INVEGA SUSTENNA (n=164)
    • The INVEGA SUSTENNA dose distribution during the DB phase: 78 mg (4.9%), 117 mg (9.8%), 156 mg (47%) or 234 mg (38.4%) doses.
Open-Label Phase:23 During the 25-week open-label phase, 62.5% of patients experienced a TEAE. TEAEs occurring in ≥5% of patients included akathisia (11.1%) and parkinsonism (6.4%).
  • EPS-related TEAEs occurred in 23.2% of patients.

Double-Blind Phase:2 EPS-related TEAEs occurred in 8.5% and 7.1% of INVEGA SUSTENNA and PBO patients, respectively.
  • EPS-related TEAEs (INVEGA SUSTENNA vs PBO) included: hyperkinesia (3.7% vs 2.9%), Parkinsonism (3.0% vs 1.8%), tremor (1.2% vs 2.4%), dyskinesia (0.6% vs 1.8%) and dystonia (0% vs 1.2%).
  • Anti-EPS medication was utilized by 18.9% and 18.8% of INVEGA SUSTENNA and PBO patients at any time during the DB phase.
Abbreviations: AD, antidepressant; AE, adverse event; AIMS, Abnormal Involuntary Movement Scale; BARS, Barnes Akathisia Rating Scale; CGI-MS, Clinical Global Impression of Movement Severity; CI, confidence interval; DB, double-blind; DG, deltoid IM Inj during period 1 followed by gluteal IM Inj during period 2; EPS, extrapyramidal symptoms; ER, extended release; ESRS, Extrapyramidal Symptom Rating Scale; FGA, firstgeneration antipsychotics; FLU, fluphenazine; FPT, flupentixol; GD, gluteal IM Inj during period 1 followed by deltoid IM Inj during period 2; HAL, haloperidol; IM, intramuscular; inj, injection; ITT, intent-to-treat; LAI, long-acting injection; LOCF, last observation carried forward; mg eq. milligram equivalent; MS, mood stabilizer; NS, not significant; oAP, oral antipsychotic; OL, open-label; OLE, open-label extension; PALI, paliperidone; PBO, placebo; RIS, risperidone; RLAI, risperidone long-acting injection; SANS, Scale for the assessment of negative symptoms; SAPS, Scale for the assessment of positive symptoms; SAS, Simpson-Angus Scale; SD, standard deviation; SGA, second-generation antipsychotics; TD, tardive dyskinesia; TEAE, treatment emergent adverse event; ZUC, zuclopenthixol.
aEPS scales included the AIMS, BARS, and SAS; bMean maintenance dose (fourth injection onwards); 91.5% (322/352) received INVEGA SUSTENNA according to appropriate study protocol dosing schedule.

LITERATURE SEARCH

A literature search of Ovid MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File databases (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 17 July 2026.

Several case reports on movement disorders associated with INVEGA SUSTENNA have been provided for your reference below.24-38

Open-label studies, indirect treatment comparisons and post hoc analyses were not included in this response unless the primary outcome focused on movement disorders observed during use of paliperidone palmitate.

 

References

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