Table 2.
Efficacy, safety, and tolerability assessment and main outcomes of reviewed studies on once-monthly paliperidone palmitate
| Author, year | Efficacy assessment | Safety and tolerability assessment | Efficacy outcomes | Safety and tolerability outcomes | Conclusions |
|---|---|---|---|---|---|
| Hough et al 200917 | PANSS CGI-S |
TEAEs SAS BARS AIMS Medication Preference Questionnaire |
(Efficacy assessments were presented at baseline) | Similar reporting of TEAEs in both injection sites during the last 8 weeks after switching Differences in the deltoid injection site preference between countries and sex |
Local tolerability weekly better with gluteal injections Patients from US countries preferred deltoid site versus non-US, and men preferred deltoid site |
| Hough et al 201018 | PANSS CGI-S PSP |
TEAEs SAS BARS AIMS Laboratory tests |
Time-to-relapse was higher in PP treated schizophrenia patients | Injection-site pain was similar between both groups | Schizophrenia patients receiving PP showed a delay in psychotic relapses and similar tolerability than placebo treated patients |
| Nasrallah et al 201019 | PANSS CGI-S PSP |
SAS BARS AIMS Laboratory tests |
Significant improvement in psychotic symptoms in all PP groups | Similar TEAEs frequencies in PP groups and placebo | All doses of PP were efficacious and well tolerated |
| Pandina et al 201020 | PANSS CGI-S VAS for insomnia |
TEAEs SAS BARS AIMS Laboratory tests Vital signs |
Psychotic symptoms improved significantly in all PP dose groups versus placebo | Injection-site pain and dizziness were the TEAEs most commonly encountered | PP at doses of 25 mg eq, 100 mg eq, or 150 mg eq was efficacious compared to placebo |
| Alphs et al 201121 | PANSS CGI-S PSP |
TEAEs SAS BARS AIMS |
Improvement of psychotic symptoms after receiving 234 mg PP No differences in benzodiazepine use |
TEAEs (most frequently): headache, insomnia, schizophrenia exacerbation, injection site pain, agitation No differences in SAS, BARS and AIMS scores |
Acute treatment with PP is effective and well tolerated for markedly to severely schizophrenia patients |
| Bossie et al 2011a22 | PANSS CGI-S PSP |
TEAEs | Improvement of psychotic symptoms (PANSS) after initiation doses in all PP groups | Injection site pain, headache, and agitation more common in PP versus placebo | Initiation doses of PP in recently diagnosed schizophrenia demonstrated improvement in psychotic symptoms |
| Bossie et al 2011b23 | PANSS Responder rates |
TEAEs | After the day 8 injection, PP groups showed greater improvement than placebo, that continued at day 22 and 36 | No unexpected tolerability findings | Initiation doses of PP were associated with significant improvement in psychotic symptoms by day 8, 22, and 36 |
| Li et al 201124 | PANSS CGI-S PSP |
TEAEs SAS BARS AIMS Laboratory tests Vital signs VAS |
Similar improvement in psychotic symptoms between both groups (PP, RLAI) | TEAEs rates were similar between groups Most frequently reported: akathisia, tremor, and insomnia |
PP demonstrated noninferiority compared to RLAI |
| Pandina et al 201125 | PANSS CGI PSP SDS |
TEAEs SAS BARS AIMS VAS (injection site pain) |
Similar decrease in psychotic symptoms in both groups | Proportion of TEAEs and EPS-related TEAEs similar in both groups | Noninferiority of PP to RLAI was demonstrated in acutely ill schizophrenia patients |
| Coppola et al 201230 | PANSS CGI-S PSP |
TEAEs SAS BARS AIMS |
– | The most frequent TEAEs: nasopharingitis, insomnia, injection-site pain, headache, tachycardia, akathisia, and tremor | Safety results of PP 150 mg eq and other doses were consistent with previous studies |
| Sliwa et al 201231 | – | TEAEs SAS BARS AIMS Prolactin levels |
– | Nasopharingitis rates were higher in chronically ill patients compared to recently diagnosed Amenorrhea higher in recently diagnosed Prolactine levels similar in both groups |
TEAEs associated with prolactin levels were similar in both groups, but higher in recently diagnosed women than chronically ill female schizophrenia patients |
| Fleischhacker et al 201226 | PANSS CGI-S PSP |
TEAEs SAS BARS AIMS GISF |
PP did not show comparable efficacy to RLAI (design dependent) | Insomnia most common adverse event, similar in both groups No unexpected safety signals |
Both treatments showed a similar tolerability |
| Alphs et al 201327 | PANSS CGI-S PSP |
TEAEs | Significant reduction in psychotic symptoms (PANSS, CGI) and functionality (PSP) across all groups | PP: Insomnia, headache, injection-site pain RLAI: insomnia, headache |
Treatment with PP or RLAI contributes to improvement of treatment response and adherence |
| Fu et al 201428 | PANSS CGI-S PSP |
TEAEs SAS BARS AIMS |
Efficacy was similar between PP and RLAI groups | TEAEs rates at week 13 for PP were 54.7% versus 50.3% for RLAI | For the completed study, tolerability after initiation of treatment with PP or RLAI was similar in early diagnosed schizophrenia patients |
| Gopal et al 201429 | – | Schooler-Kane standardized research criteria for TD (AIMS) TEAEs |
– | N=4 studies based on PP N=5 studies based on PER Freq TD (PP) AIMS: 0.12% Freq TD (PER) AIMS: 0.05% Freq TD (PP) TEAEs: 0.18% Freq TD (PER) TEAEs: 0.10% |
TD appears to be similar in both groups (PP and PER) Time of onset of TD was highest in the first month |
| Schreiner et al 201432 | PANSS CGI-S PSP SWN Mini-ICF-APP |
ESRS TEAEs |
64% of patients improved in psychotic symptoms and functionality | TEAEs: mild or moderate Injection-site pain, insomnia, and anxiety (most frequently) | Nonacute symptomatic schizophrenia patients switched to PP showed an improvement in psychotic symptoms |
| Alphs et al 201433 Mao et al 201445 |
Time to first treatment failure Time to first hospitalization PSP CGI-S |
– | Results not published | – | Certain clinical features might be associated with increased risks of arrests (preliminary results, final results not published) |
| Hargarter et al 201534 | PANSS | TEAEs ESRS |
After 6 months, 67% of patients treated with PP achieved ≥30% improvement in psychotic symptoms | TEAEs most frequently reported: injection-site pain and insomnia PP was well tolerated with reductions in ESRS |
PP in acute schizophrenia patients unsuccessfully treated with oral antipsychotics was well tolerated |
| Zhang et al 201535 | PANSS CGI-SCH Hospitalization rates Days spent in hospital |
MSQ TEAEs ESRS-A CGI-SCH |
After 18 months a significant improvement in psychotic symptoms was found in all dimensions of PANSS, CGI-SCH in patients treated with PP Lower rates of hospitalizations and health care services utilization |
TEAEs related to disorders (14.6%): worsening of psychotic symptoms 31% mild–moderate EPS adverse events | PP in patients previously treated with oral antipsychotics seems to be efficacious and well tolerated after 18 months |
Abbreviations: AIMS, Abnormal Involuntary Movement Scale; BARS, Barnes Akathisia Rating Scale; CGI-S, Clinical Global Impression-Severity Scale – Severity; CGI-SCH, Clinical Global Impression-Schizophrenia scale; EPS, extrapyramidal symptoms; ESRS, Extrapyramidal Symptoms Rating Scale; ESRS-A, Extrapyramidal Symptom Rating Scale – Abbreviated; GISF, Global Impression of Sexual Function; Mini-ICF-APP, Mini International Classification of Functionality, Disability and Health Rating for Activity and Participation Disorders; MSQ, Medication Satisfaction Questionnaire; PANSS, Positive and Negative Syndrome Scale; PP, paliperidone palmitate; PSP, Personal and Social Performance Scale; RLAI, risperidone long-acting injectable; SAS, Simpson Angus Scale; SDS, Schedule for Deficit Syndrome; SWN, Subjective Well-being under Neuroleptics Scale; TD, tardive dyskinesia; TEAEs, treatment-emergent adverse events; VAS, Visual Analog Scale.