Efficacy and safety profile of paliperidone palmitate injections in the management of patients with schizophrenia: an evidence-based review

Figures & data

Table 1 Summary of randomized, controlled trials for once-monthly paliperidone palmitate vs placebo

Source (year)	Brief description of study	Follow-up period	Sample size, N	Treatment/intervention	Outcomes
Kramer et al (2010)^Citation24	RCT comparing PP-1M/placeboa	9 weeks	197	PP dosage of 50 or 100 mg eq. received (gluteal) on days 1, 8, and 36 or placebo	• PANSS total scores improved for both doses (P<0.01) vs placebo • Fewer PP-treated (2%) vs placebo-treated (10%) patients discontinued the study due to adverse events • PP-treated patients experienced more parkinsonism than placebo
Nasrallah et al (2010)^Citation25	RCT comparing PP-1M/placebo	13 weeks	518	PP dosage of 25, 50, and 100 mg eq. received (gluteal) on days 1 and 8, then every 4 weeks (ie, on days 36 and 64), or placebo	• All PP dose groups showed significant improvement vs placebo in the PANSS total score (P<0.001) and CGI Severity scores (P≤0.006), but not in the PSP • Incidence of treatment-emergent adverse events was similar between groups, as were changes in parkinsonism and BMI
Gopal et al (2010)^Citation26	RCT comparing PP-1M/placebo	13 weeks	388	PP dosage of 50, 100, or 150 mg eq. received (gluteal) monthly after two initial doses given 1 week apart, or placebo	• Only 30 participants were randomized to the 150 mg eq. dose group, and definitive conclusions could not be drawn from the results of that group • PANSS total change scores were significantly better than placebo only for the 100 mg eq. group (P=0.02) • Both the PP 50 (P=0.004) and 100 mg eq. (P<0.001) groups showed significant improvement in the PSP score vs placebo • Adverse events reported more frequently in the PP groups than with placebo were headache, vomiting, extremity pain, and injection site pain
Pandina et al (2010)^Citation27	RCT comparing PP-1M/placebo	13 weeks	652	PP dosage of 150 mg eq. received (deltoid) on day 1 and dose of 25, 100, or 150 mg eq. on day 8 and then once monthly thereafter, or placebo	• PANSS total improved significantly (P<0.03) in all the PP dose groups vs placebo • Treatment-emergent adverse events that occurred more frequently in the PP group vs the placebo group were injection-site pain (7.6% vs 3.7%), dizziness (2.5% vs 1.2%), sedation (2.3% vs 0.6%), pain in the extremity (1.6% vs 0.0%), and myalgia (1.0% vs 0.0%)
Alphs et al (2011)^Citation28	NA	NA	312	NA	• In post hoc analysis in subgroup (n=312), compared with placebo, PP improved psychotic symptoms by day 4 and after subsequent injections, dose-dependent improvements persisted
Hough et al (2010)^Citation29	Relapse-prevention RCT comparing PP-1M/placebo	Phase I (up to 7 days screening) Phase II (9 weeks OL switching) Phase III (24 weeks OL maintenance) Phase IV (DB) Phase V (OLE)	951 849 681 410 176 (patients receiving PP and placebo, respectively, completed OLE)	NA PP dosages of 25, 50, or 100 mg eq. received after initial PP 50 mg eq. on day 1 and day 8 PP flexi dosages of 25, 50, or 100 mg eq. received for first 12 weeks and for last 12 weeks maintenance dose received PP at the previously established stabilized dose received, or placebo NA	• Time to relapse was significantly delayed for PP (P<0.0001) for the interim (n=312) and final analysis (n=408) • Across the phases, mean weight increased by 1.9 kg for PP while it remained unchanged for placebo patients • The incidence of glucose-related adverse events was low (≤4%) • Injection site tolerability was comparable between groups
Gopal et al (2011)^Citation30	Study reporting on Phase V (OLE) of Hough et al (2010)^Citation29	1 year	288b	PP flexi dosages of 25, 50, 75, or 100 mg eq. received (gluteal) and paliperidone ER 3 mg tablets	• Most frequently reported adverse events were insomnia (7%), worsening of schizophrenia, nasopharyngitis, headache and weight increase (6% each) • Potentially prolactin-related adverse events occurred in 3% of patients, mostly women • EPS were reported in 6% of patients • At end point, investigator-rated redness at the injection site was observed in ≤4% of patients and injection site pain was absent in 82%–87% of patients
Fu et al (2017)^Citation31	RCT comparing PP-1M/placebo	Phase I (25 weeks OL) Phase II (15 months DB relapse prevention)	667 334	Subjects were treated with PP-1M either as monotherapy or in combination with antidepressants or mood stabilizers Stabilized subjects received PP-1M or placebo	• Improvements in all PSP domains were observed during the open-label phase and were maintained during the double-blind phase with PP but not with placebo

Notes:

a Phase 2b study;

b two-hundred and eighty-eight of 388 enrolled patients completed the open-label extension.

Abbreviations: eq., equivalent; RCT, randomized controlled trial; PP, paliperidone palmitate; PP-1M, paliperidone palmitate once-monthly; PANSS, Positive and Negative Syndrome Scale; CGI, Clinical Global Impression Severity Scale; PSP, Personal and Social Performance Scale; EPS, emergent extrapyramidal symptoms; OL, open-label; OLE, open-label extension; DB, double blind; ER, extended-release; BMI, body mass index; NA, not applicable.

Table 2 Summary of comparative randomized, controlled trials for once-monthly paliperidone palmitate

Source (year)	Brief description of study	Follow-up period	Sample size, N	Treatment/intervention	Outcomes
Fleischhacker et al (2012)^Citation32	RCT comparing PP-1M/RLAI-1M	53 weeks	747	Acutely symptomatic patients received PP dosage of 50 mg eq. on days 1 and 8, followed by flexible dosing (25–100 mg eq.) once-monthly, or RLAI 2-weekly, 25 mg on days 8 and 22 followed by flexible dosing (25–50 mg) starting from day 36, with oral risperidone supplementation	• Mean (SD) change from baseline to end point in PANSS total score was −11.6 (21.22) for PP and −14.4 (19.76) for RLAI. • PP’s failure to demonstrate comparable efficacy to RLAI was attributed to the suboptimal initiation dosing regimen which resulted in lower median plasma levels of the active moiety in PP-treated patients.
Pandina et al (2011)^Citation33	RCT comparing PP-1M/RLAI-1M	13 weeks	1,220		• Mean PANSS total score change from baseline to end point decreased similarly in both groups. • PP treatment was noninferior to RLAI. • The tolerability and safety of PP was generally similar to that of RLAI.
Fu et al (2014)^Citation34	Post hoc subgroup analysis in markedly to severely ill subjects drawn from Pandina et al (2011)^Citation33		292	PP dosage received (deltoid) of 150 mg eq. on day 1 and 100 mg eq. on day 8. Flexible dosing of 50 mg or 100 mg eq. (deltoid or gluteal) on day 36 and day 64. Or RLAI dosage received (gluteal) of 25 mg on days 8 and 22; 25 or 37.5 mg on days 36 and 50;	• PANSS total scores improved significantly in both arms from day 4 through to end point.
Fu et al (2014)^Citation35	Post hoc, subgroup analysis in subjects drawn from Pandina et al (2011)^Citation33		334	25, 37.5, or 50 mg on days 64 and 78; and oral supplementation with risperidone on days 1–28	• No significant differences in the mean weight change, most metabolic parameters, or mean efficacy measures were observed.
Li et al (2011)^Citation36	OL RCT comparing PP-1M/2-weekly RLAI	13 weeks	452	PP dosages received (deltoid) of 150 mg eq. on day 1 and 100 mg eq. on day 8, then once-monthly flexible dosages of 50, 100, or 150 mg eq. received (deltoid or gluteal). Or RLAI 2-weekly received (gluteal) of flexi doses of 25, 37.5, or 50 mg, and oral risperidone supplementation at initiation and with RLAI dose increase	• Mean (SD) change from baseline to end point in PANSS total scores was −23.6 (16.28) for the PP group and −26.9 (15.43) for RLAI group. • PP was noninferior to RLAI (least-squares mean difference [95% CI]: −2.3 [−5.20, 0.63]). • The incidence of treatment-emergent adverse events was similar between the two groups. • The most common adverse events were akathisia, tremor, and insomnia.
Koshikawa et al (2016)^Citation37	OL RCT comparing effect of PP-1M/RLAI on social functioning	6 months	30	Patients previously treated with RLAI continued with RLAI or received PP	• The PP-treated patients showed greater degree of total social functioning, independent life competence, and performance as compared to the RLAI group.
Takekita et al (2016)^Citation38	In the same sample as Koshikawa et al (2016),^Citation37 cognitive functioning was assessed				• The results suggested that PP might improve attention and processing speed more than RLAI.
Alphs et al (2016)^Citation39	Pragmatic, OL RCT comparing PP-1M/OA	15 months	444	Monthly injectable PP (78–234 mg) or daily OA	• The mean cumulative function of treatment failure events and institutionalizations differed significantly in favor of PP compared with oral antipsychotics (P=0.007 and P=0.005, respectively).
Kwon et al (2015)^Citation40	OL RCT assessing patient satisfaction with switching from OA to PP-1M	21 weeks	154	Immediate switch group received PP dosages of 150 mg eq. on day 1 and 100 mg eq. on day 8, and for later visits the recommended dose was 75 mg eq. or 25, 50, 75, 100, or 150 mg eq. The delayed switch group was maintained on current OA from days 1–56 and received PP dosages of 150 mg eq. on day 57 and 100 mg eq. on day 64, and for later visits the recommended dose was 75 mg eq. or 25, 50, 75, 100, or 150 mg eq.	• Medication satisfaction improved significantly in both groups, with comparable efficacy and tolerability.
Naber et al (2015)^Citation41	OL RCT comparing PP-1M/AOMa	28 weeks	295	PP dosages of 50–150 mg eq. received per month, or AOM 400 mg	• AOM-treated patients showed significantly greater improvements in the QLS total score (4.67 [95% CI: 0.32, 9.02], P=0.04). • Greater improvements in CGI Severity scale and the Investigator’s Assessment Questionnaire for AOM 400 vs PP. • Common treatment-emergent adverse events in the treatment continuation phase were more frequent with PP vs AOM 400.
McEvoy et al (2014)^Citation42	RCT comparing PP-1M/haloperidol decanoate	24 months	311	PP dosages received (deltoid) of 234 mg on day 1 and 156 mg on day 8, and 117 mg received (deltoid or gluteal) once-monthly thereafter. Haloperidol decanoate dose of 50 mg received (deltoid) on days 1 and 8, 75 mg on days 28 and 56, and 50 mg received (deltoid or gluteal) once-monthly thereafter	• There was no statistically significant difference in the rate of efficacy failure for PP-1M compared with haloperidol decanoate (adjusted hazard ratio: 0.98; 95% CI: 0.65, 1.47). • Forty-nine (33.8%) patients in the PP group and 47 (32.4%) in the haloperidol decanoate group experienced efficacy failure. • Patients in PP group gained weight and those in the haloperidol decanoate group lost weight. • PP patients had higher maximum mean levels of serum prolactin while haloperidol decanoate treated patients had greater increases in global ratings of akathisia.
Rosenheck et al (2016)^Citation43	Cost-effectiveness study conducted in the same cohort as McEvoy et al (2014)^Citation42				• PP-1M was associated with 0.0297 greater quality-adjusted life years over 18 months (P=0.03) but with higher average costs for inpatient and outpatient services and medication compared with haloperidol decanoate (P<0.001).
Schreiner et al (2015)^Citation44	Rater-blinded RCT comparing PP-1M/OA	24 months	715	PP doses of 150 mg eq. received (deltoid) on day 1, 100 mg eq. received (deltoid) on day 8, 75 mg eq. on day 38 (deltoid or gluteal), thereafter 25–150 mg eq. (deltoid or gluteal) or OA	• Time to relapse was significantly longer in the PP-1M (n=352) compared with the oral antipsychotics arm (n=363), with 85% relapse-free survival at 469 days for PP-1M patients vs 249 days for oral antipsychotics patients (P=0.02). • There were significantly fewer relapses in the PP-1M group (14.8% vs 20.9%; P=0.03), representing a 29.4% relative risk reduction. Improvements in functionality were comparable between treatment arms.
Gopal et al (2017)^Citation45	Pooled analysis of two RCTs (PP-1M and PP-3M) assessing predictors of caregiver burden	NA	1,498	NA	• Caregiver burden was significantly improved for patients on prior oral antipsychotics after switching to PP.

Note:

a Phase 3b study.

Abbreviations: eq., equivalent; RCT, randomized controlled trial; PP, paliperidone palmitate; PP-1M, paliperidone palmitate once-monthly; PP-3M, paliperidone palmitate 3-monthly; RLAI, risperidone long-acting injection; AOM, aripiprazole once-monthly; OA, oral antipsychotic; PANSS, Positive and Negative Syndrome Scale; CGI, Clinical Global Impression Severity Scale; QLS, Heinrichs–Carpenter Quality-of-Life Scale; OL, open-label; OLE, open-label extension; NA, not applicable.

Table 3 Summary of observational studies and uncontrolled pragmatic trials with once-monthly paliperidone palmitate

Source (year)	Brief description of study	Follow-up period	Sample size, N	Treatment/intervention	Outcomes
Attard et al (2014)^Citation46	Naturalistic study focusing on factors predicting continuation with PP	1 year	200	NA	• Initiation as an outpatient (P=0.001), being switched from risperidone (P=0.03), and correct initiation dosing (P=0.02) were significantly associated with a lower likelihood of discontinuation.
Hargarter et al (2017)^Citation47	Naturalistic study exploring efficacy, safety, and tolerability of PP-1M initiated shortly after hospital admission	6 weeks	367	NA	• Significant improvements were observed in psychotic symptoms (P<0.0001) and PSP scores (P<0.0001). • Treatment was well tolerated.
Baser et al (2015)^Citation48	Study comparing real-world health care costs and resource utilization between SZ patients treated with PP-1M and OA	NA	335	NA	• Patients treated with PP had lower inpatient costs and admission rates, although total health care costs were not significantly different.
Bressington et al (2015)^Citation49	Retrospective mirror-image observational study assessing the effects of PP-1M on acute inpatient hospitalization rates	≥1 year	66		• The mean number of acute admissions fell from 0.86 in the year before PP initiation to 0.23 in the following year (P=0.001).
Doshi et al (2015)^Citation50	Observational, claims-based study examining frequency and duration of concurrent oral prescriptions in patients receiving long-acting injectable formulations of antipsychotics (first and second generation) with a recent history of nonadherence and hospitalization for SZ	NA	340	NA	• The lowest rate of concurrent oral prescribing (58.8%) was found with PP, whereas the highest rate was with RLAI (88.9%).
Schreiner et al (2014)^Citation51	OL study assessing tolerability, safety, and efficacy of flexible doses of PP-1M in a subset of nonacute but symptomatic SZ patients previously unsuccessfully treated with OA	6 months	593	PP dose received (deltoid) of 150 mg eq. on day 1 and 100 mg eq. on day 8. Thereafter, patients received (either deltoid or gluteal) PP dose of 50–150 mg eq. on days 38, 68, 98, 128, and 158.	• PANSS total scores decreased from 71.5 (14.6) at baseline to 59.7 (18.1) at end point (P<0.0001). • PSP score improved significantly from baseline to end point (P<0.0001).
Schreiner et al (2015)^Citation52	In subset of Schreiner et al (2014)^Citation51 sample (ie, patients who switched to PP-1M after unsuccessful treatment with RLAI or conventional depot antipsychotics)		231		• Significant reductions in PANSS total score were observed after switching (P=0.01).
Hargarter et al (2015)^Citation53	In subset of Schreiner et al (2014)^Citation51 sample (ie, patients with acute symptoms of SZ following switching from previously unsuccessful treatment with oral antipsychotics who were switched to PP-1M)		212		• Significant improvements in PANSS total score were observed from day 8 onwards (P<0.0001). • PP was also associated with significant improvements in secondary measures of symptom severity, subjective well-being, medication satisfaction, illness-related disorders of activity and participation, and patient functioning (P<0.0001). • PP was generally well tolerated, with significant reductions in Extrapyramidal Symptom Rating Scale total score (P<0.0001).
Zhao et al (2017)^Citation54	OL study evaluating safety and efficacy of PP-1Ma	25 weeks	353	PP dose of 150 mg eq. received (deltoid) on day 1 and 100 mg eq. received (deltoid) on day 8. Thereafter, patients received (either deltoid or gluteal) flexi doses of 75, 100, or 150 mg eq.	• PANSS total scores improved significantly (P<0.0001), as did PSP scores (P<0.0001). • Most frequently reported emergent adverse events were extrapyramidal disorder (15.3%), akathisia (10.5%), blood prolactin increase (8.8%), and insomnia (5.4%). • Eight deaths were reported, including four completed suicides.
Lafeuille et al (2015)^Citation55	A retrospective study comparing data on re-hospitalization patterns and associated institutional costs after inpatient treatment with PP-1M or OA	6–12 months	45 625	NA	• In the first 12 months after hospital discharge, the risk of rehospitalization and emergency room use was significantly lower in the PP-1M cohort than in the oral antipsychotic cohort (P<0.0001). • Institutional costs during the first 6 months after discharge were significantly lower in the PP-1M cohort (P<0.0001).
Montalvo et al (2013)^Citation56	Prospective observational study assessing effect of switching from RLAI to PP-1M on sexual function and prolactin levels in patients with psychosis who developed hyperprolactinemia on RLAI and who were then switched to PP	3 months	11	NA	• There was a significant decrease in serum prolactin levels (P=0.04) and a fourfold reduction in clinically significant sexual dysfunction.
Morrato et al (2015)^Citation57	Retrospective, observational cohort study using patient claims data comparing effectiveness evidence for PP-1M vs atypical OA	NA	NA	NA	• Emergency room visits and hospitalization rates were lower in PP-1M patients, although hospitalizations did not achieve statistical significance.
Taylor and Olofinjana (2014)^Citation58	Observational study patients prescribed PP in normal practice were followed up	1 year	200	NA	• After 1 year, 65% of patients were still receiving PP. • The number of admissions to hospital in the year following PP initiation was 0.49/patient compared with 0.69/patient/year for the 3 years before initiation (P=0.0001). • The median number of bed days for the 3 years before PP initiation was 21.50/year and in the year following PP initiation, it was 0.
Taylor et al (2016)^Citation59	Observational study of patients treated with PP-1M	2 years	300	NA	• About 38.7% completed 2 years of continuous treatment and a further 7.6% patients discontinued PP but restarted after >2 months. • Prior treatment with risperidone reduced the risk of discontinuation by 39% (P=0.004) and having treatment initiated as an outpatient by 49% (P=0.001). • The risk of discontinuation was increased by 63% when the reason for prescribing PP was poor tolerability of prior treatment (P=0.028).
Taylor et al (2016)^Citation60	A part-prospective mirror-image study examining outcomes of patients receiving PP-1M	2 years prior to PP-1M initiation and 2 years after initiation	225	NA	• At study end point, 41.8% of patients were still receiving PP-1M. • The number of admissions fell from 1.80 in the 2 years before starting PP-1M to 0.81 in 2 years following initiation or discharge (P<0.001). • Total bed days were reduced from 79.6 in the 2 years before to 46.2 in the 2 years after initiation or discharge (P<0.001).
Voss et al (2015)^Citation61	Study assessing elapse risk following switch from RLAI to PP-1M vs a switch from RLAI to OA	NA	319	NA	• Patients who switched from RLAI to PP had fewer events (hospitalization or emergency room visit) (26 vs 32), longer time to an event (mean 70 vs 47 days), and lower risk of relapse (P=0.02) compared with those who switched from RLAI to oral antipsychotics.
Whale et al (2015)^Citation62	Naturalistic study assessing patients who initiated PP-1M	12 months	179	NA	• About 60% of patients continued PP-1M beyond 12 months. • SZ diagnosis, fewer inpatient days after initiation, dose adjustment up or down, and a higher maintenance dose were associated with treatment continuation.
Zhang et al (2015)^Citation63	OL noncomparative study assessing patients with recent-onset SZ who were unsatisfactorily treated with previous OA switched to flexible doses of PP-1M	18 months	521	NA	• PANSS total scores improved significantly (P<0.0001). • There were greater improvements among patients with more severe symptoms. • In a mirror analyses subset (n=474), PP significantly reduced mean number of hospitalization days/person/year as well as percentage of patients requiring hospitalization in past 12 months (P<0.0001). • Adverse events (≥15%) were EPS (31.3%), injection site pain (18.6%), and insomnia (15.2%).
Pesa et al (2017)^Citation64	Retrospective claims-based analysis of Medicaid patients with SZ comparing all-cause health care utilization and costs between patients treated with PP-1M vs atypical OA	12 months	1,444	NA	• PP-1M patients vs patients assigned to the atypical OA cohort, were less likely to discontinue treatment (30.6% vs 39.5%, P<0.001) or switch to a new therapy (21.6% vs 27.7%, P=0.007) and had fewer inpatient visits (5.0 vs 7.9, P<0.001), lower mean hospitalization days (15.0 vs 27.7 days, P<0.001), and inpatient costs (US$5,060 vs US$10,880, P=0.001). • Pharmacy costs were significantly higher in the PP-1M cohort (P<0.001), although total costs were not significantly different (P=0.853).
Pilon et al (2017)^Citation65	Study comparing patients with recent-onset SZ on PP-1M vs OA in terms of adherence, health care resource utilization, and Medical aid spending	NA	24,300	NA	• Patients treated with PP-1M had better adherence (P<0.001) and required less use of concomitant psychiatric medications. • Lower medical costs associated with PP-1M outweighed the higher pharmacy costs, with similar total health care costs across the groups.
Emsley et al (2017)^Citation66	Multicenter, retrospective chart review of medical records of adult patients who were newly diagnosed with SZ who had received continuous treatment with PP-1M in naturalistic clinical settings	≥12 months	84	NA	• Of the patients, 79.2% had ≥20% improvement and 47.2% had a ≥50% improvement in PANSS total scores. PSP score improved significantly in 53.3%. • Most adverse drug reactions were of mild or moderate severity.

Note:

a Phase IV study.

Abbreviations: eq., equivalent; PP, paliperidone palmitate; PP-1M, paliperidone palmitate once-monthly; RLAI, risperidone long-acting injection; OA, oral antipsychotic; PANSS, Positive and Negative Syndrome Scale; EPS, emergent extrapyramidal symptoms; OL, open-label; SZ, schizophrenia; NA, not applicable; PSP, Personal and Social Performance Scale.

Table 4 Summary of studies with 3-monthly paliperidone palmitate

Source (year)	Brief description of study	Follow-up period	Sample size, N	Treatment/intervention	Outcomes
Berwaerts et al (2015)^Citation68	RCT comparing PP-3M/placebo	Phase I (3 weeks screening) Phase II (17 weeks flexi dose, OL transition) Phase III (12 weeks OL maintenance) Phase IV (OL DB)	506	NA PP-1M received for 120 days with a dose of 150 mg eq. (deltoid) received on day 1, 100 mg eq. received (deltoid) on day 8, and flexible doses received (deltoid or gluteal) of 50, 75, 100, or 150 mg eq. on days 36 and 64, and on day 92 the same dose as received on day 64 Single dose PP-3M (which is 3.5× stabilized dose of PP-1M received on day 92) received (either deltoid or gluteal muscle) PP-3M doses of 175, 263, 350, or 525 mg eq., or placebo received	• In the preplanned interim analysis, time to relapse was significantly longer in the PP-3M group vs the placebo group (P=0.001), and PANSS total score and factor analysis derived domain score reductions were greater in PP-3M than placebo (P=0.01). • In Phase IIII, the most frequently reported adverse events in the PP-3M vs placebo groups were headache (9% vs 4%), weight gain (9% vs 3%), nasopharyngitis (6% vs 1%), and akathisia (4% vs 1%).
Savitz et al (2016)^Citation69	RCT comparing PP-3M/PP-1M	Phase I (17 weeks screening)	1,016	After Phase I, clinically stable patients were randomized to PP-3M fixed dose of 175, 263, 350, or 525 mg eq. received (deltoid or gluteal), or PP-1M fixed dose of 50, 75, 100, or 150 mg eq. received (deltoid or gluteal) during Phase II	• PP-3M was noninferior to PP-1M insofar as relapse rates were similar in both groups (8% vs 9%), as were PANSS total score changes and PSP score changes. • There were no clinically relevant differences in pharmacokinetic exposure between PP-3M and PP-1M. • Both groups had similar tolerability profiles with weight gain as the most common treatment-emergent adverse event.
Savitz et al (2017)^Citation70	Post hoc analysis assessing rates of symptomatic and functional remission achieved following PP-3M vs PP-1M treatment in the same sample as Savitz et al (2016).^Citation69	Phase II (48 weeks DB)	NA		• In the PP-3M group, 50.3% achieved symptomatic remission vs 50.8% in the PP-1M group. • Functional remission was achieved in 42.5% in the PP-3M group and 43.9% in the PP-1M group.
Savitz et al (2017)^Citation71	Post hoc analysis conducted in subset of sample from Savitz et al (2016).^Citation69		510		• The percentage of patients who relapsed was similar for PP-3M (10.2%) and PP-1M (11.8%) groups, as was symptom reduction.
Weiden et al (2017)^Citation73	Post hoc study evaluating time to relapse following treatment discontinuation with oral paliperidone, PP-1M, and PP-3Ma	NA	449	NA	• Median days to relapse were 58 days for oral paliperidone, 172 days for PP-1M, and 395 days for PP-3M (P<0.0001).

Note:

a Data were drawn from three similarly designed relapse prevention, placebo-controlled RCTs.

Abbreviations: eq., equivalent; RCT, randomized controlled trial; PP-1M, paliperidone palmitate once-monthly; PP-3M, paliperidone palmitate 3-monthly; PANSS, Positive and Negative Syndrome Scale; PSP, Personal and Social Performance Scale; OL, open-label; DB, double-blind; NA, not applicable.

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