Trial Outcomes & Findings for A Study of Relapse Prevention and the Effectiveness of Long-acting Injectable Risperidone and Quetiapine Tablets in the Treatment of Patients With Schizophrenia or Schizoaffective Disorder (NCT NCT00216476)

Last Updated: 2014-04-16

Results Overview

Relapse was defined as meeting any of the predefined criteria (adapted from Csernansky et al., 2002) on 2 consecutive evaluations during treatment, 3 to 5 days apart. The relapse rate in each treatment arm was estimated using the Kaplan-Meier method.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

753 participants

Primary outcome timeframe

Assessed at each visit from the moment the subject was randomized to a treatment arm (baseline visit) until the end of treatment (Week 104 or earlier)

Results posted on

2014-04-16

Participant Flow

Subjects had a diagnosis of schizophrenia or schizoaffective disorder (according to the Diagnostic and Statistical Manual of Mental Disorders - 4th edition \[DSM-IV\]) and were treated with oral risperidone, olanzapine, or conventional oral neuroleptic monotherapy at screening. They were to be symptomatically stable but not optimally treated.

Participant milestones

Participant milestones
Measure	Risperidone LAI Risperidone Long Acting Injectable (LAI) intramuscular injection, dose of 25, 37.5, or 50 mg every 2 weeks	Quetiapine oral Quetiapine, target dose of 300-400 mg twice daily (b.i.d.) or three times daily (t.i.d.)	Aripiprazole oral Aripiprazole, recommended maintenance dose of 10-30 mg once daily (q.d.)
Overall Study STARTED	329	337	45
Overall Study COMPLETED	224	230	28
Overall Study NOT COMPLETED	105	107	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Risperidone LAI Risperidone Long Acting Injectable (LAI) intramuscular injection, dose of 25, 37.5, or 50 mg every 2 weeks	Quetiapine oral Quetiapine, target dose of 300-400 mg twice daily (b.i.d.) or three times daily (t.i.d.)	Aripiprazole oral Aripiprazole, recommended maintenance dose of 10-30 mg once daily (q.d.)
Overall Study Withdrawal by Subject	59	72	9
Overall Study Lost to Follow-up	10	9	1
Overall Study Adverse Event	6	10	1
Overall Study Lack of Efficacy	4	3	0
Overall Study Death	2	0	0
Overall Study Pregnancy	0	1	1
Overall Study Other	0	0	1
Overall Study Refuses Injection	11	0	0
Overall Study No Further Need for Treatment	3	4	1
Overall Study Non-compliance	0	4	1
Overall Study Higher dose/Extra Medication Required	2	0	2
Overall Study Administrative Reasons	1	1	0
Overall Study Protocol Deviation	5	1	0
Overall Study Patient Moved	2	2	0

Baseline Characteristics

A Study of Relapse Prevention and the Effectiveness of Long-acting Injectable Risperidone and Quetiapine Tablets in the Treatment of Patients With Schizophrenia or Schizoaffective Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Risperidone LAI n=329 Participants intramuscular injection, dose of 25, 37.5, or 50 mg every 2 weeks	Quetiapine n=337 Participants oral, target dose of 300-400 mg b.i.d. or t.i.d.	Total n=666 Participants Total of all reporting groups
Age, Continuous	40.6 years STANDARD_DEVIATION 12.48 • n=99 Participants	42.6 years STANDARD_DEVIATION 13.14 • n=107 Participants	41.6 years STANDARD_DEVIATION 12.85 • n=206 Participants
Sex: Female, Male Female	134 Participants n=99 Participants	146 Participants n=107 Participants	280 Participants n=206 Participants
Sex: Female, Male Male	195 Participants n=99 Participants	191 Participants n=107 Participants	386 Participants n=206 Participants
Race/Ethnicity, Customized Caucasian	320 participants n=99 Participants	330 participants n=107 Participants	650 participants n=206 Participants
Race/Ethnicity, Customized Oriental	1 participants n=99 Participants	2 participants n=107 Participants	3 participants n=206 Participants
Race/Ethnicity, Customized Hispanic	2 participants n=99 Participants	0 participants n=107 Participants	2 participants n=206 Participants
Race/Ethnicity, Customized Black	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Race/Ethnicity, Customized Arab	5 participants n=99 Participants	4 participants n=107 Participants	9 participants n=206 Participants
Race/Ethnicity, Customized Pakistani	0 participants n=99 Participants	1 participants n=107 Participants	1 participants n=206 Participants
Body Mass Index (BMI)	27.6 kg/m2 STANDARD_DEVIATION 5.23 • n=99 Participants	27.0 kg/m2 STANDARD_DEVIATION 5.32 • n=107 Participants	27.3 kg/m2 STANDARD_DEVIATION 5.28 • n=206 Participants
Weight	80.4 kg STANDARD_DEVIATION 16.93 • n=99 Participants	79.0 kg STANDARD_DEVIATION 17.75 • n=107 Participants	79.7 kg STANDARD_DEVIATION 17.35 • n=206 Participants

PRIMARY outcome

Timeframe: Assessed at each visit from the moment the subject was randomized to a treatment arm (baseline visit) until the end of treatment (Week 104 or earlier)

Population: Efficacy analysis set, defined as all subjects who received at least 1 dose of study medication and who had at least 1 efficacy assessment after baseline. This excluded 2 subjects of the risperidone LAI arm and 11 of the quetiapine arm.

Outcome measures

Outcome measures
Measure	Risperidone LAI n=327 Participants intramuscular injection, dose of 25, 37.5, or 50 mg every 2 weeks	Quetiapine n=326 Participants oral, target dose of 300-400 mg b.i.d. or t.i.d.	Aripiprazole oral Aripiprazole, recommended maintenance dose of 10-30 mg once daily (q.d.)
Mean Relapse Free Period(Risperidone LAI Versus Quetiapine)	607 days Standard Deviation 11.4	533 days Standard Deviation 15.6	—

SECONDARY outcome

Timeframe: Assessed at each visit from the moment the subject was randomized to a treatment arm (baseline visit) until the end of treatment (Week 104 or earlier)

As for risperidone and quetiapine, relapse was defined as meeting any of the predefined criteria (adapted from Csernansky et al., 2002) on 2 consecutive evaluations during treatment, 3 to 5 days apart. Since aripiprazole was new on the market at the time the study was conducted, this aripiprazole analysis was exploratory.

Outcome measures

Outcome measures
Measure	Risperidone LAI n=44 Participants intramuscular injection, dose of 25, 37.5, or 50 mg every 2 weeks	Quetiapine oral, target dose of 300-400 mg b.i.d. or t.i.d.	Aripiprazole oral Aripiprazole, recommended maintenance dose of 10-30 mg once daily (q.d.)
Mean Relapse Free Period (Exploratory/Aripiprazole)	314 days Standard Error 20.4	—	—

SECONDARY outcome

Timeframe: Assessed at each visit from the moment the subject was randomized to a treatment arm (baseline visit) until the end of treatment (Week 104 or earlier)

Population: Efficacy analysis set, defined as all subjects who received at least 1 dose of study medication and had at least 1 efficacy assessment after baseline. This excluded 2 subjects of the risperidone LAI, 11 of the quetipaine, and 1 of the aripiprazole arm. One additional subject in each the risperidone LAI and quetiapine arm did not have PANSS data.

The neuropsychiatric symptoms of schizophrenia were assessed by means of the 30-item PANSS scale. The PANSS scale provides a total score (sum of the scores of all 30 items) and scores for 3 subscales, i.e., the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items). Each item of the scale is to be scored on a scale of 1 (absent) to 7 (extreme).

Outcome measures

Outcome measures
Measure	Risperidone LAI n=326 Participants intramuscular injection, dose of 25, 37.5, or 50 mg every 2 weeks	Quetiapine n=325 Participants oral, target dose of 300-400 mg b.i.d. or t.i.d.	Aripiprazole n=44 Participants oral Aripiprazole, recommended maintenance dose of 10-30 mg once daily (q.d.)
Change From Baseline to Endpoint in Total Positive and Negative Syndrome Scale (PANSS) Score	-9.3 units on a scale Standard Deviation 25.65	-1.1 units on a scale Standard Deviation 26.28	-7.7 units on a scale Standard Deviation 27.99

SECONDARY outcome

Timeframe: Assessed at each visit from the moment the subject was randomized to a treatment arm (baseline visit) until the end of treatment (Month 24 or earlier)

Population: Efficacy analysis set, defined as all subjects who received at least 1 dose of study medication and had at least 1 efficacy assessment after baseline. This excluded 2 subjects of the risperidone LAI arm, 11 of the quetipaine arm, and 1 of the aripiprazole arm. One additional subject in the risperidone LAI arm did not have CGI data.

The 7-point CGI scale of Severity (CGI-S) was used to assess the severity of a subject's psychotic condition (0= normal, not at all ill, 1= borderline, etc. and 6= among the most extremely ill subjects).

Outcome measures

Outcome measures
Measure	Risperidone LAI n=326 Participants intramuscular injection, dose of 25, 37.5, or 50 mg every 2 weeks	Quetiapine n=326 Participants oral, target dose of 300-400 mg b.i.d. or t.i.d.	Aripiprazole n=44 Participants oral Aripiprazole, recommended maintenance dose of 10-30 mg once daily (q.d.)
Change From Baseline to Endpoint in Clinical Global Impression Scale (CGI) Score	-0.3 units on a scale Standard Deviation 1.25	0.1 units on a scale Standard Deviation 1.24	-0.1 units on a scale Standard Deviation 1.32

SECONDARY outcome

Timeframe: Assessed at the moment the subject was randomized to a treatment arm (baseline visit) and after 1, 3, 6, 12, 18, and 24 months of treatment

Population: Efficacy analysis set, defined as all subjects who received at least 1 dose of study medication and had at least 1 efficacy assessment after baseline. This excluded 2 subjects of the risperidone LAI, 11 of the quetipaine, and 1 of the aripiprazole arm. An additional 32, 32, and 2 subjects in the respective arms did not have SF-12 data.

Quality of life was assessed by means of the 12-item SF-12® survey. Two parameters, i.e., PCS (physical component summary) and MCS (mental component summary) were calculated. Both components scores range from 0 to 100 with higher scores indicating better QOL.

Outcome measures

Outcome measures
Measure	Risperidone LAI n=295 Participants intramuscular injection, dose of 25, 37.5, or 50 mg every 2 weeks	Quetiapine n=294 Participants oral, target dose of 300-400 mg b.i.d. or t.i.d.	Aripiprazole n=42 Participants oral Aripiprazole, recommended maintenance dose of 10-30 mg once daily (q.d.)
Change From Baseline to Endpoint in Short-Form Health Survey 12 (SF-12) Scores PCS score	2.1 units on a scale Standard Deviation 9.04	1.0 units on a scale Standard Deviation 9.31	2.4 units on a scale Standard Deviation 10.36
Change From Baseline to Endpoint in Short-Form Health Survey 12 (SF-12) Scores MCS score	3.2 units on a scale Standard Deviation 10.43	2.7 units on a scale Standard Deviation 10.88	4.9 units on a scale Standard Deviation 12.10

Adverse Events

Risperidone LAI

Serious events: 63 serious events

Other events: 201 other events

Deaths: 0 deaths

Quetiapine

Serious events: 77 serious events

Other events: 213 other events

Deaths: 0 deaths

Aripiprazole

Serious events: 7 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

EMEA Medical Affairs Director Psychiatry

Janssen Cilag European Medical Affairs

Phone: +34 91 7228043

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Risperidone LAI n=329 participants at risk Risperidone Long Acting Injectable (LAI) intramuscular injection, dose of 25, 37.5, or 50 mg every 2 weeks	Quetiapine n=337 participants at risk oral Quetiapine, target dose of 300-400 mg twice daily (b.i.d.) or three times daily (t.i.d.)	Aripiprazole n=45 participants at risk oral Aripiprazole, recommended maintenance dose of 10-30 mg once daily (q.d.)
Psychiatric disorders Anxiety	11.9% 39/329 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	8.9% 30/337 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	15.6% 7/45 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.
General disorders Asthenia	0.61% 2/329 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	3.3% 11/337 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	6.7% 3/45 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.
Psychiatric disorders Delusion	1.2% 4/329 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	1.2% 4/337 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	8.9% 4/45 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.
Psychiatric disorders Depression	4.6% 15/329 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	4.7% 16/337 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	6.7% 3/45 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.
Nervous system disorders Dizziness	0.61% 2/329 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	4.5% 15/337 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	8.9% 4/45 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.
Nervous system disorders Headache	5.8% 19/329 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	4.7% 16/337 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	11.1% 5/45 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.
Endocrine disorders Hyperprolactinaemia	13.1% 43/329 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	1.5% 5/337 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	0.00% 0/45 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.
Psychiatric disorders Insomnia	10.9% 36/329 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	9.2% 31/337 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	24.4% 11/45 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.
Gastrointestinal disorders Nausea	0.30% 1/329 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	1.8% 6/337 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	11.1% 5/45 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.
Psychiatric disorders Schizophrenia	1.2% 4/329 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	5.0% 17/337 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	0.00% 0/45 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.
Psychiatric disorders Sleep disorder	2.4% 8/329 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	0.59% 2/337 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	6.7% 3/45 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.
Nervous system disorders Somnolence	1.8% 6/329 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	11.3% 38/337 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	0.00% 0/45 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.
Psychiatric disorders Tension	4.3% 14/329 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	4.2% 14/337 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	6.7% 3/45 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.
Investigations Weight decreased	0.30% 1/329 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	1.8% 6/337 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	6.7% 3/45 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.
Investigations Weight increased	7.0% 23/329 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	5.9% 20/337 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.	4.4% 2/45 • All Adverse Events (AEs) occurring between the first study-related procedure, i.e. screening visit, and 6 weeks after the last injection of risperidone LAI or the last intake of quetiapine or aripiprazole (24 months after baseline) were reported. AEs described hereafter are treatment-emergent AEs, defined as AEs that were new in onset or aggravated in severity following treatment start.