Durgam 2014.

Methods	Allocation: multinational, randomised. Blindness: double blind, but unclear who is blinded. Duration: 9 weeks duration including 7 days wash out period, 6 weeks treatment period and 2 weeks safety follow up. Settings: inpatients, 65 study centres in the United States, India, Russia, Ukraine, and Malaysia. Design: parallel.
Participants	Diagnosis: schizophrenia (DSM‐IV‐TR). N = 729. Age: mean ˜ 36 years, SD ˜ 10.8 years. Sex: male 502, female 227. Length of illness: mean ˜ 11.6 years, SD ˜ 9.7 years. Inclusion criteria: 18‐60 years old, atients had the diagnosis for at least 1 year, current exacerbation less than 2 weeks' duration, and at least 1 psychotic episode requiring hospitalization/antipsychotic medication change/intervention during the preceding year. PANSS total score between 80 and 120, a score ≥4 (moderate) on at least 2 of 4 PANSS positive symptoms (delusions, hallucinatory behavior, conceptual disorganization, suspiciousness/persecution); CGI‐S rating ≥4; Body mass index (BMI) between 18 and 35. Exclusion criteria: first episode of psychosis; diagnosis of various DSM‐IV‐TR disorders (e.g., schizoaffective, schizophreniform, bipolar I and II); alcohol/ substance abuse/dependence (within 3 months); treatment‐resistant schizophrenia (poor response to ≥2 antipsychotics of adequate dose and duration) or suicidal or homicidal attempt/intent (active or preceding 2 years). Typical treatment‐related, concomitant medication, and medical/physical exclusions were applied.
Interventions	1. Risperidone: 4 mg/d , N = 140. 2. Placebo: once daily, N = 151. 3. Cariprazine low dose: 1.5 mg/d, N = 145*. 4. Cariprazine medium dose: 3 mg/d, N = 146*. 5. Cariprazine high dose: 4.5 mg/d, N = 147*.
Outcomes	Mental state: no clinical response**, PANSS, Negative Symptom Assessment (NSA‐16). Leaving the study early. Global state: Clinical Global Impressions‐Improvement (CGI‐I). Adverse effects***: Treatment‐emergent adverse events (TEAEs). Unable to use: physical examination, laboratory evaluations, vital signs, weight, and 12‐lead ECG.
Notes	*We did not use the data from these groups, as the interventions are not relevant. **defined as the decrease rate of PANSS score < 30% improvement from baseline) ***For the concomitant medications rate reported in this study, we only extracted 2 drugs mentioned in our protocol.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised, no further information. Quote: "A 9‐week, multinational, randomized, double‐blind..." (p.451).
Allocation concealment (selection bias)	Unclear risk	No information available.
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Seventy‐two out of 151 participants left the study early from placebo group, while 39 out of 140 participants left the study early from risperidone group. Intention to treat analysis was used to analyzed the data and sensitivity analysis was also conducted by using mixed effects model for repeated measures.
Selective reporting (reporting bias)	Low risk	All the measured outcomes were reported.
Other bias	Low risk	None obvious.