Table 1.

Experimental studies included in the narrative review (N = 11).

Author, Year, Country, and Study Design	Sample Size	Assessment Tool(s)	Main Findings	Study’s Limitations
Miura et al., 2022, Japan Double-blind study and 12-week extension study [34].	289 adult patients with schizophrenia.	Positive and Negative Syndrome Scale (PANSS) subscale scores Clinical Global Impression–Severity Scale (CGI-S) The Calgary Depression Scale for Schizophrenia (CDSS)	Patients reported a mean endpoint (week 12) change from the open-label baseline for lurasidone modal 80 mg/d vs. modal 40 mg/d of −0.5 vs. −0.4 at the CGI-S scale and −0.7 vs. −0.1 at the CDSS score. Patients receiving lurasidone modal 80 mg/d reported greater reductions on the PANSS positive subscale (−3.0 vs. −2.3), PANSS negative subscale (−1.9 vs. −1.7), and global scores (−5.1 vs. −3.8) compared to modal 40 mg/d.	Lack of random allocation to different dosages during the extension phase No patients were treated with a fixed dosage of lurasidone 80 mg/d due to the study design Short follow-up period No statistical test for identifying differences between groups
Iyo et al., 2021, Japan A 6-week, double-blind, placebo-controlled study was enrolled in a 12-week open-label extension study with flexible dosing of lurasidone at 40 or 80 mg/day [41].	289 patients were enrolled in the open-label extension study.	Positive and Negative Syndrome Scale (PANSS) total score Clinical Global Impression–Severity Scale (CGI-S) The Calgary Depression Scale for Schizophrenia (CDSS) European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) EuroQol visual analog scale (EQ-VAS)	Treatment with lurasidone compared to placebo has resulted in a broad range of benefits, including improvements in depressive and cognitive symptoms. Patients reported a significant reduction in clinical sympotmatology, scoring −29.4 (17.6) at the PANSS total score in the double blind and −8.8 (13.3) in the open-label study. The CDSS score was stable. An improvement in quality of life evaluated at EQ-5D-3L was found at week 12. Patients reported an overall mean (SD) increase of 0.097 (0.190) (double-blind study) and 0.028 (0.141) (open-label study). An improvement in quality of life evaluated at the EQ VAS was found, scoring 16.8 (24.1) and 5.3 (18.8) at the double-blind and open-label baselines, respectively.	Short follow-up period Lack of a comparator No statistical test for identifying differences between groups
Patel et al., 2020, USA Post hoc analyses [35].	Patients with schizophrenia were randomized to lurasidone (n = 399) and risperidone (n = 190), of whom 129 and 84 continued into OLE, respectively.	Positive and Negative Syndrome Scale (PANSS) Clinical Global Impression–Severity Scale (CGI-S) Montgomery–Asberg Depression Rating Scale (MADRS)	Patients treated with lurasidone (mean change −0.8, 95% CI: −1.6, 0.0) and risperidone (mean change −2.3, 95% CI: −3.2, −1.3) both reported a reduction in the MADRS total score from baseline to month 12. A statistically significant difference was found between patients treated with lurasidone and with risperidone only at month 12 (p = 0.013).	Exclusion criteria: patients with a previous poor or inadequate response/intolerability to risperidone or with an acute exacerbation of schizophrenia Open-label design Lack of a control group
Mattingly et al., 2020, USA Post hoc analyses [36].	Of the 236 patients who completed the initial 12-month double-blind study, 223 (94.5%) continued into the open-label extension study.	Positive and Negative Syndrome Scale (PANSS) Clinical Global Impression (CGI) Montgomery–Åsberg Depression Rating Scale (MADRS)	After completion of 12 months of double-blind treatment with lurasidone or risperidone, mean change scores were −1.7 and −2.6, respectively.	Open-label design Lack of randomization Lack of active control group Small sample size in the risperidone switch group Exclusion criteria: patients with an acute exacerbation No statistical test for identifying differences between groups
Feng et al., 2020, China Randomized, flexible-dose, double-blind, double-dummy, 6-week non-inferiority study comparing the efficacy and the safety of lurasidone to risperidone [33].	444 patients were screened to obtain an intent-to-treat sample of 384 patients, of whom 54 discontinued treatment prior to 6 weeks.	Positive and Negative Syndrome Scale (PANSS) Positive and Negative Syndrome Scale (PANSS)—positive symptoms subscale Positive and Negative Syndrome Scale (PANSS)—negative symptoms subscale Clinical Global Impression–Severity of Illness (CGI-S) Clinical Global Impression–Improvement scale (CGI-I) The Calgary Depression Scale for Schizophrenia (CDSS) Barnes Akathisia Scale (BAS) Abnormal Involuntary Movement Scale (AIMS) Simpson Angus Scale (SAS)	Patients treated with risperidone compared to lurasidone reported a significant increase in glucose (+1.1 mg/dL vs. −0.3 mg/dL; p < 0.05), serum prolactin (+60.4 ng/mL vs. +3.5 ng/mL; p < 0.001), and body mass index (+0.45 kg/m2 vs. +0.20 kg/m2; p < 0.05). No significant differences were found at BARNES, AIMS, and SAS between patients treated with lurasidone and those treated with risperidone (+0.2 vs. +0.2, p = 0.369; +0.0 vs. +0.0, p = 0.922; +0.5 vs. +0.8, p = 0.098 at week 6).	Exclusion criteria: patients with physical and psychiatric comorbidities Short follow-up (i.e., 6 weeks)
Harvey et al., 2017, USA Post hoc analysis based on data from a previously randomized, double-blind, six-week placebo- and active controlled acute study, followed by a one-year [37].	488 patients with schizophrenia, were randomly assigned to lurasidone 80 mg/d, lurasidone 160 mg/d, quetiapine XR 600 mg/die, or placebo.	Item G12: “impaired insight and judgment” of the Positive and Negative Syndrome Scale (PANSS) Montgomery–Åsberg Depression Rating Scale (MADRS) Quality of Well-Being Scale Self-Administered (QWB-SA) scale	Patients treated with lurasidone reported a significant improvement in “insight and judgment” from acute phase baseline to week 6 (effect size = 0.61 for 160 mg/d vs. placebo, p < 0.001; effect size = 0.58 for 80 mg/d vs. placebo, p < 0.001), as well as those treated with quetiapine XR 600 mg/d (effect size = 0.67 vs. placebo, p < 0.001) compared to patients treated with placebo.	Using the single PANSS-item G12 for measuring insight and judgment
Correll et al., 2016, USA Open-label study [42].	A total of 496 patients were randomized in the core acute study. Patients who completed a 6-week, double-blind (DB), placebo-controlled trial continued in a 22-month, open-label (OL) study during which they received once-daily, flexible doses of lurasidone, 40–120 mg.	Positive and Negative Syndrome Scale (PANSS) Clinical Global Impression– Severity Scale (CGI-S) Montgomery–Åsberg Depression Rating Scale (MADRS)	Patients reported a mean change from DB baseline of −43.6 and −28.4 at the PANSS total score at month 24. A significant reduction in MADRS score was found (10.6 ± 6.7 vs. 11.4 ± 6.09). Treatment with lurasidone was associated with a mean change in weight of +0.4 kg at month 12 and +0.8 kg at month 24. Median change to month 12 and month 24, respectively, was −1.0 and −9.0 mg/dL for total cholesterol; 0.0 and −1.0 mg/dL for LDL; +1.0 and −11.0 mg/dL for triglycerides; and 0.0 and −0.1/% for HbA1c.	Lack of randomization Lack of an active comparator Lack of a double-bind design High attrition rate
Nasrallah et al., 2015, USA Patient-level data were pooled from four similarly designed, double-blind, placebo-controlled, 6-week registration studies of lurasidone (40–160 mg/d) [43].	Adult patients with an acute exacerbation of schizophrenia. N = 1330 patients with acute schizophrenia (N = 898 lurasidone, N = 432 placebo).	Montgomery–Åsberg Depression Rating Scale (MADRS)	At week 6, patients treated with both doses of lurasidone reported a significant reduction of depressive symptoms evaluated at MADRS (8.4) compared to those treated with placebo (10.2) (p < 0.001).	Differences in study design, study duration, severity of depressive symptoms at baseline, and outcome measures used in the pooled analysis
Citrome et al., 2014, USA Open-label, 6-month study [40].	Of the 198 patients who completed the core 6-week study, 149 (75.3%) entered the extension study. Clinically stable, but symptomatic, outpatients with schizophrenia or schizoaffective disorder were switched to lurasidone.	Positive and Negative Syndrome Scale (PANSS) Clinical Global Impression Severity of Illness (CGI-S) scores Calgary Depression Scale for Schizophrenia (CDSS) scores	Patients reported a significant reduction in PANSS total score (−8.2 ± 12.6), in CGI-S score (−0.39 ± 0.85), and in CDSS score (−1.2 ± 4.3).	Short follow-up period (i.e., 6 months) Open-label design Lack of a parallel control group
McEvoy et al., 2013, USA Open-label, 6-month study [44].	244 patients with schizophrenia, randomly allocated to lurasidone 40/40, lurasidone 40/80, and lurasidone 80/80.	Positive and Negative Syndrome Scale (PANSS) Clinical Global Impression– Severity Scale (CGI-S) Calgary Depression Scale for Schizophrenia (CDSS) scores	Significant reductions in depressive symptoms were similar across all randomized groups (p = 0.861).	Short follow-up period (i.e., 6 months)
Loebel et al., 2013, USA Prospective, parallel-group study [45].	Patients with schizophrenia randomly assigned to receive 6 weeks of double-blind treatment with once-daily evening doses of lurasidone (80 mg, 160 mg), QXR (600 mg), or placebo, recently hospitalized for an acute exacerbation of psychotic symptoms.	Positive and Negative Syndrome Scale (PANSS) total and subscale scores Clinical Global Impression Severity of Illness (CGI-S) scores Montgomery–Åsberg Depression Rating Scale (MADRS) Negative Symptom Assessment Scale, subject-rated Medication Satisfaction Questionnaire	Patients treated with both doses of lurasidone and QXR-600 mg reported a significantly greater improvement in depressive symptoms compared with the placebo group at week 6, as assessed with the MADRS. Patients treated with lurasidone 80 mg (−22.2 [1.8]) and 160 mg (−26.5 [1.8]) reported a significant improvement compared with the placebo group (−10.3 [1.8]) (p < 0.001). Patients receiving QXR-600 mg reported a greater reduction in PANSS total score compared to placebo (−27.8 [1.8], p < 0.001). Variation in the PANSS total score was similar for patients treated with lurasidone 160 mg compared to those treated with QXR-600 mg (−26.5 vs. −27.8; p = 1.00).	The use of a fixed-dose design facilitated the assessment of dose–response effects Exclusion criteria: patients with physical comorbidity and using other medications