• Users Online: 706
  • Print this page
  • Email this page

Table of Contents
Year : 2021  |  Volume : 35  |  Issue : 3  |  Page : 132-139

Lurasidone switching in patients with schizophrenia who showed suboptimal effect and/or intolerability to current antipsychotics: A multi-center, open-label, single-arm, flexible dose study

1 Department of Psychiatry, Taipei City Hospital and Psychiatric Center, Taipei; Department of Psychiatry, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan
2 Department of Psychiatry, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan
3 Sumitomo Dainippon Pharma Co, Ltd., Tokyo, Japan

Date of Submission13-Apr-2021
Date of Decision11-Jun-2021
Date of Acceptance12-Jun-2021
Date of Web Publication24-Sep-2021

Correspondence Address:
Katsuhiko Hagi
13-1, Kyobashi 1-Chome, Chuo-ku, Tokyo 104-8356
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/TPSY.TPSY_26_21

Rights and Permissions

Objective: In this study, we intended to evaluate the effectiveness and safety of switching to lurasidone in patients with schizophrenia and to get clinical experiences of real-world practice in those who showed suboptimal therapeutic effect and/or intolerability to lurasidone in Taiwan. Methods: We enrolled adult patients (aged 20–75 years) with schizophrenia who had been receiving antipsychotic medications but still continued to show mild-to-moderate symptoms or intolerability, for switching switch to an open-label lurasidone 40–160 mg daily for six weeks. The primary end point of the study was to assess the time to treatment failure, defined as any occurrence of insufficient clinical response, worsen underlying symptoms, or discontinuation due to adverse events. Secondary efficacy measures of the study included decreased scores in the positive and negative syndrome scale (PANSS) total and the clinical global impression-severity scale.(CGI-S), as well as increased clinical global impression-improvement scale (CGI-I). Safety measures included occurrences of treatment-emergent adverse events (TEAEs), abnormal vital signs, Electrocardiogram (ECG), and laboratory parameters. Results: We enrolled 54 patients with 51 completing the study. One patient terminated early due to adverse events and two patients had insufficient therapeutic efficacy. Mean ± standard deviation (SD) time to treatment failure was 27.7 ± 13.1 days. Mean ± SD changes from baseline to six weeks on PANSS, CGI-S, and were −16.8 ± 14.4, −0.6 ± 0.59, and −1.1 ± 1.0, respectively . The most common TEAE was hyperprolactinemia. Furthermore, body weight was significantly decreased from baseline to the end of the study by 0.83 ± 1.96 kg (p < 0.01). Mean ± SD blood prolactin level also was significantly decreased from baseline to week 6 (48.7 ± 52.8 ng/dL vs. 23.9 ± 57.8 ng/dL, p < 0.001). Conclusion: After switching from another antipsychotic, patients with schizophrenia treated with lurasidone showed a low rate of treatment failure among patients in Taiwan. The safety profile is similar to that in previous published lurasidone studies.

Keywords: adverse events, nonresponse, positive and negative syndrome scale, psychosis

How to cite this article:
Lin SK, Yeh CB, Hagi K. Lurasidone switching in patients with schizophrenia who showed suboptimal effect and/or intolerability to current antipsychotics: A multi-center, open-label, single-arm, flexible dose study. Taiwan J Psychiatry 2021;35:132-9

How to cite this URL:
Lin SK, Yeh CB, Hagi K. Lurasidone switching in patients with schizophrenia who showed suboptimal effect and/or intolerability to current antipsychotics: A multi-center, open-label, single-arm, flexible dose study. Taiwan J Psychiatry [serial online] 2021 [cited 2023 May 29];35:132-9. Available from: http://www.e-tjp.org/text.asp?2021/35/3/132/326576

  Introduction Top

Schizophrenia is a relatively prevalent, chronic, and disabling disorder. Worldwide, an estimated 21 million people have this disorder [1]. For many patients, schizophrenia is a life-long illness characterized by a prodromal phase often beginning during the early adolescent years, with subsequent emergence of psychotic symptoms and chronic need for care. Schizophrenia is associated with a markedly decreased functioning and increased morbidity, ranking among the top 20 causes of disability globally [2],[3],[4],[5],[6],[7]. Compared with persons in the general population, life expectancy for patients with schizophrenia is reduced by about 20 years [8].

Although antipsychotic medications are the cornerstone of schizophrenia treatment, many patients do not show a clinical response to an initial trial of such agents. Among those experiencing a first episode, the findings of meta-analyses have been estimated that 52% of patients meet criteria for a 50% reduced score of the positive and negative syndrome scale (PANSS) [9] or brief psychiatric rating scale during acute phase [10],[11]. But for patients with chronic schizophrenia, only 23% of them have been estimated to meet this criterion [12]. Lower clinical response is also seen among patients with schizophrenia who have a greater severity of illness, show less prominent positive symptoms, or are male in sex [13],[14].

To address lack of response to an initial agent, clinicians often switch to another antipsychotic in the treatment of schizophrenia in their clinical practice [15],[16]. Another reason to consider switching to lurasidone because other second-generation (atypical) antipsychotic agents (such as olanzapine, clozapine, and risperidone) often have more metabolic-related adverse events (weight gain) as well as abnormal glucose and lipid metabolism [17],[18],[19].

Lurasidone is a dopamine-serotonin receptor antagonist as defined in neuroscience-based nomenclature system (www.NbN.ECNP.org). It is currently marketed in the USA, Canada, the European Union, Switzerland, Australia, Brazil, Japan, and Taiwan for the treatment of schizophrenia and bipolar depression. This compound is an attractive choice for consideration after the patients show no response or intolerance to an initial antipsychotic drug because lurasidone has novel binding profile – potent antagonism affinity for dopamine D2 and serotonin 5-HT2A and 5-HT7 receptors, partial agonist affinity at 5-HT1A receptors, and moderate antagonist affinity at α2A and α2C adrenergic receptors [20]. Furthermore, lurasidone has either no or minimal affinity for the 5-HT2C receptors, histamine H1 receptors, and muscarinic M1 receptors that are related to weight gain, metabolic syndrome, or sedation [20]. In the treatment of schizophrenia, clinical trials have shown that lurasidone (20–160 mg/day) is efficacious relative to placebo in change in positive symptoms, negative symptoms, and total psychopathology and is usually well tolerated with minimal side effects on body weight, as well as glucose and lipid metabolisms [21]. One previous study has also shown the safety and effectiveness of switching to lurasidone after treatment with another antipsychotic among patients with schizophrenia or schizoaffective disorder who were in a nonacute phase of illness [22]. In a six-week flexibly dosed study with lurasidone (40–120 mg/day), lurasidone has been found to have a low rate (11.6%) of treatment failures without clinically relevant adverse changes in patients' body weight, glucose, insulin, lipids, prolactin, or movement disorders.

As lurasidone is a newly available antipsychotic in Taiwan, we intended in this study to evaluate the effectiveness and safety of switching from other antipsychotics to lurasidone among patients with schizophrenia due to insufficient clinical response or poor tolerability and to obtain clinical experiences of real-world practice. Furthermore, the age range for study patients was also extended from 65 to 75 years to obtain efficacy as well as safety and tolerability data on old adult patients with schizophrenia.

  Methods Top

Study participants

This study was a phase IV, open-label, single-arm, flexible dose, six-week study conducted at two sites in Taiwan from January 2018 to September 2019 (ClinicalTrials.gov identifier = NCT03393026). The study protocol was approved by the institutional review board (IRB) at each of the study sites – at the IRB at Tri-Service General Hospital (IRB protocol number = SCPF20L01TW and date of approval = October 25, 2017) and at the IRB at Taipei City Hospital (IRB protocol number = TCHIRB-10611108-E and date of approval = October 28, 2019) – requiring to obtain written informed consents from the patients before the study.

We enrolled study patients aged 20–75 years diagnosed with schizophrenia, based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, who were clinically stable as judged by the investigator for at least four weeks before baseline and in need of a switch from their current antipsychotic treatment due to insufficient clinical response or poor tolerability (side effects, metabolic complications, etc.). To qualify, a clinical global impression-severity (CGI-S) [23] score ≤ 4 (moderately ill or less) was required at both screening and baseline. Excluded from the study participation were patients who had clinically substantial risk of suicide or violent behavior as judged by the investigator and who had a past history of neuroleptic malignant syndrome, water intoxication, paralytic ileus, or dementia-related psychosis, and active pregnancy or nursing. Additional exclusion criteria were those who were receiving treatment with monoamine oxidase inhibitors within 14 days before screening and who were a current or a past participant in an investigational product, marketed compound, or device within one month before signing the informed consent.

Study treatment

All enrolled patients received a flexible once-daily dose of 40–160 mg oral lurasidone for six weeks. The doses of lurasidone could be adjusted per visit at the investigator's discretion. Tablets were taken with food or within 30 minutes after the meal in the evening.

Prohibited drugs during the study were strong CYP3A4 inhibitors and inducers, as well as grapefruit or grapefruit juice. If a moderate CYP3A4 inhibitor was added during the study, the dose of lurasidone was reduced to half of the original dose level. If a patient was receiving a moderate CYP3A4 inhibitor at study initiation, the recommended starting dose of lurasidone was 20 mg/day and the maximum recommended dose of lurasidone was 80 mg/day.

Efficacy assessments

The primary efficacy measure of the study was time to treatment failure. Treatment failure was determined by the investigator's judgment and was defined as any occurrence of the followings such as insufficient clinical response, exacerbation of underlying disease, or discontinuation due to an adverse event. Secondary efficacy measures of the study were the PANSS, the CGI-S, and the clinical global impression-improvement scale (CGI-I) [23]. Efficacy and safety assessments were done by qualified site-based raters who were research psychiatrists. We evaluated the patients with the PANSS and the CGI-S at screening, baseline, and weeks 1, 2, 4, and 6. The CGI-I was also assessed at baseline and weeks 1, 2, 4, and 6.

Safety and tolerability assessments

We recorded spontaneously reported treatment-emergent adverse events (TEAEs) throughout the six-week study period. Additional safety assessments included vital signs, laboratory tests (liver function, renal function, complete blood count, serum creatinine, fasting serum glucose, prolactin, and lipid profile), 12-lead electrocardiogram (ECG), and physical examination (including body weight). Adverse events, monitoring of concomitant medications, vital signs, and physical examination were done at screening, baseline, and weeks 1, 2, 4, and 6. Laboratory tests and ECG were performed at screening and week six.

Statistical analysis

Effectiveness analyses were done on all patients who entered the trial. The safety population included all patients who received at least one dose of study medication (lurasidone). For the primary effectiveness endpoint, time to treatment failure at week 6 was analyzed by Kaplan-Meier method and presented as the number of observations, mean, standard deviation (SD), median, and the 25th and 75th percentiles. Treatment failure was presented by frequency and percentage. We chose time to treatment failure as the primary endpoint instead of PANSS change score because the patient population recruited into the study all met criteria for treatment failure on their previous antipsychotic medication, either due to poor response or poor tolerability. Therefore, success in switching was judged using the same criteria whether switching to lurasidone reduced treatment failure due to lack of efficacy (poor response) or poor tolerability.

For the secondary effectiveness endpoints, we examined the mean change from baseline to week six (last observation carried forward) with the PANSS total score, CGI-S score, and CGI-I score. These data of each modal daily dose were compared to baseline using Wilcoxon signed-rank test. The comparisons between modal daily doses were done using Steel–Dwass test.

For the safety endpoints, including changes in the assessment results of vital signs, ECG parameters, and laboratory tests, we also used paired t-test or Wilcoxon signed-rank test. For safety analysis on physical examinations, shift tables comparing the status (normal, abnormal, or not done) at baseline and at week six were examined.

The differences between groups were considered significant if p-values were smaller than 0.05 (two-sided). We did all statistical analyses with the International Business Machine Statistical Package for the Social Science software version 26.0 (IBM Corp, Armonk, New York, USA).

All TEAEs were coded using the medical dictionary for regulatory activities, summarized by primary system organ class and preferred term. The TEAEs and SAEs incidences were presented as the number and percentage of patients. The severity and relationship to study medication of TEAE/SAE were summarized as well. The incidence of TEAE/SAE and reasons for early withdrawal were described.

For estimating sample size, we assumed a treatment failure rate of 13% along with a treatment failure precision of 9%. This assumed that failure rate was chosen to be slightly higher than that found (7.9%) in the previous lurasidone switch study [22]. Using a one-sided significant level of 0.025, the estimated enrolled number of patients would be at least 54. Incorporating a 13% dropout rate, about 62 patients were planned to be enrolled in the study. Overall, 54 patients were enrolled in this study because of a lower-than-expected attrition.

  Results Top

We screened 59 patients for the study. Five patients failed the screening, leaving a sample of 54 patients enrolled in the trial [Figure 1]. All 54 patients received at least one dose of study medication. Of the enrolled sample, 51 (94.4%) completed the six-week study. Two patients discontinued the study due to an insufficient clinical response, and another one had an adverse event [Figure 2].
Figure 1: Disposition of the study patients.

Click here to view
Figure 2: Time to treatment failure (Kaplan–Meier plot). The sign “+” indicates the time censored. Three patients with treatment failure were due to insufficient clinical response, insufficient clinical response, and adverse event in the above-shown time frame after receiving lurasidone.

Click here to view

[Table 1] lists patients' demographic and clinical characteristics, including the proportion of patients using each preswitch antipsychotic agent and reasons to participate this trial. During the six-week treatment period, 2 (3.7%) patients who received a modal daily dose of 40 mg, 28 (51.9%) 80 mg, 13 (24.1%) 120 mg, and 11 (20.4%) 160 mg, respectively, with a mean ± SD of 94.1 ± 34.9 mg/day.
Table 1: Patient demographics and baseline clinical characteristics in 54 patients with schizophrenia in Taiwan

Click here to view

[Table 2] summarizes the number of treatment failures, reasons for treatment failure, and the time to treatment failure determined using descriptive statistics. Descriptive statistics were applied since the median time to treatment failure could not be determined by Kaplan–Meier plot because < 50% patients experienced treatment failure [Figure 1].
Table 2: Summary of outcome measures in time to treatment failure (n = 54)

Click here to view

[Table 3] describes the most common TEAEs (≥3%). Of 54 enrolled patients, 41 TEAEs were observed in 26 (48.1%) during the six-week study period. Most TEAEs were mild or moderate in severity. Five severe TEAEs were observed in two patients, including 2 events of pneumonia, 1 event of patella fracture, 1 event of urosepsis, and 1 event of posterior reversible encephalopathy syndrome. No life-threatening TEAEs or deaths were observed. All cases of hyperprolactinemia were judged to be mild in severity.
Table 3: Summary of most common treatment emergent adverse events (≥3%)

Click here to view

Significant changes between baseline and week six were observed in several biochemical tests [Table 4]. These included an increase in mean serum creatinine levels and a decrease in the mean serum Mg levels that were judged to be not clinically significant and were possibly related to the patient' ongoing underlying conditions. We observed significant reductions from baseline in the mean serum prolactin levels (about 49% decrease compared to baseline levels), mean total serum cholesterol levels (about 5% decrease compared to baseline levels), and mean serum low-density lipoprotein levels (about 7% decrease compared to baseline levels) at week six [Table 4]. Although the overall mean prolactin serum level was decreased from baseline to endpoint, three patients had serum prolactin elevation with clinical significance.
Table 4: Weight, metabolic variables, and prolactin-mean ± standard deviation change from baseline to last observation carried forward endpoint

Click here to view

Patients with additional clinically significant abnormal changes from baseline to week six included six (11.1%) with abnormal increase of fasting serum glucose levels, three (5.6%) with abnormal increase in LDL, one (2.0%) with an increase in total cholesterol, one (2.0%) with an increase in triglyceride, as well as three (5.6%) with the presence of leukocyte (3/54, 5.56%), one (1.9%) with erythrocytes, and one with occult blood (1/54, 1.85%) in urine analysis. None of the clinically significant abnormal changes in these laboratory test results were judged to be related to the dosing of lurasidone.

As shown in [Table 4], a significant decrease in the mean body weight was observed between baseline and week six

(p < 0.01 ). Physical examination results in most patients were normal during the study period, except that one patient had musculoskeletal and neurological abnormalities related to a lurasidone-related extrapyramidal disorder and one patient had a musculoskeletal abnormality due to a lurasidone-related patella fracture.

The ECG revealed no significant mean change in QTc interval from baseline to week six. One patient had clinically significant abnormalities in the overall interpretation of the 12-lead ECG at baseline and at week six that were possibly related to his ongoing diabetes, underlying hypertension, and cardiovascular conditions (probable left ventricular hypertrophy) during the study period. None of the above ECG abnormalities was related to the lurasidone as judged by the investigators.

On the secondary outcome measures, significant reductions in PANSS (p < 0.001), PANSS positive (p < 0.001), PANSS negative (p < 0.001), PANSS general psychopathology (p < 0.001), CGI-S (p < 0.001), and CGI-I (p < 0.001) scores were observed from baseline to week six [Table 5]. There were significant reduction in the PANSS total score from baseline (p < 0.001) beginning at week 1 and continuing through week 6 [Figure 3]a. CGI-S score was significantly lower than baseline (p < 0.001) beginning at week 2 and continuing through week 6 [Figure 3]b. On the CGI-I, the mean ± SD change from baseline to week six was −1.1 ± 0.95 (p < 0.001). When examined separately by modal daily dose (40 or 80, 120, 160 mg/day), changes from baseline to endpoint were significant (p < 0.01) for each dosage group on the PANSS total score, PANSS-positive scale, PANSS-negative scale, PANSS general psychopathology scale, and CGI-S [Figure 4].
Table 5: Positive and negative syndrome scale and clinical global impressions-severity-mean ± standard deviation and median change from baseline to last observation carried forward endpoint, 95% confidence interval of the mean, within-group P value and effect size (n = 54)

Click here to view
Figure 3: Mean change from baseline in a) PANSS total score and b) CGI-S. Change in scores of PANSS total (upper panel) and CGI-S (lower panel) *p < 0.05; **p < 0.01; ***p < 0.001, significantly different for change from baseline using Wilcoxon signed-rank test or the paired t-test when appropriate. The paired t-test or Wilcoxon signed rank test (if the data strongly indicated a violation of normal assumption) was used to assess the change from baseline. CGI-S, Clinical global impressions-severity of illness scale; PANSS, Positive and negative syndrome scale.

Click here to view
Figure 4: (a) PANSS total, (b) PANSS positive, (c) PANSS negative, (d) PANSS general psychopathology, and (e) CGI-S in mean change from baseline to last observation carried forward (LOCF) endpoint using modal daily dose. *p < 0.05; **p < 0.01; ***p < 0.001, significantly different for change from baseline using Wilcoxon signed rank test or between modal daily doses (MDDs) using Steel–Dwass test. MDDs in (a) were 40 or 80 mg/day (n = 30), 120 mg/day (n = 13), and 160 mg/day (n = 11). MDDs in (b) were 40 or 80 mg/day (n = 30), 120 mg/day (n = 13), 160 mg/day (n = 11). MDDs in (c) were 40 or 80 mg/day (n = 30), 120 mg/day (n = 13), and 160 mg/day (n = 11). MDDs in (d) were 40 or 80 mg/day (n = 30), 120 mg/day (n = 13), and 160 mg/day (n = 11). MDDs in (e) were 40 or 80 mg/day (n = 30), 120 mg/day (n = 13), 160 mg/day (n = 11). ns, not significant; PANSS, positive and negative syndrome scale.

Click here to view

  Discussion Top

In this six-week study, the effectiveness of switching other antipsychotics to lurasidone 40–160 mg/day over six weeks was evaluated by time to treatment failure. More than 90% of patients completed the treatment with lurasidone for six weeks and < 6% of the study population experienced treatment failure. As shown in [Table 2], the median and mean time to treatment failure of lurasidone were 29 and 27.7 days, respectively.

As shown in [Table 5] and [Figure 2], the efficacy assessments using PANSS (p < 0.001) and CGI-S (p < 0.001) showed significantly improved schizophrenia symptoms after dosing with lurasidone 40–160 mg/day for six weeks. Effect sizes were > 1.0 for all efficacy measures (PANSS and CGI-S), suggesting that the observed improvement in efficacy on lurasidone in this treatment population was robust [Table 5]. It is difficult to make cross-study comparisons because the “treatment failure” patients in Taiwanese population are, to our knowledge, a unique dataset. These results suggest that lurasidone can be an effective next treatment option for patients with schizophrenia who either fail to have an adequate clinical response or have problems with tolerability to a different antipsychotic.

As shown in [Figure 1], the low rate (5.6%) of treatment failures was found. This finding here is similar to the rate (7.9%) found in a previous study that switched clinically stable (for at least eight weeks) patients with schizophrenia from another atypical antipsychotic to six weeks of lurasidone treatment [22]. As shown in [Figure 2], the time to treatment failure was longer in the present study (median = 29 days) compared to the previous study (median = 21 days). This difference may be related to the different dose ranges of lurasidone used in the two studies (40–160 mg/day in the current study; 40–120 mg/day in the previous study).

After being switched from one of non-lurasidone antipsychotics, our study participants [Table 2] were found that lurasidone 40–160 mg/day for six weeks was well tolerated. Only one of 54 patients had treatment failure due to intolerability. [Table 3] lists top five most common TEAEs including hyperprolactinemia, pneumonia, weight decrease, weight increase, and extrapyramidal symptoms. All lurasidone-related TEAEs had been previously reported in lurasidone package insert or related to the symptoms of underlying schizophrenia. The overall safety profile of lurasidone in this study was generally consistent with the findings from previous studies, and no new safety concerns were identified. As in previous studies of lurasidone, there was minimal or no effect on body weight, metabolic parameters, or QTc interval [24],[25]. Although the incidence of hyperprolactinemia as a TEAE in this study was 16.7% [Table 2], this result cannot be compared directly with previous studies because different thresholds of prolactin elevations were in the current study versus those in previous studies. For the sample as whole, a significant decrease (p < 0.01) in serum prolactin levels (−23.9 ± 57.9 ng/mL) was seen at week six compared to baseline levels [Table 3].

In the Clinical Antipsychotic Trial of Intervention Effectiveness study, investigators found that some differences among antipsychotics (olanzapine, quetiapine, risperidone, and ziprasidone) exist in time to discontinuation among patients who discontinued their previous antipsychotic due to lack of efficacy but that no differences between agents are shown in that the study for patients who discontinued due to intolerability [26]. One important factor in choosing a second antipsychotic for clinically unstable patients therefore is the overall safety profile. Given the high association of metabolic syndrome with the patients with schizophrenia [27],[28], and the potential exacerbation of metabolic syndrome by certain antipsychotics [17], consideration should be given to choosing an agent with minimal or no impact on metabolic parameters. A substantial reduction in the economic burden of diabetes and hyperglycemia has been estimated for use of lurasidone in the treatment of schizophrenia compared to other atypical agents (olanzapine, risperidone, quetiapine XR) [29]. Metabolic syndrome is not only a significant risk factor for cardiovascular disease but also can contribute to the cognitive impairment found in schizophrenia [30]. Such cognitive impairments are associated with poor functional outcomes in schizophrenia and are minimally improved by antipsychotic agents [31]. These factors reinforce the clinical consideration of lurasidone as an option for patients showing insufficient clinical response or lack of tolerability to another antipsychotic because lurasidone was found to have good tolerability [Table 3] and [Table 4] and low treatment failure rate [Table 2] in this study.

In the previous lurasidone switch study [22], 70.9% of patients received a modal daily dose of 40 or 80 mg/day and 29.2% received a modal daily dose of 120 mg/day. Treatment was more aggressive in the current study [Figure 4], with 55.6% receiving a modal daily dose or 40 or 80 mg/day, 24.1% receiving 120 mg/day, and 20.4% receiving 160 mg/day. Despite the higher doses in the current study, treatment failure due to adverse events occurred for only one patient over the course of six weeks of lurasidone treatment.

Study limitations

  • Treatment was open-label and the study contained no placebo or active comparator groups. The strength of evidence from an open-label study without active comparator group is not as strong as that from a double-blind comparative study.
  • Because of the lack of a placebo control group, improvements in symptoms over the course of six weeks might be attributable to the effects of time rather than a specific drug effect.
  • The study duration was short (six weeks). A more extended time period is needed to evaluate relapse and the possibility of any longer-term safety concerns.
  • The study design limited study entry to patients who were treatment failures, nonetheless they were clinically stable. This study entry requirement may have limited the generalizability of the study results due to excluding more severe patients with acute exacerbation of schizophrenia on their preswitch antipsychotic medication. The clinical stability may have also contributed to an overestimate of the effectiveness of lurasidone as a switching treatment option.
  • The study was done only in Taiwan. Therefore, the study results might limit the generalizability of the results to other clinical populations or other clinical settings.


This study demonstrated that switching adult patients previously treated with another antipsychotic for schizophrenia to lurasidone can be accomplished with very few treatment failures over the course of six weeks. A six-week treatment of lurasidone 40–160 mg/day was safe and well-tolerated with minimal effects on weight and metabolic parameters and improvement in symptoms of schizophrenia.

  Acknowledgments Top

Medical writing support was provided by Edward Schweizer of Paladin Consulting Group, Inc. (Princeton, New Jersey, USA) and was funded by Sumitomo Dainippon Pharma Co, Ltd., Tokyo, Japan. The authors thank the patients, family members, site investigators, coordinators, study monitors, data managers, and data analysts who contributed to the study.

  Financial support and sponsorship Top

The current study was funded by Sumitomo Dainippon Pharma Co, Ltd., Tokyo, Japan.

  Conflicts of Interest Top

S. K. Lin has received grants for conducting clinical trials, and served as consultant, advisor, or CME speaker for the AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen/J&J, Lundbeck, Mitsubishi Tanabe, Novartis, Otsuka, Pfizer, Reckitt Benckiser, Roche, Sanofi, Serviers, and Sumitomo Dainippon. C. B. Yeh has conducted clinical trials and has been a consultant for Sumitomo Dainippon, also a member of executive editorial board of the Taiwanese Journal of Psychiatry, had no rôle in the peer review process or decision to publish this editorial. K. Hagi is a full-time employee of Sumitomo Dainippon Pharma.

  References Top

World Health Organization: Schizophrenia Fact Sheet. Geneva, Switzerland: World Health Organization, 2016.  Back to cited text no. 1
Vos T, Flaxman AD, Naghavi M, et al.: Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2163-96.  Back to cited text no. 2
Tandberg M, Sundet K, Andreassen O, et al.: Occupational functioning, symptoms and neurocognition in patients with psychotic disorders: investigating subgroups based on social security status. Soc Psychiatry Psychiatr Epidemiol 2013; 48: 863-74.  Back to cited text no. 3
Harvey PD: Assessing disability in schizophrenia: tools and contributors. J Clin Psychiatry 2014; 75: e27.  Back to cited text no. 4
Global Burden of Disease Study 2013 Collaborators: Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 386: 743-800.  Back to cited text no. 5
Correll CU, Solmi M, Veronese N, et al.: Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large-scale meta-analysis of 3,211,768 patients and 113,383,368 controls. World Psychiatry 2017; 16: 163-80.  Back to cited text no. 6
Hjorthøj C, Stürup AE, McGrath JJ, et al.: Years of potential life lost and life expectancy in schizophrenia: a systematic review and meta-analysis. Lancet Psychiatry 2017; 4: 295-301.  Back to cited text no. 7
Laursen TM, Nordentoft M, Mortensen PB: Excess early mortality in schizophrenia. Annu Rev Clin Psychol 2014; 10: 425-48.  Back to cited text no. 8
Kay SR, Fiszbein A, Opler LA: The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13: 261-76.  Back to cited text no. 9
Overall JE, Gorham DR: The Brief Psychiatric Rating Scale. Psychol Rep 1962; 10: 799-812.  Back to cited text no. 10
Zhu Y, Li C, Huhn M, et al.: How well do patients with a first episode of schizophrenia respond to antipsychotics: a systematic review and meta-analysis. Eur Neuropsychopharmacol 2017; 27: 835-44.  Back to cited text no. 11
Leucht S, Leucht C, Huhn M, et al.: Sixty years of placebo-controlled antipsychotic drug trials in acute schizophrenia: systematic review, Bayesian meta-analysis, and meta-regression of efficacy predictors. Am J Psychiatry 2017; 174: 927-42.  Back to cited text no. 12
Rabinowitz J, Werbeloff N, Caers I, et al.: Determinants of antipsychotic response in schizophrenia: implications for practice and future clinical trials. J Clin Psychiatry 2014; 75: e308-16.  Back to cited text no. 13
Furukawa TA, Levine SZ, Tanaka S, et al.: Initial severity of schizophrenia and efficacy of antipsychotics: participant-level meta-analysis of 6 placebo-controlled studies. JAMA Psychiatry 2015; 72: 14-21.  Back to cited text no. 14
Covell NH, Jackson CT, Evans AC, et al.: Antipsychotic prescribing practices in Connecticut's public mental health system: rates of changing medications and prescribing styles. Schizophr Bull 2002; 28: 17-29.  Back to cited text no. 15
Lee JS, Yun JY, Kang SH, et al.: Korean medication algorithm for schizophrenia 2019, second revision: Treatment of psychotic symptoms. Clin Psychopharmacol Neurosci 2020; 18: 386-94.  Back to cited text no. 16
De Hert M, Detraux J, van Winkel R, et al.: Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol 2011; 8: 114-26.  Back to cited text no. 17
Leucht S, Cipriani A, Spineli L, et al.: Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013; 382: 951-62.  Back to cited text no. 18
Perez Rodriguez A, Tajima-Pozo K, Lewczuk A, et al.: Atypical antipsychotics and metabolic syndrome. Cardiovasc Endocrinol 2015; 4: 132-7.  Back to cited text no. 19
Ishibashi T, Horisawa T, Tokuda K, et al.: Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity. J Pharmacol Exp Ther 2010; 334: 171-81.  Back to cited text no. 20
Zheng W, Cai DB, Yang XH, et al.: Short-term efficacy and tolerability of lurasidone in the treatment of acute schizophrenia: a meta-analysis of randomized controlled trials. J Psychiatr Res 2018; 103: 244-51.  Back to cited text no. 21
McEvoy JP, Citrome L, Hernandez D, et al.: Effectiveness of lurasidone in patients with schizophrenia or schizoaffective disorder switched from other antipsychotics: a randomized, 6-week, open-label study. J Clin Psychiatry 2013; 74: 170-9.  Back to cited text no. 22
Guy W: ECDEU Assessment Manual for Psychopharmacology Revised. Rockville, Maryland, USA: Department of Health, Education, and Welfare, National Institute of Mental Health, 1976.  Back to cited text no. 23
Javed A, Hogler A, Curtis L, et al.: Practical guidance on the use of lurasidone for the treatment of adults with schizophrenia. Neurol Ther 2019; 8: 215-30.  Back to cited text no. 24
Ng-Mak D, Tongbram V, Ndirangu K, et al.: Efficacy and metabolic effects of lurasidone versus brexpiprazole in schizophrenia: a network meta-analysis. J Compar Effec Res 2018; 7: 737-48.  Back to cited text no. 25
Stroup TS, Lieberman JA, McEvoy JP, et al.: Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. Am J Psychiatry 2006; 163: 611-22.  Back to cited text no. 26
Mitchell AJ, Vancampfort D, Sweers K, et al.: Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders – a systematic review and meta-analysis. Schizophr Bull 2013; 39: 306-18.  Back to cited text no. 27
Vancampfort D, Wampers M, Mitchell AJ, et al.: A meta-analysis of cardio-metabolic abnormalities in drug naive, first-episode and multi-episode patients with schizophrenia versus general population controls. World Psychiatry 2013; 12: 240-50.  Back to cited text no. 28
Rajagopalan K, Guo S, Hernandez L, et al.: Clinical and cost consequences of metabolic effects of lurasidone versus other atypical antipsychotics in schizophrenia. Open Med J 2014; 1: 1-9.  Back to cited text no. 29
Bora E, Akdede BB, Alptekin K: The relationship between cognitive impairment in schizophrenia and metabolic syndrome: a systematic review and meta-analysis. Psychol Med 2017; 47: 1030-40.  Back to cited text no. 30
Millan MJ, Agid Y, Brüne M, et al.: Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov 2012; 11: 14-68.  Back to cited text no. 31


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
   Financial suppor...
   Conflicts of Int...
   Article Figures
   Article Tables

 Article Access Statistics
    PDF Downloaded210    
    Comments [Add]    

Recommend this journal