Assessment of the treatment effectiveness of men with mild and medium degree of erectile dysfunction.

OBJECTIVE: . Aim: To assess the effectiveness of monotherapy and complex treatment of patients with erectile dysfunction depending on its severity. PATIENTS AND METHODS: Materials and Methods: Men with moderate and mild erectile dysfunction took part in the study, who, in turn, were divided into groups, depending on the treatment, with the evaluation of the results of the International Index of Erectile Function (MIEF-15), the state of cavernous hemodynamics and the function of the vascular endothelium before and after treatment. RESULTS: Results: In patients with an average degree of severity, who received complex treatment including a course of low-energy shock wave therapy, against the background of taking sildenafil and L-arginine, the best results were obtained in the quality of erection and increased cavernous blood flow, which positively affected satisfaction with sexual intercourse and overall satisfaction. It has also been proven that the function of the endothelium was improved in patients receiving L-arginine, due to which there was a probable decrease in endothelin-1. A probable improvement of erectile function was obtained in the group of patients with a mild degree who received L-arginine, and there was no statistical difference from the indicators in the group who received sildenafil, which was confirmed by the data of dopplerography. CONCLUSION: Conclusions: Patients with an average degree of erectile dysfunction require comprehensive treatment. The use of L-arginine can be an alternative to phosphodiesterase type 5 inhibitors in the treatment of mild erectile dysfunction.

Adjunctive cariprazine as a novel effective strategy for treating major depressive disorder: A systematic review and meta-analysis.

BACKGROUND: Cariprazine has been approved by the Food and Drug Administration for treating bipolar depression and as an adjunctive treatment for Major Depressive Disorder (MDD). However, it remains unclear about its pharmacological efficacy in treating MDD. Therefore, a meta-analysis was conducted to investigate the adjunctive use of cariprazine in MDD. METHODS: Electronic databases were searched for eligible studies evaluating the efficacy and safety of cariprazine in patients with MDD up to November 15, 2023. The changes in Montgomery-Asberg Depression Rating Scale (MADRS) score and incidence of adverse events (AEs), which represents of efficacy and tolerability, are considered as the main outcomes. RESULTS: A total of 3066 patients with MDD included in all across 5 RCTs. With regard to MADRS score, cariprazine group showed better results than control group (SMD = -0.12, 95% CI -0.19 to -0.04, P = 0.002, 5 RCTs, n = 3066). Cariprazine, meanwhile, improved the MADRS response (RR = 1.19, 95% CI 1.08 to 1.31, P = 0.0004, 5 RCTs, n = 3066). For safety outcomes, statistical difference was observed in AEs (RR = 1.26, 95% CI 1.18 to 1.35, P < 0.00001, 5 RCTs, n = 3077). The suicide ideation and SAEs showed no statistical difference between two groups. CONCLUSION: Cariprazine demonstrated antidepressant effect as an augmentation therapy in treating MDD. Meanwhile, the tolerability of it was acceptable as an adjunctive treatment. However, studies with larger sample sizes are still needed to explore the optimal dosage.

Development of a simple high-performance liquid chromatography-ultraviolet detection method for olaparib in patients with ovarian cancer.

Olaparib is a small-molecule inhibitor of poly(ADP)-ribose polymerase (PARP) used as maintenance therapy for recurrent ovarian cancer and newly diagnosed advanced ovarian cancer after initial chemotherapy. An exposure-toxicity correlation has been reported between the probability of anemia, a common adverse event associated with olaparib, and the steady-state minimum plasma concentration (Cmin) as well as the predicted maximum plasma concentration (Cmax). On the other hand, olaparib exhibits high interpatient variability with regard to the area under the concentration-time curve, Cmax, and Cmin. Therefore, we developed a simple and sensitive assay based on high-performance liquid chromatography with ultraviolet light (HPLC-UV) for the therapeutic drug monitoring of olaparib. The analysis was performed on an octadecylsilyl column with a mobile phase consisting of 0.5% KH2PO4 (pH 4.5) and acetonitrile (71:29, v/v), at a flow rate of 0.8 mL/min. Olaparib and an internal standard (imatinib) were well separated from the co-extracted material, with retention times of 13.6 and 11.5 min, respectively. The calibration curve for olaparib showed linearity over the concentration range of 0.10-10.0 µg/mL (r2 = 0.9998). The intra- and inter- day validation coefficients ranged from 1.79 to 4.13% and 1.37 to 3.55%, respectively. Measurement accuracy ranged from - 6.07 to 3.26%, with a recovery rate of more than 91.06%. The developed method was then applied to evaluate the plasma olaparib concentrations in patients with ovarian cancer. Our findings demonstrate that HPLC-UV is an economical, simple, and sensitive method for clinical application and holds promise for the effective drug monitoring of olaparib during ovarian cancer treatment.

Olaparib maintenance versus placebo in platinum-sensitive non-small cell lung cancer: the Phase 2 randomized PIPSeN trial.

BACKGROUND: Platinum-sensitivity is a phenotypic biomarker of Poly (ADP-ribose) polymerase inhibitors (PARPi) sensitivity in histotypes where PARPi are approved. Approximately one-third of non-small cell lung cancers (NSCLC) are platinum-sensitive. The double-blind, randomized phase II PIPSeN (NCT02679963) study evaluated olaparib, a PARPi, as maintenance therapy for patients with platinum-sensitive advanced NSCLC. METHODS: Chemonaïve patients with ECOG performance status of 0-1, platinum-sensitive, EGFR- and ALK-wild-type, stage IIIB-IV NSCLC were randomized (R) to receive either olaparib (O) maintenance or a placebo (P). The primary objective was progression-free survival (PFS) from R. Secondary objectives included overall survival (OS) and safety. With an anticipated hazard ratio of 0.65, 144 patients were required to be randomized, and approximately 500 patients enrolled. RESULTS: The trial was prematurely terminated because anti-PD(L)1 therapy was approved during the trial recruitment. A total of 182 patients were enrolled, with 60 patients randomized: 33 and 27 in the O and P arms, respectively. Patient and tumor characteristics were well-balanced between arms, except for alcohol intake (33% vs 11% in the O and P arms, respectively, p = 0.043). The median PFS was 2.9 and 2.0 months in the O and P arms, respectively (logrank p = 0.99). The median OS was 9.4 and 9.5 months in the O and P arms, respectively (p = 0.28). Grade ≥3 toxicities occurred in 15 and 8 patients in O and P arms, with no new safety concerns. CONCLUSION: PIPSeN was terminated early after enrollment of only 50% of the pre-planned population, thus being statistically underpowered. Olaparib maintenance did neither improve median PFS nor OS in this patient population.

The prevalence of hepatic and thyroid toxicity associated with imatinib treatment of chronic myeloid leukaemia: a systematic review.

BACKGROUND: Imatinib, a potent inhibitor of targeted protein tyrosine kinases, treats chronic myeloid leukaemia (CML). Data on imatinib-associated changes in hepatic and thyroid functions are limited and conflicting. AIM: To report the prevalence of hepatic and thyroid toxicity associated with the use of imatinib in CML patients. METHOD: Articles for the systematic review were selected from electronic databases (PubMed, CINALH, Web of Science). Readily accessible peer-reviewed full articles in English published 1st January 2000 to 18th July 2023 were included. The search terms included combinations of: imatinib, CML, liver toxicity, hepatic toxicity, thyroid toxicity. Screening of titles, abstracts, full text articles was conducted independently by two reviewers. Inclusions and exclusions were recorded following PRISMA guidelines. Detailed reasons for exclusion were recorded. Included articles were critically appraised. RESULTS: Ten thousand one hundred and twenty-three CML patients were reported in the 82 included studies corresponding to 21 case reports, 2 case series, 39 clinical trials and 20 observational studies were selected. Excluding case studies/reports, 1268 (12.6%; n = 1268/10046) hepatotoxicity adverse events were reported, of which 64.7% were rated as mild grade I & II adverse events, 363 (28.6%) as severe, grade III and IV adverse events; some led to treatment discontinuation, liver transplantation and fatal consequences. Twenty (35.1%) studies reported discontinuation of imatinib treatment due to the severity of hepatic toxicity. Fourteen (8.4%, n = 14/167) thyroid dysfunction adverse events were reported. CONCLUSION: High frequency of mild and severe hepatotoxicity, associated with imatinib in CML patients, was reported in the published literature. Low numbers of mild and manageable thyroid toxicity events were reported.

Real-world outcomes of patients with metastatic endocrine-responsive breast cancer receiving palbociclib-based combinations.

Aim: To describe treatment journey and clinical outcomes after palbociclib initiation in HR+/HER2- breast cancer patients across multiple lines. Materials & methods: Adult patients (n = 559) were identified in a population-based study between January 2018 and June 2020. Results: Median follow-up time was 41.2 months. The starting dose was 125 mg for more than 85% of patients, and a third had dose reduction. Median time on treatment was 30.5 months for palbociclib + aromatase inhibitors for patients that received first-line treatment after metastatic diagnosis, and 12.6 months for palbociclib + fulvestrant across multiple lines, and longer for patients that had a dose reduction during treatment. At 48 months, 59.3 and 27.3% of patients were still alive, respectively. Subsequent lines resulted in median time on treatment of 4.4-7.7 months in both groups. Conclusion: Time on treatment for palbociclib was comparable to data from clinical trials, and follow-up allowed us to examine subsequent treatment after initial treatment failure. Dose reduction was common in the real-world setting and did not adversely affect efficacy.

We used healthcare data from Israel to study the outcomes of adults (mostly women) who had breast cancer that spread (metastatic) and who started treatment with anticancer medications in the form of palbociclib in combination with either aromatase inhibitors (as first treatment after metastatic disease diagnosis) or fulvestrant (after having been treated with a different medication) between January 2018 and June 2020. Patients treated with palbociclib with aromatase inhibitors (52%) were on average 63 years old, and most had medium to high socioeconomic status (63%) and functioned independently (60%). Patients were treated on average for 30.5 months, and just over a third switched to a different treatment after their disease worsened. Four years after starting treatment, 59% of patients were still alive. Patients treated with palbociclib and fulvestrant, after having been treated with a different medication (48%), were on average 66 years old, and 61% had medium to high socioeconomic status and 50% functioned independently. These patients were treated on average for 12.6 months, and over two-thirds switched to a new treatment. Four years after starting this treatment, 27% of patients were still alive. Overall, most patients included in this study started treatment with the recommended dose of palbociclib (125 mg), and a third had to change to a lower dose to continue treatment (probably due to side effects). Clinical trial registration: NCT04671615 (ClinicalTrials.gov).

[Evaluation of the efficiency and safety of the dispersed form of sildenafil (50 mg) in males with erectile dysfunction].

INTRODUCTION: The erectile dysfunction is defined as an inability to achieve or maintain an erection sufficient for sexual intercourse lasting more than 3 months. According to literature, about 90 million men worldwide suffer from erectile dysfunction of different severity. AIM: To evaluate the efficacy and safety of the dispersed form of sildenafil ("Ridzhamp" 50 mg), compared with the standard tablets of sildenafil (50 mg). MATERIALS AND METHODS: The study included 60 men aged 27 to 67 years (average age 40.2 years) with moderate erectile dysfunction (11-15 points according to IIEF-5). In group I (n=30), patients took a dispersible form of the drug sildenafil, 50 mg ("Ridzhamp") 60 minutes before sexual intercourse; in group II (n=30), a standard form of the drug sildenafil was prescribed at a dosage of 50 mg, 60 minutes before sexual intercourse. RESULTS: Positive dynamics according to IIEF-5 score was found in all the study groups. In group I, IIEF-5 score increase by 53.85%, while in group II by 50% (p<0.05). The average onset of erection in group I was 45+/-2.2 min, while in group II it was 51+/-1.9 min. In the main group (group I) one patient (3.33%) complained of persistent headache after taking the drug, and therefore refused the therapy. In the comparison group (group II) one patient (3.33%) reported dyspeptic disorders while taking the drug, 1 patient (3.33%) reported dizziness. All patients in the main group noted the convenience of taking the "Ridzhamp". CONCLUSIONS: Our results indicate the comparable efficiency of the dispersed form of sildenafil (group I) and the standard tablet form of the drug (group II). All patients in the main group (group I) noted a faster onset of erections, as well as the convenience of "Ridzhamp" and the ability to take the drug without water intake.

Therapeutic Appropriateness of Cariprazine in the Management of Schizophrenia: Experts' Opinion using a Delphi Approach.

BACKGROUND: Schizophrenia is a psychiatric disorder whose therapeutic objectives are aimed at reducing symptoms and improving patient's quality of life. First- and second-generation antipsychotics present numerous side effects. Recently introduced in the treatment of schizophrenia, cariprazine has shown to improve positive and negative symptoms as well as cognitive impairment, with good tolerability. OBJECTIVE: To assess the level of consensus among Italian psychiatrists in relation to the use of cariprazine in the treatment of schizophrenia by using the Delphi technique. METHOD: A Delphi study was undertaken between January and July 2022. Two questionnaires were consecutively sent to a panel of 97 psychiatrists from all over Italy, of which 81 actively participated, anonymously, in at least one of the two consultations with a sufficiently high response rate (83%). RESULTS: Broad consensus in terms of the efficacy and safety of cariprazine in the treatment of schizophrenia during all phases of the disorder. The young first-episode schizophrenia patient with or without substance abuse seems to be an excellent candidate for cariprazine therapy. In addition, the lack of side effects makes cariprazine a suitable drug for adult and elderly patients with schizophrenia. However, there is still limited experience with the use of cariprazine, along with little knowledge of the most recent real-life data. CONCLUSION: These results could encourage wider dissemination of evidence-based practices with the final aim of optimizing the clinical use of cariprazine in patients with schizophrenia.

Does drug use affect the efficacy of amisulpride, aripiprazole and olanzapine in patients with schizophrenia spectrum disorders? Results from a pragmatic, randomised study.

OBJECTIVES: Drug use is prevalent in patients with schizophrenia spectrum disorders (SSD) but there is limited knowledge about the influence of drug use on the effectiveness of antipsychotic medication. This secondary explorative study compared the effectiveness of three antipsychotics in patients with SSD, with and without drug use. METHODS: The BeSt InTro multi-centre, head to head, rater-blinded randomised study compared amisulpride, aripiprazole and olanzapine over a 1-year follow-up period. All patients (n = 144) were aged ≥18 years and met the ICD-10 criteria for SSD (F20-29). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The primary outcome was reduction of a PANSS positive subscale score. RESULTS: At baseline, 38% of all patients reported drug use in the last 6 months before inclusion, with cannabis as the main drug (85%), followed by amphetamine-type stimulants (45%), sedatives (26%), hallucinogens (19%), cocaine (13%), opiates (4%), GHB (4%), solvents (4%), analgesics (4%) and anabolic steroids (2%). The predominant pattern was the use of several drugs. There were no significant overall differences in the PANSS positive subscale score reduction for the three studied antipsychotics among patients either with or without drug use. In the drug use group, older patients treated with amisulpride showed a greater PANSS positive subscale score reduction during the treatment period compared to younger patients. CONCLUSION: The current study showed that drug use does not appear to affect the overall effectiveness of amisulpride, aripiprazole and olanzapine in patients with SSD. However, amisulpride may be a particularly suitable choice for older patients with drug use.

Effectiveness of vortioxetine in patients with major depressive disorder and early-stage dementia: The MEMORY study.

BACKGROUND: Depression and dementia are highly prevalent in older adults and often co-occur. This Phase IV study investigated the effectiveness and tolerability of vortioxetine in improving depressive symptoms, cognitive performance, daily and global functioning and health-related quality of life (HRQoL) in patients with major depressive disorder (MDD) and comorbid early-stage dementia. METHODS: Patients (n = 82) aged 55-85 years with a primary diagnosis of MDD (onset before age 55 years) and comorbid early-stage dementia (diagnosed ≥6 months before screening and after onset of MDD; Mini-Mental State Examination-2 total score, 20-24) received vortioxetine for 12 weeks (initiated at 5 mg/day and up-titrated to 10 mg/day at day 8, with flexible dosing thereafter [5-20 mg/day]). The primary endpoint was change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 12. RESULTS: Significant improvement in depressive symptom severity was seen from week 1 onwards (P < 0.0001). At week 12, the least-square mean (standard error) change in MADRS total score from baseline was -12.4 (0.78). Significant improvements in cognitive performance were observed (from week 1 for the Digit Symbol Substitution Test and week 4 for the Rey Auditory Verbal Learning Test). Patients also experienced significant improvements in daily and global functioning, and HRQoL. Vortioxetine was well tolerated. From week 4 onwards, more than 50 % of patients were receiving 20 mg/day. LIMITATIONS: Open-label study. CONCLUSIONS: Vortioxetine demonstrated effectiveness in clinically significantly improving depressive symptoms, cognitive performance, daily and global functioning, and HRQoL in patients with MDD and comorbid early-stage dementia treated for 12 weeks. TRIAL REGISTRATION: ClinicalTrials.gov/ct2/show/NCT04294654.

Study UNICO: Perception of Urologists and Andrologists, in Spain, about the Use of Sildenafil Oral Suspension in Patients with Erectile Dysfunction.

OBJECTIVE: To describe the profile of patients with erectile dysfunction (ED), attending to consultation and satisfaction using sildenafil oral suspension, from the specialist's perception. MATERIALS AND METHODS: This is a nationwide multicenter, epidemiological, descriptive and observational study, with the studied population as the unit of study. Thirty urologists and/or andrologists completed a questionnaire with questions about ED patients' profile attending to their practice, sildenafil oral suspension perception of effectiveness and safeness, and their opinion about patients' satisfaction after sildenafil oral suspension treatment. Aggregate data were collected for the last 6 patients treated or on treatment with sildenafil oral suspension. RESULTS: Overall, 40.9% and 24.9% of patients had moderate or severe ED, respectively. Among the patients, 73.6% were older than 50 years. The disease progression was approximately one year (11.8 months). ED etiology was mostly organic (38.1%) and mixed (31.8%). Cardiovascular comorbidities were present in 57.4%, mental health problems in 16.4% and hormonal disorders in 10.2% of the patients. The main reason for choosing sildenafil oral suspension was the ease of dose adjustment. The specialists considered that 73.4% of the patients responded satisfactorily to treatment. They also rated the perceived effectiveness and safeness of the product as very good or good. CONCLUSIONS: Urologists and andrologists consider that most patients with ED achieve a high degree of satisfaction with sildenafil oral suspension. The main advantage of the treatment is the possibility of adjusting the dose according to patient's needs and circumstances.

Catechin from Anonna senegalensis is a Potential Inhibitor of Erectile Dysfunction: Implication for Its Use in Male Sexual Enhancement.

Erectile dysfunction (ED) is a major challenge for men. The drugs for its treatment are associated with side effects. Hence, in phytomedicinal research, where Anonna senegalensis (A. senegalensis) is a candidate with abundant phytochemicals possessing various pharmacological properties, but the sex-enhancing phytochemical is elusive in the literature. This study aimed to understand the molecular interaction of its potent molecule mediating male sexual enhancement. A library of 69 compounds from A. senegalensis was docked against the ED-targeted proteins. Sildenafil citrate was used as the reference standard. Thereafter, the lead compound was screened for drug-likeness by applying the Lipinski rule of 5 (RO5), pharmacokinetic properties, and bioactivity using SwissADME and Molinspiration web servers, respectively. The results show catechin as the lead phytochemical compound with a stronger binding affinity for most of the proteins of ED. Also, catechin demonstrates good compliance with the RO5, great pharmacokinetic profiles, and could be said to be a polypharmacological molecule with good bioactivity scores. The research findings unravel the potential of catechin (a phytochemical belonging to the flavonoids class) from A. senegalensis leaf as a potential male sexual enhancement molecule via its high binding affinity for most erectile dysfunction-targeted proteins. They may require further toxicity and therapeutic evaluations in vivo.

Clinical benefits of vortioxetine 20 mg/day in patients with major depressive disorder.

BACKGROUND: Vortioxetine has demonstrated dose-dependent efficacy in patients with major depressive disorder (MDD), with the greatest effect observed with vortioxetine 20 mg/day. This analysis further explored the clinical relevance of the more rapid and greater improvement in depressive symptoms observed with vortioxetine 20 mg/day vs 10 mg/day. METHODS: Analysis of pooled data from six short-term (8-week), randomized, placebo-controlled, fixed-dose studies of vortioxetine 20 mg/day in patients with MDD (N = 2620). Symptomatic response (≥50% decrease in Montgomery-Åsberg Depression Rating Scale [MADRS] total score), sustained symptomatic response, and remission (MADRS total score ≤10) were assessed by vortioxetine dosage (20 or 10 mg/day). RESULTS: After 8 weeks, 51.4% of patients receiving vortioxetine 20 mg/day had achieved symptomatic response vs 46.0% of those receiving vortioxetine 10 mg/day (P < .05). Significantly more patients achieved symptomatic response vs placebo from week 2 onwards for vortioxetine 20 mg/day and from week 6 onwards for vortioxetine 10 mg/day (both P ≤ .05). Sustained response was achieved from week 4 for 26.0% of patients receiving vortioxetine 20 mg/day vs 19.1% of those receiving vortioxetine 10 mg/day (P < .01), increasing to 36.0% and 29.8%, respectively, over the 8-week treatment period (P < .05). At week 8, 32.0% of patients receiving vortioxetine 20 mg/day were in remission vs 28.2% of those receiving vortioxetine 10 mg/day (P = .09). Rates of adverse events and treatment withdrawal were not increased during the week following vortioxetine dose up-titration to 20 mg/day. CONCLUSION: Vortioxetine 20 mg/day provides more rapid and more sustained symptomatic response than vortioxetine 10 mg/day in patients with MDD, without compromising tolerability.

Exposure-Response Analyses of Olaparib in Real-Life Patients with Ovarian Cancer.

BACKGROUND: Olaparib is given in a fixed dose of twice-daily 300 mg in patients who are diagnosed with ovarian cancer, breast cancer, prostate cancer or pancreas cancer and has a high interpatient variability in pharmacokinetic exposure. The objective of this study was to investigate whether pharmacokinetic exposure of olaparib is related to efficacy and safety in a real-life patient' cohort. METHODS: A longitudinal observational study was conducted in patients who received olaparib for metastatic ovarian cancer of whom pharmacokinetic samples were collected. A Kaplan-Meier analyses was used to explore the relationship between olaparib exposure, measured as (calculated) minimum plasma concentrations (Cmin), and efficacy, Univariate and multivariate cox-regression analyses were performed. Also, the Cmin of patients who experienced toxicity was compared with patients who did not experience any toxicity. RESULTS: Thirty-five patients were included in the exposure-efficacy analyses, with a median olaparib Cmin of 1514 ng/mL. There was no statistical significant difference in PFS of patients below and above the median Cmin concentration of olaparib, with a hazard ratio of 1.06 (95% confidence interval: 0.46-2.45, p = 0.9)). For seven patients pharmacokinetic samples were available before toxicity occurred, these patients had a higher Cmin of olaparib in comparison with patients who had not experienced any toxicity (n = 33), but it was not statistically significant (p = 0.069). CONCLUSIONS: Our study shows that exposure of olaparib is not related to PFS. This suggests that the approved dose of olaparib yields sufficient target inhibition in the majority of patients.

The safety and efficacy of sequential intramuscular/oral ziprasidone treatment of acute episode in patients with schizophrenia: a multicenter, open-labeled study.

BACKGROUND: Ziprasidone mesylate injection is an atypical antipsychotic drug which is recently approved in China. In combination with its oral formulation, sequential therapy with ziprasidone brings new interventions to patients with agitation in the acute phase of schizophrenia. The purpose of this 7-day multicenter study conducted in China was to evaluate the efficacy and safety of ziprasidone sequential treatment through intramuscular/oral routes in agitated patients with schizophrenia. METHODS: A total of 95 patients were enrolled from three centers in this study. The study duration was 7 days. In the first 3 days, subjects were administered an intramuscular injection of ziprasidone 10-40 mg daily and started sequentially with oral ziprasidone 40-80 mg at dinner (or lunch) from the day of the last intramuscular injection. In the following 4 days, according to the severity of the symptoms and the drug response, 120-160 mg of ziprasidone was orally administered daily. In total, six visits were scheduled to assess the Positive and Negative Syndrome Scale (PANSS), the Behavioral Activity Rating Scale (BARS), the Clinical Global Impression of Severity (CGI-S), and Improvement (CGI-I) scores throughout the procedure. Lastly, adverse events were recorded during treatment. RESULTS: Out of the 95 patients that were enrolled, 83 cases were effectively completed. Visits 3, 4, 6, PANSS, and PANSS-excited component (PANSS-EC) subscale points, and Visit 2-Visit 6 viewpoints, BARS scale points, and baseline scores denote a progressive downward trend (P < 0.001). In this study, 62 adverse events were reported. The most common adverse events were extrapyramidal symptoms (EPS) (23 cases) and excessive sedation(10 cases), and 13 cases of prolonged QTc interval were reported. CONCLUSIONS: Ziprasidone IM demonstrated significant and rapid reduction in agitation, and sequential oral formulation keep stability and continuation of the treatment can further ensure efficacy. Ziprasidone sequential therapy may provide a new approach to acute agitation in schizophrenic patients. TRIAL REGISTRATION: The Chinese Clinical Trials Registry; URL: https://www.chictr.org.cn : ChiCTR-OIC-16007970.