Safety and effectiveness of lurasidone in the treatment of Chinese schizophrenia patients: An interim analysis of post-marketing surveillance.

BACKGROUND: Schizophrenia is a psychiatric disorder characterized by chronic or recurrent symptoms. Lurasidone was licensed in China in 2019 for the treatment of adult schizophrenia in adults with a maximum dose of 80 mg/d. However, post-market surveillance (PMS) with an adequate sample size is required for further validation of the drug's safety profile and effectiveness. AIM: To conduct PMS in real-world clinical settings and evaluate the safety and effectiveness of lurasidone in the Chinese population. METHODS: A prospective, multicenter, open-label, 12-wk surveillance was conducted in mainland China. All patients with schizophrenia from 10 sites who had begun medication with lurasidone between September 2019 and August 2022 were eligible for enrollment. Safety assessments included adverse events (AEs), adverse drug reactions (ADRs), extrapyramidal symptoms (EPS), akathisia, use of EPS drugs, weight gain, and laboratory values as metabolic parameters and the QTc interval. The effectiveness was assessed using the brief psychiatric rating scale (BPRS) from baseline to the end of treatment. RESULTS: A total of 965 patients were enrolled in the full analysis set and 894 in the safety set in this interim analysis. The average daily dose was 61.7 ± 19.08 mg (mean ± SD) during the treatment. AEs and ADRs were experienced by 101 patients (11.3%) and 78 patients (8.7%), respectively, which were mostly mild. EPS occurred in 25 individuals with a 2.8% incidence, including akathisia in 20 individuals (2.2%). Moreover, 59 patients received drugs for treating EPS during the treatment, with an incidence of 6.6% which dropped to 5.4% at the end of the treatment. The average weight change was 0.20 ± 2.36 kg (P = 0.01687) with 0.8% of patients showing a weight gain of ≥ 7% at week 12 compared with that at the baseline. The mean values of metabolic parameters and the QTc interval at baseline and week 12 were within normal ranges. The mean changes in total BPRS scores were -8.9 ± 9.76 (n = 959), -13.5 ± 12.29 (n = 959), and -16.8 ± 13.97 (n = 959) after 2/4, 6/8, and 12 wk, respectively (P < 0.001 for each visit compared with the baseline) using the last-observation-carried-forward method. CONCLUSION: The interim analysis of the PMS of adult patients with schizophrenia demonstrate the safety and effectiveness of lurasidone in the Chinese population. No new safety or efficacy concerns were identified.

[Clinical anatomical study on the treatment of carpal tunnel syndrome with classic Acupotomy].

OBJECTIVE: To explore the safety of classic Acupotomy in the treatment of carpal tunnel syndrome. METHODS: Twenty six adult specimens (15 males and 11 females), aged 60 to 95(82.54±6.94) years old, were selected from 10% formalin antiseptic fixation. There were 52 sides(two of them could not be tested). The study period was from November 2017 to May 2018. The specimens were collected from the body donation center of the school of basic medicine, Peking University. The operation of releasing the transverse carpal ligament on the human body specimen was simulated by the classic acupotomy, and the distance from the four points to the surrounding anatomical structure was measured to calculate the direct injury rate to the nerve and blood vessels, and the shortest distance between the acupotomy and the nerve and blood vessels was defined as ≥2 mm as safety. RESULTS: In the experimental operation, the direct injury rate of nerve and blood vessel was 14% and 12% respectively. There was significant difference in the rate of direct nerve injury between the four injection points (P<0.05). There was no significant difference in the rate of direct vascular injury between the four injection points (P>0.05). Among the four points, there was a statistically significant difference in the safety of nerves(P<0.05), and the safety of point 1 and point 3 of radial injection was higher than that of point 2 and point 4 of ulnar injection(P<0.05). There was significant difference in the safety of blood vessels between the four points(P<0.05), and the safety of radial point 1 was higher than that of ulnar point 2 and point 4 (P<0.05). CONCLUSION: The safety of the classic Acupotomy for carpal tunnel syndrome is related to the location of the needle entry point, and the safety of theradial proximal end of the needle is the highest.

Risk factors of hyperprolactinemia induced by risperidone and olanzapine and their correlations with plasma glucose and lipids.

BACKGROUND: Hyperprolactinemia is a common adverse reaction in patients with schizophrenia who take antipsychotic drugs; it often leads to treatment non-compliance in patients and has an adverse effect on their prognosis. AIMS: This study aimed to explore the risk factors of elevated prolactin (PRL) caused by risperidone (RIS) and olanzapine (OLZ) and the relationship between PRL and fasting plasma glucose and lipids. METHODS: Patients with schizophrenia were divided into two groups: 264 patients who were taking RIS and 175 patients who were taking OLZ. These two groups were further divided according to serum PRL levels: an elevated PRL group (>30 ng/mL) and a normal PRL group (PRL ≤30 ng/mL). The demographics, medication dosage, fasting plasma glucose, total cholesterol and triglycerides were compared in the two groups. Logistic regression analysis was performed to explore the risk factors of elevated PRL levels. RESULTS: Compared with the OLZ group, the RIS group had a greater number of patients with elevated PRL (155/264 vs 58/175). Either the RIS or the OLZ group, the proportion of elevated PRL was greater in female patients (RIS: χ2=6.76, p=0.009; OLZ: χ2=12.98, p<0.001) and with higher doses of the related drugs (RIS: U=-3.73, p<0.001; OLZ: U=-2.31, p=0.021). In patients taking RIS, the elevated PRL subgroup took the drug for a longer period (U=-2.76, p=0.006) and had lower triglyceride levels (U=2.76, p=0.006). In patients taking OLZ, the elevated PRL subgroup had lower fasting plasma glucose levels (U=2.29, p=0.022). Logistic regression analysis showed that gender, dose and fasting glucose levels were significantly associated with elevated PRL levels (RIS: p=0.001, OLZ: p<0.001; RIS: p<0.001; OLZ: p=0.003; RIS: p=0.020, OLZ: p=0.001, respectively). CONCLUSION: Compared with OLZ, RIS had a greater effect on PRL in patients with schizophrenia, and in patients with schizophrenia taking RIS or OLZ, gender and dose were significantly correlated with the PRL value. Moreover, the plasma glucose level of the group with elevated PRL was lower than that of the group with normal PRL. The results also showed that high serum PRL may be associated with a favourable glucose metabolic profile in patients with schizophrenia taking RIS or OLZ. Further studies are warranted to confirm this association. TRIAL REGISTRATION NUMBER: NCT02640911.

Quantitative efficacy of three antipsychotic drugs for schizophrenia based on a real-world study in China.

Atypical antipsychotics exert remarkable long-term efficacy on the personal and social functions of schizophrenic patients. However, quantitative information on the social function of schizophrenic patients treated with atypical antipsychotics is scarce in the current clinical guidelines. In this study, we established pharmacodynamic models to quantify the time-efficacy relationship of three antipsychotic drugs based on the data from a real-world study conducted in China. A total of 373 schizophrenic patients who received antipsychotic monotherapy with olanzapine (n = 144), risperidone (n = 160), or aripiprazole (n = 69) were selected from a three-year prospective, multicenter study. The follow-up times were 13, 26, 52, 78, 104, 130, and 156 weeks after baseline. A time-efficacy model was developed with nonlinear mixed effect method based on changes in Personal and Social Performance (PSP) score compared with the baseline level. Crucial pharmacodynamic parameters, including maximum efficacy and drug onset time, were used to distinguish the efficacy of the three drugs. We quantified the time course of PSP improvement in patients after treatment with these three antipsychotics: olanzapine, risperidone, and aripiprazole reached an Emax value of 80.3%, 68.2%, and 23.9% at weeks 56.7, 29.2, and 36.8, respectively. General psychotic symptoms, onset frequency, and illness course were identified as significant factors affecting the efficacy of these drugs. The newly constructed models provide an evidence of the benefit of long-term maintenance therapy with atypical antipsychotics in individualized schizophrenia treatment in China.

[Research progress of stenosing tenosynovitis of radial styloid process based on anatomical structure].

Stenosing tenosynovitis of styloid process of radius(de Quervain's disease) which abductor pollicis longus and extensor pollicis brevis in the first extensor chamber are affected by resistance when sliding, the incidence is affected by anatomical variations. Symptoms, signs and auxiliary examinations can diagnose the disease. Slight dQS can be improved by rest, brace, restriction activities, and oral medications. Chinese medicine and physiotherapy also reduce the disease. Needle knife therapy is a Traditional Chinese medicine minimally invasive surgery, which is also a step-by-step treatment between conservative treatment and open surgery to loosening the compression of the first extensor chamber. Steroid injection is a more common treatment in this disease, and its efficacy is related to the accuracy of the injection and is affected by the severity of the patient's anatomical variation. Identifying the spacing within the first extensor chamber under ultrasound can help patients better choose conservative or surgical treatment. Surgical treatment can more completely change the condition of dQD from anatomical structure, and clinical should pay attention to the choice of surgical procedure to improve the efficacy and reduce the occurrence of surgical complications. This article discusses the pathogenesis, diagnosis and treatment of the disease from the perspective of anatomical structure. It mainly analyzes the therapeutic targets and the clinical application, which aims to provide reference for the diagnosis and treatment of de Quervain disease.

[Clinical manifestations and imaging analysis of cervicogenic headache].

OBJECTIVE: To investigate the clinical characteristics and mechanism of cervicogenic headache. METHODS: Fifty-seven patients with cervicogenic headache who were treated from May 2013 to December 2017 and had complete imaging data were selected, including 18 males and 39 females with an average age of(43.26±10.39) years old ranging from 20 to 63 years old. The duration of the disease was 4 months to 35 years with a mean of (11.74±9.47) years. The pain situation, iconography and Tinel sign were analyzed. RESULTS: The patients with cervicogenic headache often had bilateral pain. The regions mainly concentrated in the temporal region, with occipital, head or orbit pains. The VAS scores decreased with the duration of the disease. There were many cases of disc herniation(91.30%), vertebral instability(73.91%), atlantoaxial displacement(56.52%), curvature change of cervicogenic vertebra(54.35%). The number of positive Tinel sign points was between 3 and 24 (13.58±5.8) per patient. The number and extent of Tinel sign were significantly different between the affected side and healthy side(P<0.05). C2,3 facet joints(92.98%), post mastoid(89.47%), occipital concavity(89.47%), C3,4 facet joints(84.21%), third occipital nerve(80.70%) were the positive Tinel sign points in patients with cervicogenic headache. CONCLUSIONS: The iconography changes of cervicogenic headache and Tinel sign may contribute to the clinical diagnosis and mechanism of the disease.

Efficacy and Safety of Agomelatine vs Paroxetine Hydrochloride in Chinese Han Patients with Major Depressive Disorder: A Multicentre, Double-Blind, Noninferiority, Randomized Controlled Trial.

PURPOSE: The purpose of this study is to investigate the efficacy, safety, and tolerability of agomelatine and paroxetine in Chinese Han patients with major depressive disorder (MDD). METHODS: A 8-week, double-blind, randomized, parallel study was conducted in 14 medical centers in mainland China from December 2011 to September 2012. A total of 264 subjects with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD were randomly assigned to receive agomelatine 25-50 mg/d (n = 132) or paroxetine 20-40 mg/d (n = 132). The primary efficacy was evaluated by the decrease of Hamilton Depression Rating Scale (HAM-D17) scores. The secondary measurements of efficacy included Hamilton Anxiety Rating Scale, Montgomery-Asberg Depression Rating Scale, Sheehan Disability Scale, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement. The laboratory test abnormity, and observed and self-reported adverse events were all assessed as the measurements of safety and tolerability. RESULTS: Both the agomelatine and paroxetine groups showed significant improvement from baseline to the end point (P < 0.05) without between-group differences (P > 0.05). The mean decrease of HAM-D17 of agomelatine group was not inferior to the paroxetine group over the 8-week treatment (agomelatine 15.26 ± 6.44 vs paroxetine 14.87 ± 5.89, δ = 2.0; µA-µB 95% confidence interval, -1.13 to 1.91). The percentage of responders at the last postbaseline assessment was similar in the 2 groups on both HAM-D17 (agomelatine 66.15% vs paroxetine 63.49%) and Clinical Global Impressions-Improvement (agomelatine 79.09% vs paroxetine 80.36%). The anxiety (Hamilton Anxiety Rating Scale) and sleep symptoms (sleep items of HAM-D17) of the patients were improved significantly in the 2 groups at week 8 without between-group differences (P > 0.05). The incidence of overall adverse events was similar in the 2 groups (agomelatine 49.62% vs paroxetine 56.15%, P > 0.05). The incidence of adverse events in skin and subcutaneous tissue was higher in the paroxetine group than in the agomelatine group (none in agomelatine and 4.62% in paroxetine, P = 0.0144). CONCLUSIONS: Agomelatine showed equivalent antidepressant efficacy to paroxetine in treating MDD patients after 8 weeks of treatment with an acceptable safety.

Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients.

AIM: Extrapyramidal syndrome (EPS) is most commonly affected by typical antipsychotic drugs that have a high affinity with the D2 receptor. Recently, many research groups have reported on the positive relationship between the genetic variations in the DRD2 gene and the therapeutic response in schizophrenia patients as a result of the role of variations in the receptor in modulating receptor expression. In this study, we evaluate the role DRD2 plays in chlorpromazine-induced EPS in schizophrenic patients. METHODS: We identified seven SNP(single nucleotide polymorphism) (-141Cins>del, TaqIB, TaqID, Ser311Cys, rs6275, rs6277 and TaqIA) in the DRD2 gene in 146 schizophrenic inpatients (59 with EPS and 87 without EPS according to the Simpson-Angus Scale) treated with chlorpromazine after 8 weeks. The alleles of all loci were determined by PCR (polymerase chain reaction). RESULTS: Polymorphisms TaqID, Ser311Cys and rs6277 were not polymorphic in the population recruited in the present study. No statistical significance was found in the allele distribution of -141Cins>del, TaqIB, rs6275 and TaqIA or in the estimated haplotypes (constituted by TaqIB, rs6275 and TaqIA) in linkage disequilibrium between the two groups. CONCLUSION: Our results did not lend strong support to the view that the genetic variation of the DRD2 gene plays a major role in the individually variable adverse effect induced by chlorpromazine, at least in Chinese patients with schizophrenia. Our results confirmed a previous study on the relationship between DRD2 and EPS in Caucasians.