Effectiveness and Safety of Flupentixol and Melitracen Tablets for the Treatment of Patients with Persistent Idiopathic Facial Pain: A Retrospective Observational Study.

BACKGROUND: Flupentixol and melitracen are being investigated for their potential effectiveness in managing persistent idiopathic facial pain (PIFP), based on their mechanisms of action as dopamine receptor antagonists and noradrenaline/serotonin reuptake inhibitors, respectively. The efficacy and safety of flupentixol and melitracen (FM) tablets in treating PIFP were retrospectively analyzed at our hospital. OBJECTIVES: The aim of this study is to determine the effectiveness and safety of FM tablets in treating PIFP. STUDY DESIGN: Retrospective unicentric cohort design. SETTING: An academic university hospital. METHODS: A retrospective analysis was conducted on a cohort comprising 128 patients with a definite diagnoses of PIFP who were treated with FM tablets (flupentixol 0.5 mg and melitracen 10 mg tablet, >= 4 tablets/d) from January 2022 through May 2023 at an academic university hospital. Baseline conditions were statistically described, and Numeric Rating Scale (NRS-11) scores of pain levels before and during treatment were collected. Pain relief rates were calculated. Differences in baseline characteristics between responsive and unresponsive patients were evaluated using statistical tests. Additionally, the side effects experienced during treatment were summarized. RESULTS: Among the included 128 patients, 105 (82.0%) patients achieved pain relief (pain NRS-11 score reduction rate >= 50%). The median treatment onset time was 3 (1-7) days. NRS-11 scores of responsive patients at week 2, week 4, week 8, and week 12 were significantly lower than the baseline NRS-11 scores (P < 0.001), regardless of their Hamilton Depression Rating Scale score. Pain duration was the only factor that related to responsiveness (Wilcoxon rank sum test, P < 0.001; logistic regression, P = 0.001). No serious side effects that could affect patients' lives were observed during the first week of treatments. LIMITATIONS: Due to its retrospective nature, this study is limited by its lack of a randomized control. The lack of data on nonresponders who did not achieve significant pain relief hinders assessing overall change and the placebo effects'. Patients previously treated with antidepressants were excluded, making it hard to determine if FM tablets were a better treatment for PIFP. Additionally, the small sample size in a single center may be influenced by chance variation in pain relief. CONCLUSIONS: FM tablets showed its potential in the management of PIFP with considerable efficacy and safety. Early administration of FM tablets after a PIFP diagnosis may result in a high possibility of pain relief.

There is more to this fever than meets the eye: A case of neuroleptic malignant-like syndrome (NMLS) secondary to withdrawal of procyclidine and L-dopa on a background of long-standing flupenthixol depot use.

This case report highlights the risk of development of Neuroleptic Malignant-Like Syndrome secondary to withdrawal of procyclidine with brief withdrawal of L-dopa and long-term typical antipsychotic depot. The patient responded to reintroduction of procyclidine, sedation and supportive treatment. The mechanism and management of NMS and NMLS is also reviewed. This case emphasises that any changes in antipsychotic and antiparkinsonian medications should be undertaken with extreme caution and patient should be closely monitored for development of NMLS after alteration in these medications.

The management challenges of a case with Flupentixol-induced neuroleptic malignant syndrome.

BACKGROUND: Neuroleptic malignant syndrome (NMS) is a rare and life-threatening reaction. The incidence rate of NMS has dropped because of the higher use of atypical antipsychotics, compared with the typical ones. The mortality rate in patients taking injectable antipsychotics has been also by 38%. AIM: Here, a case developing the NMS symptoms following Flupentixol (FPX) use was reported. CASE PRESENTATION: The patient was a 46-year-old man with the history of schizoaffective disorder (SAD) and recently on six-weekly doses of long-acting (LA) typical antipsychotic drugs. He was referred with a fever, sweating, a food intolerance, mutism, and disorientation in 2019. He was presented with generalized rigidity, negativism, and neck stiffness. The patient's initial creatine phosphokinase (CPK) level was 1476 IU/L, which gradually elevated to 3997 IU/L on Day 26. NMS was further diagnosed, in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, and the score 9+ in the Naranjo Algorithm as the adverse drug reaction probability scale. Afterward, the patient was treated with bromocriptine at a dose of 5 mg 3 times a day, which progressively reached a maximum of 50 mg. He experienced sepsis and resistant respiratory infection several times. The case was finally discharged after 66 days of hospitalization, with a high level of consciousness, but limited verbal communication, in a fever-free condition with the oral administration of bromocriptine and lorazepam. CONCLUSION: In conclusion, there were suggestions for the management challenges of NMS in patients receiving LA injectable antipsychotic agents.

Analysis of the use of antidepressants in patients from non-psychiatric departments in general hospital.

This study aimed to analyze the use of antidepressants in non-psychiatric departments. The data of patients treated with antidepressants in non-psychiatric departments of the First Affiliated Hospital of Xi 'an Jiaotong University, were collected from 2014 to 2018. The average annual growth rate of antidepressants use was 22.83%. According to the number of patients at discharge, the classification descending order was: SSRIs, Flupenthixol-TCA, SNRIs, TCAs, SARIs, and NaSSA. Sertraline and flupenthixol-melitracen were the main drugs used in SSRIs and Flupenthixol-TCA, respectively. Neurology, Cardiology, and Geriatrics were the main departments prescribing SSRIs, Flupenthixol-TCA and SNRIs. The antidepressants used by all patients were mainly SSRIs according to drug classification, but the specific drug use in unclear diagnosis group was dominated by flupenthixol-melitracen, while it was sertraline in clear diagnosis group. The proportion of Flupenthixol-TCA in anxiety state group was higher than that in depression state group, While the situation in SSRIs is the opposite. More guidelines should be formulated to improve the recognition of comorbidities between specialized diseases and psychiatric disorders. Also, multi-level training should be implemented to perform the standard diagnosis and medication of mental disorders in clinical practice.

The combination therapy with esomeprazole and flupenthixol/melitracen in symptom improvement of erosive gastritis complicated with negative feelings compared with Esomeprazole alone.

The purpose of this study was to evaluate the co-prescription efficacy of esomeprazole and flupenthixol/melitracen relative to that of solitary esomeprazole on erosive gastritis complicated with negative feelings. 140 erosive gastritis patients complicated with negative feelings enrolled in the present study. Seventy cases in the control group took esomeprazole, and 70 cases in the observation group received esomeprazole plus flupenthixol/Melitracen, both for 4 weeks. We gastroscopically checked the clinical symptoms, mucosal erosion, PGE2 and MDA levels in gastric mucosa, anxiety, depression, and recurrence before and after treatment in the groups. After treatment, the observation group had lower scores of clinical symptoms, mucosal erosions, Hamilton Depression Rating Scale (HAMD), and Hamilton Depression Rating Scale (HAMA) than the control group (p<0.05); as well, the observation group showed higher PGE2 and lower MDA levels than the control group (p<0.05); during six months of follow-up (100% follow-up rate), 16 and 34 recurrent cases occurred, respectively, in the observation and control groups (p<0.05).  Co-prescription of esomeprazole and flupenthixol/melitracen improved the clinical symptoms and mucosal erosions, relieved negative feelings and reduced the recurrence rate. The efficacy of the co-prescription is higher than that of the solitary prescription.

[A preliminary study of resting-state fMRI in patients with diarrhea-type irritable bowel syndrome after pinaverium bromide combined treatment with flupentixol-melitracen].

Objective: To observe the difference of brain activity in patients with diarrhea-type irritable bowel syndrome (IBS-D) treated with pinaverium bromide (PB) combined with flupentixol-melitracen (FM), and to explore the mechanism of efficacy of combined with anxiolytic/antidepressant drugs in IBS-D patients at the central level, using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Forty-eight patients with IBS-D, including 28 males, 20 females, mean age 22-48 (33±7) years, were selected from the Affiliated Hospital of Hangzhou Normal University from October 2015 to October 2018.All patients with IBS-D underwent rs-fMRI scans before and after receiving either PB (basic treatment group, n=16), PB combined with FM (combination therapy group, n=16), or no medication (no treatment group, n=16). Rs-fMRI regional homogeneity (ReHo) parameter among the three groups of patients were compared using One-way ANOVA analysis and post analysis.Partial correlation and mediation analyses were performed on ReHo values and the improvement of symptoms scores (gastrointestinal symptom rating scale(GSRS) and hospital anxiety/depression scale (HAD)) in the two medicated groups. Results: No significant differences in ReHo values were observed among the three groups before treatment. Compared with patients on no-medication, patients receiving either PB or PB-FM showed decreased ReHo in the striatum, insular lobe, medial prefrontal cortex (MPFC) and subcallosal gyrus, and increased ReHo in the occipital cortex. In particular, the combined treatment group showed more extensive decreased ReHo in the left thalamus and left temporal pole, and increased in the left precuneus. Compared with the basic treatment group, the combined treatment group showed decreased ReHo in the right putamen, right insula, right MPFC and subcallosal gyrus, and increased ReHo in the left precuneus. In addition, the combined treatment group demonstrated a positive correlation between ReHo values in the left thalamus and the improvement of HAD score (r=0.653, P=0.011) , and a negative correlation between ReHo values in left precuneus and the improvement of GSRS and HAD score (r=-0.771, P=0.001; r=-0.716, P=0.004). ReHo values in the left precuneus were observed to mediate between gastrointestinal symptoms and anxiety-depressive symptoms in the combined treatment group. Conclusions: The efficacy of PB combined with FM is superior to PB alone in the treatment of IBS. In addition to more extensive changes in pain-related brain areas, IBS-D patients treated with anxiolytic/antidepressant also show changes in default network and brain areas related to emotional regulation, and are associated with improvement in gastrointestinal symptoms, anxiety and depression.

Benefit of small dose antidepressants for functional dyspepsia: Experience from a tertiary center in eastern China.

BACKGROUND: Traditional treatment of functional dyspepsia (FD) is unsatisfactory in a subgroup of patients with FD, and the potential role of antidepressant medications also has not been definitely clarified. To provide more evidence for future optimal practice recommendations, we reviewed a 1-year clinical database of antidepressant agents applied in outpatients with FD. METHODS: Clinical presentations, treatment course, and outcomes were determined by chart review of patients referring to the functional gastrointestinal disorders specialist clinic. One hundred thirty patients with FD were included for further analysis. RESULTS: Patients were treated with different antidepressant drugs according to individual symptoms. The most commonly used drugs were flupenthixol melitracen and fluoxetine. Improvement and complete remission occurred in 93.8% and 54.6% of patients, respectively. There was a trend toward superior outcome for citalopram compared to sulpiride and mirtazapine in overall analysis. Meanwhile, regimens containing fluoxetine had significant increased remission rate compared to any other antidepressant regimens in postprandial distress syndrome subgroup analysis. Furthermore, older patients were more likely to achieve remission. However, sex and symptom duration were not associated with symptom remission. Finally, 11.5% of patients experienced adverse events. CONCLUSIONS: This retrospective cohort study indicated that small dose antidepressant therapy, especially citalopram and fluoxetine, is an effective and well tolerated treatment option for refractory FD.

Prolactin, flupenthixol decanoate and first episode schizophrenia - clinical and laboratory correlates.

First-episode psychosis (FEP) patients are more sensitive to neuroleptic side-effects such as hyperprolactinemia. We examined the prolactin levels of previously minimally treated patients with first episode schizophrenia over their first year of treatment with flupenthixol decanoate and the relationship between prolactin levels, gender and clinical features of schizophrenia. Prolactin levels were assessed at three monthly intervals in 126 patients with first-episode schizophrenia in a single-site study conducted over 12 months during treatment with flupenthixol decanoate according to a fixed protocol. The mean prolactin level for the total sample was 11.91 ng/ml (standard deviation [SD]15.52) at baseline. Women had higher levels of prolactin than men at month 3, 6 and 12, reaching statistical significance at month 12 (p = 0.02). At 12 months more women than men had hyperprolactinemia (defined as more than 20 ng/ml for males, and as more than 25 ng/ml for females (p = 0.007). Using a mixed effect model, there was a significant association between prolactin change scores over 12 months and gender (p = 0.025) as well as Positive and Negative Syndrome Scale (PANSS) total scores (p = 0.001). In addition female gender (p = 0.04) and age (p = 0.02) correlated with the risk of hyperprolactinemia as categorical variable. In this study treatment with flupenthixol decanoate was associated with relatively low levels of hyperprolactinemia, likely owing to flupenthixol's relatively atypical mode of action, as well as to the low doses used in our study. We found an inverse correlation between total PANSS scores and prolactin levels, which could support the suggested theory of prolactin having antipsychotic properties. Our study confirms the importance of gender on the prolactin raising effects of antipsychotic treatment.

Electroconvulsive therapy for treatment-resistant schizophrenia.

BACKGROUND: Electroconvulsive therapy (ECT) involves the induction of a seizure by the administration of an electrical stimulus via electrodes usually placed bilaterally on the scalp and was introduced as a treatment for schizophrenia in 1938. However, ECT is a controversial treatment with concerns about long-term side effects such a memory loss. Therefore, it is important to determine its clinical efficacy and safety for people with schizophrenia who are not responding to their treatment. OBJECTIVES: Our primary objective was to assess the effects (benefits and harms) of ECT for people with treatment-resistant schizophrenia.Our secondary objectives were to determine whether ECT produces a differential response in people: who are treated with unilateral compared to bilateral ECT; who have had a long (more than 12 sessions) or a short course of ECT; who are given continuation or maintenance ECT; who are diagnosed with well-defined treatment-resistant schizophrenia as opposed to less rigorously defined treatment-resistant schizophrenia (who would be expected to have a greater affective component to their illness). SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including clinical trial registries on 9 September 2015 and 4 August 2017. There were no limitations on language, date, document type, or publication status for the inclusion of records in the register. We also inspected references of all the included records to identify further relevant studies. SELECTION CRITERIA: Randomised controlled trials investigating the effects of ECT in people with treatment-resistant schizophrenia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. For binary outcomes, we calculated the risk ratio (RR) and its 95% confidence intervals (CIs), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between the groups and its 95% CIs. We employed the fixed-effect model for all analyses. We assessed risk of bias for the included studies and created 'Summary of findings' tables using the GRADE framework. MAIN RESULTS: We included 15 studies involving 1285 participants (1264 completers with an average age of 18 to 46 years) with treatment-resistant schizophrenia. We rated most studies (14/15, 93.3%) as at high risk of bias due to issues related to the blinding of participants and personnel. Our main outcomes of interest were: (i) clinically important response to treatment; (ii) clinically important change in cognitive functioning; (iii) leaving the study early; (iv) clinically important change in general mental state; (v) clinically important change in general functioning; (vi) number hospitalised; and (vii) death. No trial reported data on death.The included trials reported useable data for four comparisons: ECT plus standard care compared with sham-ECT added to standard care; ECT plus standard care compared with antipsychotic added to standard care; ECT plus standard care compared with standard care; and ECT alone compared with antipsychotic alone.For the comparison ECT plus standard care versus sham-ECT plus standard care, only average endpoint BPRS (Brief Psychiatric Rating Scale) scores from one study were available for mental state; no clear difference between groups was observed (short term; MD 3.60, 95% CI -3.69 to 10.89; participants = 25; studies = 1; very low-quality evidence). One study reported data for service use, measured as number readmitted; there was a clear difference favouring the ECT group (short term; RR 0.29, 95% CI 0.10 to 0.85; participants = 25; studies = 1; low-quality evidence).When ECT plus standard care was compared with antipsychotics (clozapine) plus standard care, data from one study showed no clear difference for clinically important response to treatment (medium term; RR 1.23, 95% CI 0.95 to 1.58; participants = 162; studies = 1; low-quality evidence). Clinically important change in mental state data were not available, but average endpoint BPRS scores were reported. A positive effect for the ECT group was found (short-term BPRS; MD -5.20, 95% CI -7.93 to -2.47; participants = 162; studies = 1; very low-quality evidence).When ECT plus standard care was compared with standard care, more participants in the ECT group had a clinically important response (medium term; RR 2.06, 95% CI 1.75 to 2.42; participants = 819; studies = 9; moderate-quality evidence). Data on clinically important change in cognitive functioning were not available, but data for memory deterioration were reported. Results showed that adding ECT to standard care may increase the risk of memory deterioration (short term; RR 27.00, 95% CI 1.67 to 437.68; participants = 72; studies = 1; very low-quality evidence). There were no clear differences between groups in satisfaction and acceptability of treatment, measured as leaving the study early (medium term; RR 1.18, 95% CI 0.38 to 3.63; participants = 354; studies = 3; very low-quality evidence). Only average endpoint scale scores were available for mental state (BPRS) and general functioning (Global Assessment of Functioning). There were clear differences in scores, favouring ECT group for mental state (medium term; MD -11.18, 95% CI -12.61 to -9.76; participants = 345; studies = 2; low-quality evidence) and general functioning (medium term; MD 10.66, 95% CI 6.98 to 14.34; participants = 97; studies = 2; very low-quality evidence).For the comparison ECT alone versus antipsychotics (flupenthixol) alone, only average endpoint scale scores were available for mental state and general functioning. Mental state scores were similar between groups (medium-term BPRS; MD -0.93, 95% CI -6.95 to 5.09; participants = 30; studies = 1; very low-quality evidence); general functioning scores were also similar between groups (medium-term Global Assessment of Functioning; MD -0.66, 95% CI -3.60 to 2.28; participants = 30; studies = 1; very low-quality evidence). AUTHORS' CONCLUSIONS: Moderate-quality evidence indicates that relative to standard care, ECT has a positive effect on medium-term clinical response for people with treatment-resistant schizophrenia. However, there is no clear and convincing advantage or disadvantage for adding ECT to standard care for other outcomes. The available evidence was also too weak to indicate whether adding ECT to standard care is superior or inferior to adding sham-ECT or other antipsychotics to standard care, and there was insufficient evidence to support or refute the use of ECT alone. More good-quality evidence is needed before firm conclusions can be made.

Efficacy and safety of pinaverium bromide combined with flupentixol-melitracen for diarrhea-type irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND: There are many trials on the combination of Pinaverium bromide (PB) and Flupentixol-melitracen (FM) in the treatment of diarrhea-type irritable bowel syndrome (IBS-D), but the sample sizes are small, and the research conclusions are inconsistent. Thus, a meta-analysis was performed, aiming to evaluate the efficacy and safety of this combination therapy in patients with IBS-D. METHODS: A systematic literature search was conducted in 7 databases covering the period up to July 2018 to identify randomized controlled trials (RCTs) of PB combined with FM versus PB alone for IBS-D. The primary outcome was the total symptom relief rate. The other outcomes were the adverse events rate, HAMA/SAS score, and HAMD/SDS score. The methodological quality of the RCTs was assessed independently using 6 criteria according to the Cochrane Collaboration. All data were analyzed using Review Manager 5.3. RESULTS: Fifteen RCTs with 1487 participants were identified from 2005 to 2018. Compared with PB alone, 15 RCTs showed significant effects of PB plus FM in terms of improved symptom relief in patients with IBS-D (n = 1487, OR = 5.17, 95%CI, 3.79-7.07, P < .00001). Eleven RCTs reported adverse effects in both the PB plus FM and PB groups, there was no statistically significant difference in the adverse events rate between the 2 groups (n = 1207, OR = 2.91, 95%CI, 0.91-9.28, P = 0.07). Two RCTs and 3 RCTs reported HAMA and HAMD scores respectively, and 3 RCTs reported both SAS and SDS scores. After treatment, the above scores in the PB plus FM group were significantly lower than the PB group (all P < .01). However, the trials were deemed to have a medium risk of bias. CONCLUSIONS: The efficacy of PB combined with FM is superior to PB alone in the treatment of IBS-D, and it is safe for clinical use. However, the conclusions still need to be verified by conducting more large-scale and high-quality RCTs.

Changes in insight over the first 24 months of treatment in schizophrenia spectrum disorders.

BACKGROUND: While insight in schizophrenia improves with treatment, significant impairments often persist. The degree of persistence is not well characterised. AIMS: We assessed patient and clinician-rated changes in insight in acutely ill, minimally treated first-episode schizophrenia spectrum disorder patients over 24 months of standardised treatment with a depot antipsychotic. METHOD: This single arm open label longitudinal cohort study included 105 participants with first-episode schizophrenia, schizophreniform or schizoaffective disorder. Insight was assessed at months 0, 6, 12 and 24 using the patient-rated Birchwood Insight Scale (BIS) and clinician-rated global insight item of the Positive and Negative Syndrome Scale (PANSS). Changes in insight over time were assessed using linear mixed-effect models for continuous repeated measures. Relationships between insight and psychopathology, functionality, cognition and quality of life were assessed with regression models. RESULTS: There was significant improvement over time for the PANSS insight item (p < 0.0001). However, the only significant improvement for the BIS was with the Need for Treatment subscale (p = 0.01). There were no significant improvements noted for the Symptom Attribution (p = 0.7) and Illness Awareness (p = 0.2) subscales, as well as the BIS Total score (p = 0.6). Apart from depressive symptoms at baseline, there were no significant predictors of patient-rated insight. CONCLUSIONS: Clinicians should note that, even when treatment is assured and response is favourable, fundamental impairments in patient-rated insight persist.

[Observation of Flupentixol and melitracen on curative effect of sudden deafness patients with anxiety and depression in different stages].

Objective:To investigate the efficacy of flupentixol melitracen on different stages of sudden deafness patients with anxiety and depression.Method:Totally one hundred and sixty-three sudden deafness patients with anxiety and depression were randomly divided into two groups: experimental group(81 cases) and control group (82 cases). All patients were given routine treatment for 2 weeks. The experimental group was given oral flupentixol melitracen (1 tablet/day)for a period of 3 months. The hearing, tinnitus effect and vertigo treatment course were observed and compared. Curing rate of tinnitus at 2 weeks, 3 months and 6 months after treatment, self-rating anxiety scale (SAS) and depressive state scale (self-rating depression scale, SDS) score were collected and compared.Result:Total efficiency of hearing and tinnitus of experimental group(86.42%,84.21%)were higher than that of the control group(67.07%,61.29%);the vertigo cured the average treatment time of experimental group days was less than that of the control groupdays,all the differences were statistically significant.After treatment,the average hearing threshold value of the two groups of patients were lower than that before treatment,the low frequency descent type, high-frequency descent type,flat down type and total deafness type thresholds of the experimental group were lower than of the control group,all the differences were statistically significant.The tinnitus cure rate of experiment group were higher than the control group at 3months and 6 months after treatment,the differences were statistically significant;and after 3months and 6 months treatment tinnitus cure rate higher of the experimental group than that of after 2 weeks the treatment,the difference was statistically significant.After 2 weeks,3 months and 6 months treatment,the SAS and SDS scores of two groups were lower than that before treatment.The SAS and SDS scores of the experimental group decreased after 2 weeks,3 months and 6 months treatment, and the difference was statistically significant at different time points,the SAS,SDS scores of experimental group after treatment were lower than the control group at the same time,the differences were statistically significant.Conclusion:For the sudden deafness patients with anxiety and depression , the combination of flupentixol melitracen on the basis of conventional therapy can improve the clinical efficacy, the patient's mental status and long-term therapeutic effect of tinnitus..

Modification of the association between antipsychotic treatment response and childhood adversity by MMP9 gene variants in a first-episode schizophrenia cohort.

Antipsychotics remain the most effective, and wide used option for ameliorating the symptoms of schizophrenia. However, inter-individual differences in treatment outcome are vast and suggest a role for genetic and environmental factors in affording favourable outcomes. A notable epigenetic relationship which has gained considerable traction in recent literature is the way in which the severity of childhood trauma can modify associations seen between genetic variation and antipsychotic treatment response. A potential mechanism of action which may facilitate this relationship is synaptic plasticity. This study investigated the role of variants in matrix metallopeptidase 9 (MMP9), a gene involved in synaptic plasticity, with treatment outcome considering the severity of childhood trauma as an interacting variable. The cohort comprised South African first episode schizophrenia patients treated with a single injectable antipsychotic, flupenthixol decanoate, monitored over 12 months. Relationships between novel and previously described variants, and haplotypes, with antipsychotic treatment response were found to be modified when considering childhood trauma as an interacting variable. This study provides the first evidence for the involvement of polymorphisms within MMP9 and the severity of childhood trauma in antipsychotic treatment response, and warrants further investigation into the role gene-environment interactions may play in the betterment of antipsychotic treatment strategies.

[Effect analysis on Deanxit combined with Shuganjieyu capsule in the treatment of refractory gastroesophageal reflux disease].

Objective: To investigate the curative effect of Deanxit combined with Shuganjieyu capsule on the treatment of refractory gastroesophageal reflux disease. Methods: A total of 125 patients with refractory gastroesophageal reflux disease who had failed in standard lansolazole capsule treatment in the Department of Gastroenterology, First People's Hospital of Neijiang were selected. According to the symptom scores and mood scores of gastroesophageal reflux disease, patients were randomly and double-blindly divided into five groups. Group A(Lansoprazole Capsules + Mosapride Citrate + Deanxit), B(Lansoprazole Capsules + Mosapride Citrate + Shuganjieyu capsule), C(Lansoprazole Capsules + Mosapride Citrate+ Deanxit + Shuganjieyu capsule) and D(Deanxit) groups are study groups, the other was control group (Lansoprazole Capsules + Mosapride Citrate). The scores of symptoms and mood were compared after 4 weeks and 8 weeks of treatment. Results: The clinical symptoms score, HAMA and HAMD scores were significantly lower in the all study groups in comparison to the control group after 4 weeks and 8 weeks therapy. The clinical symptoms score, HAMA and HAMD scores in group C were significantly lower than those in group A and B (P<0.05), while the difference between group A and B was not statistically significant(P>0.05). The HAMA and HAMD scores of group D were significantly higher than those of group A, B, C and control group, and the differences were statistically significant (P<0.05). The total effective rate of study groups were significantly higher than those of the control group, and the difference was statistically significant (P<0.05). The total effective rate of group C was significantly higher than that of group A and B (χ(2)=6.47, P<0.05). The total effective rate of group A at the end of the 8th week was significantly higher than that of group B (χ(2)=6.52, P<0.05). The total effective rate of group D at the end of the 4th and 8th week was significantly lower than those of the group A, B, C and control group, the difference was statistically significant (χ(2)=5.85, P<0.05). Conclusions: Deanxit combined with Shuganjieyu capsule is significantly effective in treatment of refractory gastroesophageal reflux disease, which can effectively improve the total treatment efficiency, reduce the symptom scores and mood scores of gastroesophageal reflux disease patients.

Modulating cancer cell survival by targeting intracellular cholesterol transport.

BACKGROUND: Demand for cholesterol is high in certain cancers making them potentially sensitive to therapeutic strategies targeting cellular cholesterol homoeostasis. A potential approach involves disruption of intracellular cholesterol transport, which occurs in Niemann-Pick disease as a result of acid sphingomyelinase (ASM) deficiency. Hence, a class of lysosomotropic compounds that were identified as functional ASM inhibitors (FIASMAs) might exhibit chemotherapeutic activity by disrupting cancer cell cholesterol homoeostasis. METHODS: Here, the chemotherapeutic utility of ASM inhibition was investigated. The effect of FIASMAs on intracellular cholesterol levels, cholesterol homoeostasis, cellular endocytosis and signalling cascades were investigated. The in vivo efficacy of ASM inhibition was demonstrated using melanoma xenografts and a nanoparticle formulation was developed to overcome dose-limiting CNS-associated side effects of certain FIASMAs. RESULTS: Functional ASM inhibitors inhibited intracellular cholesterol transport leading to disruption of autophagic flux, cellular endocytosis and receptor tyrosine kinase signalling. Consequently, major oncogenic signalling cascades on which cancer cells were reliant for survival were inhibited. Two tested ASM inhibitors, perphenazine and fluphenazine that are also clinically used as antipsychotics, were effective in inhibiting xenografted tumour growth. Nanoliposomal encapsulation of the perphenazine enhanced its chemotherapeutic efficacy while decreasing CNS-associated side effects. CONCLUSIONS: This study suggests that disruption of intracellular cholesterol transport by targeting ASM could be utilised as a potential chemotherapeutic approach for treating cancer.

Fine-mapping of antipsychotic response genome-wide association studies reveals novel regulatory mechanisms.

AIM: Noncoding variation has demonstrated regulatory effects on disease treatment outcomes. This study investigated the potential functionality of previously implicated noncoding variants on schizophrenia treatment response. MATERIALS & METHODS: Predicted regulatory potential of variation identified from antipsychotic response genome-wide association studies was determined. Prioritized variants were assessed for association(s) with treatment outcomes in a South African first episode schizophrenia cohort (n = 103). RESULTS: Bioinformatic and association results implicated a relationship between regulatory variants, expression of MANBA, COL9A2 and NFKB1, and treatment response. Three SNPs were associated with poor outcomes (rs230493: p = 1.88 × 10-6; rs3774959: p = 1.75 × 10-5; and rs230504: p = 1.48 × 10-4). CONCLUSION: This study has thoroughly investigated previous GWAS to pinpoint variants that may play a causal role in poor schizophrenia treatment outcomes, and provides potential candidate genes for further study in the field of antipsychotic response.

Patient-oriented randomisation: A new trial design applied in the Neuroleptic Strategy Study.

BACKGROUND: The 'gold standard' for clinical studies is a randomised controlled trial usually comparing specific treatments. If the scientific study expands to strategy comparison with each strategy including various treatments, the research problems are increasingly complicated. The strategy debate in the psychiatric community is the starting point for the development of our new design. It is widely accepted that second-generation antipsychotics are the therapy of choice in the treatment of schizophrenia. However, their general superiority over first-generation antipsychotics could not be demonstrated in recent randomised controlled trials. Furthermore, we are becoming increasingly aware that the experimental conditions of randomised controlled trials, as in the European First Episode Schizophrenia Trial and Clinical Antipsychotic Trials of Intervention Effectiveness Phase 1 studies, may be inappropriate for psychiatric treatments. The high heterogeneity in the patient population produces discrepancies between daily clinical perception and randomised controlled trials results. The patient-oriented approach in the Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study reflects everyday clinical practice. The results, however, are highly dependent on the physicians' preferences. The goal of the design described here is to take an intermediate path between randomised controlled trials and clinical studies such as Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study, combining the advantages of both study types. METHODS: The idea is to randomise two treatment pairs each consisting of one first-generation antipsychotic and one second-generation antipsychotic in a first step and subsequently, to involve the investigators in deciding for a pair most appropriate to the patients' needs and then to randomise the allocation to one drug (first-generation antipsychotic or second-generation antipsychotic) of that chosen pair. This idea was first implemented in the clinical trial, the Neuroleptic Strategy Study, with a randomised design comparing efficacy and safety of two different strategies: either to use first-generation antipsychotics (haloperidol and flupentixol) or second-generation antipsychotics (olanzapine, aripiprazole and quetiapine) in patients suffering from schizophrenia. RESULTS: In the course of the Neuroleptic Strategy Study, feasibility of this design was demonstrated. All aspects of the new design were implemented: randomisation process, documentation of responses from investigators as well as patients and drug logistic experience. In implementing the design, furthermore, we could investigate its theoretical properties. The physicians' preferences for specific drugs used for the respective patients were analysed. CONCLUSION: The idea of patient-oriented randomisation can be generalised. In light of the heterogeneity and complexity of patient-drug interaction, this design should prove particularly useful.

Combining depot antipsychotic with an assertive monitoring programme for treating first-episode schizophrenia in a resource-constrained setting.

AIM: To assess the feasibility and effectiveness of depot antipsychotic (flupenthixol decanoate) combined with an assertive monitoring programme (AMP) in first-episode schizophrenia. METHODS: This was a prospective, non-comparative, longitudinal study conducted over 12 months assessing patient acceptance, adherence, outcome in domains of psychopathology, functionality and quality of life, and tolerability. RESULTS: Of 207 participants, 149 (72%) completed 12 months of treatment. Acceptance of and adherence to depot was good. Treatment response was achieved by 170 (82%) participants and remission by 124 (60%). Thirty-three (19%) responders relapsed and 10 (5%) participants met a priori criteria for treatment resistance. Treatment was generally well tolerated. CONCLUSIONS: Combination of depot antipsychotic with an AMP may be an effective and safe intervention in early phases of schizophrenia, and may be particularly suitable for resource-constrained settings.