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.

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.

Bioequivalence Study Of A Fixed-Dose Combination Tablet Containing Melitracen 10 mg And Flupentixol 0.5 mg In Healthy Chinese Volunteers Under Fasted And Fed Conditions.

PURPOSE: A fixed-dose combination (FDC) tablet of melitracen/flupentixol has been widely used for depression. The purpose of this study was to assess the safety profile and the relative bioavailability of two FDC products containing 10 mg melitracen and 0.5 mg flupentixol from two different manufacturers, in order to acquire adequate pharmacokinetic evidence for registration approval of the test formulation. METHODS: The study was designed as a single-dose, randomized, open-label, 2-period crossover study under fasted or fed conditions in healthy Chinese subjects. Twenty-four subjects (16 men and 8 women) were selected for fasted study, and another 24 cases (16 men and 8 women) were in fed study. Each subject was randomized at the beginning to receive either a single dose of the reference FDC or the test FDC tablet during the first period. Following two-week washout period, all subjects received the alternate formulation during the second period. Blood samples were collected up to 144 hrs after administration. Pharmacokinetic parameters, including Cmax, Tmax, AUC0-t, AUC0-∞, t½, CL/F, and Vd/F were acquired based on the time versus concentration profiles. Then, the geometric mean ratios (GMR) and corresponding 90% CIs were calculated for the determination of bioequivalence analysis. Safety assessment included changes in vital signs and laboratory tests, physical examination findings, and incidence or reports of adverse events (AEs). RESULTS: The present study has clearly indicated the test and the reference FDC products are bioequivalent in terms of rate and extent of drug absorption. GMR of Cmax, AUC0-t, and AUC0-∞ for both flupentixol and melitracen between the two formulation FDC products, and corresponding 90% CIs, were all within the range of 80% to 125% under fasted or fed conditions. Both the test and the reference FDC products indicated good tolerance in all volunteers. Chinese Clinical Trials Registry identifier: CTR20171256.

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.

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.

Crystalline retinopathy association with flupentixol intake.

AIM: To report the first case report of an association between flupentixol and crystalline retinopathy. STUDY DESIGN: Observational, Case report. CASE REPORT: We report a case of crystalline retinopathy in a 36-year-old female who was suffering from depression and being treated with tablet flupentixol in a cumulative dose of 4380 mg over two years. Fundus examination of both eyes showed multiple, discrete, yellowish white refractile intraretinal deposits over the macula and peripapillary region, located in the inner retina as shown by OCT. CONCLUSION: We propose regular retinal evaluation in patients with chronic flupentixol intake and larger studies to establish causal relationship between flupentixol and crystalline retinopathy.

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.

Changes in brain regions associated with food-intake regulation, body mass and metabolic profiles during acute antipsychotic treatment in first-episode schizophrenia.

We investigated whether morphological brain changes occurred in brain regions associated with body-weight homeostasis during acute antipsychotic treatment, and if so, whether they were related to changes in body mass and metabolic profile. Twenty-two antipsychotic-naive patients with first-episode schizophrenia received either risperidone long acting injection or flupenthixol decanoate over 13 weeks and were compared by structural MRI with 23 matched healthy volunteers at weeks 0, 4 and 13. Images were reconstructed using freesurfer fully-automated whole brain segmentation. The ventral diencephalon and prefrontal cortex were selected to represent the homeostatic and hedonic food intake regulatory systems respectively. Body mass was measured at weeks 0, 7 and 13 and fasting glucose and lipid profiles at weeks 0 and 13. Linear mixed effect models indicated significant group(⁎)time interactions for the ventral diencephalon volumes bilaterally. Ventral diencephalon volume reduction was strongly correlated bilaterally with body mass increase and HDL-cholesterol reductions, and unilaterally with blood glucose elevation. There were no significant changes in prefrontal cortical thickness. These findings implicate the ventral diencephalon, of which the hypothalamus is the main component, in the acute adipogenic and dyslipidaemic effects of antipsychotic medication.

Effect of clinician-patient communication on compliance with flupentixol-melitracen in functional dyspepsia patients.

AIM: To explore whether clinician-patient communication affects adherence to psychoactive drugs in functional dyspepsia (FD) patients with psychological symptoms. METHODS: A total of 262 FD patients with psychological symptoms were randomly assigned to four groups. The patients in Groups 1-3 were given flupentixol-melitracen (FM) plus omeprazole treatment. Those in Group 1 received explanations of both the psychological and gastrointestinal (GI) mechanisms of the generation of FD symptoms and the effects of FM. In Group 2, only the psychological mechanisms were emphasized. The patients in Group 3 were not given an explanation for the prescription of FM. Those in Group 4 were given omeprazole alone. The primary endpoints of this study were compliance rate and compliance index to FM in Groups 1-3. Survival analyses were also conducted. The secondary end points were dyspepsia and psychological symptom improvement in Groups 1-4. The correlations between the compliance indices and the reductions in dyspepsia and psychological symptom scores were also evaluated in Groups 1-3. RESULTS: After 8 wk of treatment, the compliance rates were 67.7% in Group 1, 42.4% in Group 2 and 47.7% in Group 3 (Group 1 vs Group 2, P = 0.006; Group 1 vs Group 3, P = 0.033). The compliance index (Group 1 vs Group 2, P = 0.002; Group 1 vs Group 3, P = 0.024) with the FM regimen was significantly higher in Group 1 than in Groups 2 and 3. The survival analysis revealed that the patients in Group 1 exhibited a significantly higher compliance rate than Groups 2 and 3 (Group 1 vs Group 2, P = 0.002; Group 1 vs Group 3, P = 0.018). The improvement in dyspepsia (Group 1 vs Group 2, P < 0.05; Group 1 vs Group 3, P < 0.05; Group 1 vs Group 4, P < 0.01) and psychological symptom scores (anxiety: Group 1 vs Group 2, P < 0.01; Group 1 vs Group 3, P < 0.05; Group 1 vs Group 4, P < 0.01; depression: Group 1 vs Group 2, P < 0.01; Group 1 vs Group 3, P < 0.01; Group 1 vs Group 4, P < 0.01) in Group 1 were greater than those in Groups 2-4. The compliance indices were positively correlated with the reduction in symptom scores in Groups 1-3. CONCLUSION: Appropriate clinician-patient communication regarding the reasons for prescribing psychoactive drugs that emphasizes both the psychological and GI mechanisms might improve adherence to FM in patients with FD.

Changes in body mass and metabolic profiles in patients with first-episode schizophrenia treated for 12 months with a first-generation antipsychotic.

OBJECTIVES: To assess changes in body mass and metabolic profiles in patients with first-episode schizophrenia receiving standardised, assured treatment and to identify predictors and moderators of the effects. METHODS: We investigated the changes in body mass, fasting blood glucose and lipids in 107 largely antipsychotic naïve, first-episode schizophrenia patients who were treated according to a standard algorithm with long-acting injectable flupenthixol decanoate over 12 months. RESULTS: Eighty-three (78%) participants completed the 12 months of treatment, and 104 (97%) received 100% of the prescribed injections during their participation. There were significant increases in BMI (P<.0001), waist circumference (P=0.0006) and triglycerides (P=0.03) and decrease in HDL (P=0.005), while systolic (P=0.7) and diastolic blood pressure (P=0.8), LDL (P=0.1), cholesterol (P=0.3), and glucose (P=0.9) values did not change over time. The triglyceride: HDL ratio increased by 91%. Change in BMI was only correlated with change in triglycerides (P=.008). The only significant predictor of BMI increase was non-substance abuse (P=.002). CONCLUSIONS: The risks of weight gain and metabolic syndrome associated with antipsychotic treatment in first-episode schizophrenia are not restricted to second generation antipsychotics. This is a global problem, and developing communities may be particularly susceptible.

Pathological gambling induced by dopamine antagonists: a case report.

Pathological gambling is defined as inappropriate, persistent, and maladaptive gambling behaviour. It is a non-pharmacological addiction classified as an impulse control disorder. However, pathological gambling has been associated with dopamine agonist use. Here we report of a 28-year-old man with a first major depressive episode and a post-traumatic stress disorder who has been treated with a combination of the serotonine/noradrenaline reuptake inhibitor duloxetine and the tricyclic antidepressant maprotiline. The administration of antipsychotic flupentixole (up to 7 mg) turned this slight online poker gambler into an excessive gambler. Only after the discontinuation of the antidopaminergic agents and the switch to bupropion did this gambling behaviour stop which suggests a causal relationship between dopamine antagonists and pathological gambling.

Flupenthixol versus low-potency first-generation antipsychotic drugs for schizophrenia.

BACKGROUND: Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between antipsychotic drugs, however, low-potency antipsychotic drugs are sometimes perceived as less efficacious than high-potency compounds by clinicians, and they also seem to differ in their side effects. OBJECTIVES: To review the effects in clinical response of flupenthixol and low-potency antipsychotics for people with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (July 2010). SELECTION CRITERIA: Randomised controlled trials that compared flupenthixol with first-generation low-potency antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis. DATA COLLECTION AND ANALYSIS: We extracted data independently. For continuous data, we calculated mean differences (MD) based on a random-effects model. MAIN RESULTS: The review currently includes one randomised trial from mainland China with 153 participants that lasted two months and compared flupenthixol with chlorpromazine. The exact methods of sequence generation and allocation concealment were not reported, and medication was provided in an open manner. There were no data on the outcomes that we had a priori selected for a 'Summary of findings' table.There was no significant difference between flupenthixol and chlorpromazine in the participants' general mental state at endpoint as measured by the Brief Psychiatric Rating Scale (BPRS) total score (1 randomised controlled trial (RCT), n = 153, MD 2.20 95% confidence interval (CI) -1.25 to 5.65). Chlorpromazine was associated with significantly less dizziness (1 RCT, n = 153, MD 0.12 95% CI 0.01 to 0.23); dystonia (1 RCT, n = 153, MD 0.29 95% CI 0.13 to 0.45); unsteady gait (1 RCT, n = 153, MD 0.46 95% CI 0.28 to 0.64); reduced facial expression (1 RCT, n = 153, MD 0.27 95% CI 0.09 to 0.45); restlessness (1 RCT, n = 153, MD 0.69 95% CI 0.45 to 0.93); rigidity (elbow) (1 RCT, n = 153, MD 0.48 95% CI 0.28 to 0.68); and tremor (1 RCT, n = 153, MD 0.56 95% CI 0.34 to 0.78). Chlorpromazine produced more dryness of mouth than flupenthixol (1 RCT, n = 153, MD -0.14 95% CI -0.25 to -0.03). AUTHORS' CONCLUSIONS: The evidence base of flupenthixol versus low-potency first-generation antipsychotics is currently restricted to one randomised comparison with chlorpromazine. The few reported data do not suggest a difference in efficacy, but flupenthixol appeared to produce more movement disorders and dizziness, while chlorpromazine was associated with the anticholinergic side effect - dryness of mouth. More trials are needed to make conclusions about the relative effects of flupenthixol and low-potency antipsychotics.

Efficacy and safety of esomeprazole with flupentixol/melitracen in treating gastroesophageal reflux disease patients with emotional disorders.

BACKGROUND AND AIM: This study was designed to demonstrate the safety and efficacy of esomeprazole combined with flupentixol/melitracen for the treatment of gastroesophageal reflux disease (GERD) patients with emotional disorders. METHODS Two hundred eighty-nine GERD patients with emotional disorders were divided randomly into two groups: group 1 received esomeprazole only (monotherapy) and group 2 received esomeprazole and flupentixol/melitracen (combination therapy). The patients' GERD questionnaire (GerdQ) and hospital anxiety and depression (HAD) scores were obtained before and after treatment. Changes in the scores, rates of symptom remission, and adverse effects were compared between the two groups. RESULTS: After 2 weeks of treatment, the average decrease in GerdQ score in the combination group (4.04 ± 2.34) was significantly greater than that in the monotherapy group (3.34 ± 2.74; P < 0.05). Significant differences between the two groups were also found for changes in HAD anxiety scores (5.45 ± 2.41 vs 3.34 ± 2.43, P < 0.05), depression scores (5.47 ± 2.47 vs 3.00 ± 3.28, P < 0.05), and anxiety-depression scores (5.20 ± 2.71 vs 3.60 ± 2.56, P < 0.05). The remission of symptoms (eructation, abdominal pain, anorexia, and other accompanying symptoms) in the combination group was significantly better than that in the monotherapy group, and no significant difference in the incidence of adverse events was observed between the two groups. CONCLUSIONS: The combination therapy has better efficacy than the monotherapy in improving the symptoms of gastroesophageal reflux in patients with emotional disorders. In addition, this combination treatment is safe, with a low incidence of adverse events.

Flupentixol use and adverse reactions in comparison with other common first- and second-generation antipsychotics: data from the AMSP study.

This study compares the first-generation antipsychotic (FGA) flupentixol to haloperidol and common second-generation antipsychotics (SGAs) as to drug utilization and severe adverse drug reactions (ADRs) in clinical treatment of schizophrenia inpatients using data from the drug safety program Arzneimittelsicherheit in der Psychiatrie (AMSP). AMSP drug utilization and reported ADR data were analyzed. Type and frequency of severe ADRs attributed to flupentixol were compared with haloperidol, clozapine, olanzapine, quetiapine, risperidone and amisulpride in a total of 56,861 schizophrenia inpatients exposed to these drugs. In spite of increasing prescription of SGAs, flupentixol was consistently used in schizophrenic inpatients (about 5 %) over time. Reporting rates of severe ADR ranged from 0.38 to 1.20 % for the individual antipsychotics (drugs imputed alone); flupentixol ranked lowest. The type of ADR differed considerably; as to severe EPMS, flupentixol (0.27 %), such as risperidone (0.28 %), held an intermediate position between haloperidol/amisulpride (0.55/0.52 %) and olanzapine/quetiapine (<0.1 %). The study is a heuristic approach, not a confirmatory test. Flupentixol has a stable place in the treatment of schizophrenia in spite of the introduction of different SGAs. Comparative ADR profiles suggest an intermediate position between FGAs and SGAs for flupentixol in clinical practice.

Psychopharmacological treatment and course in paranoid personality disorder: a case series.

Little is known about the role of psychopharmacological treatment and course of illness in patients diagnosed with a paranoid personality disorder. This short communication provides a naturalistic study of a psychiatric hospital case series. Fifteen consecutive patients were retrospectively studied. The Clinical Global Impression was rated at first admission, at last psychiatric contact, and after a 6-week observation period with or without antipsychotic treatment. During psychiatric admissions, three patients improved markedly, eight showed only minor changes, and four worsened. In total, seven patients had been administered any antipsychotic medication. The median duration of treatment was 15 weeks (range 4 days-328 weeks). No major adverse effects were noted. Among patients with sixth-week observations available, four had received antipsychotics; they appeared to improve considerably compared with six patients who had not received antipsychotics. Although the findings should be interpreted with caution, they support the notion of the disorder being a relatively chronic condition, although antipsychotics appeared to be safe and possibly had an effect in the short term.

Metabolic syndrome and antipsychotic monotherapy treatment among schizophrenia patients in Malaysia.

OBJECTIVE: The objective of this study is to determine the prevalence of metabolic syndrome among schizophrenia patients receiving antipsychotic monotherapy in Malaysia. METHOD: A cross-sectional study was conducted at multiple centres between June 2008 and September 2011. Two hundred and five patients who fulfilled the DSM IV-TR diagnostic criteria for schizophrenia and who had been on antipsychotic medication for at least one year, were screened for metabolic syndrome. Patients receiving a mood stabilizer were excluded from the study. Metabolic syndrome was defined by using the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Treatment Panel III (ATP III) modified for Asian waist circumference. RESULTS: In the first-generation antipsychotic (FGA) group, the highest prevalence of metabolic syndrome was among patients treated with trifluoperazine and flupenthixol decanoate (66.7% each). For the second-generation antipsychotic (SGA) group, the highest prevalence of metabolic syndrome was among patients treated with clozapine (66.7%). The component with the highest prevalence in metabolic syndrome was waist circumference in both FGA and SGA groups except for aripiprazole in SGA. CONCLUSION: The prevalence of metabolic syndrome in schizophrenia patients receiving antipsychotic monotherapy in Malaysia was very high. Intervention measures are urgently needed to combat these problems.