Flupentixol 40mg/2ml solution for injection ampoules

RATIONALE: The licensed dose range for the long-acting injectable antipsychotic flupentixol decanoate (Depixol®) in the treatment of schizophrenia is very broad. This provides little useful direction to prescribers and may ultimately result in patients receiving unnecessarily high doses. OBJECTIVES: We aimed to estimate the effect of dose of flupentixol decanoate on relapse rates in schizophrenia and on tolerability by expanding on an earlier review and including non-RCT and German-language studies, as well as using pharmacokinetic and pharmacodynamic data to offer guidance on dosing. METHODS: A literature review using EMBASE, Medline, PsycINFO and PubMed was conducted. Treatment success rates at 6 months were extracted or extrapolated from the studies and plotted against dose to estimate a dose-response curve. RESULTS: Data from 16 studies (n = 514) allowed estimation of a dose-response curve which rises steeply between the chosen placebo anchor (25% success rate) and 10 mg every 2 weeks before reaching a maximum between 20 and 40 mg every 2 weeks (80-95% success rates). Extrapyramidal side effects (EPSEs) were frequently seen (12-71% of participants) in that dose range. Two -weekly injections seem to provide the highest trough plasma concentration per dose administered and the lowest peak-to-trough concentration ratio. Plasma concentration varied up to 5-fold among individuals receiving the same dose. CONCLUSIONS: The optimal dose of flupentixol decanoate is likely to be between 20 mg and 40 mg every 2 weeks although higher doses may be required in some individuals owing to variation in drug handling. Doses of flupentixol should be individually established in the range of 10 to 40 mg every 2 weeks according to response and tolerability.

Abstract licence: CC BY 4.0

Summary Background The antitussive potential of flupentixol-melitracen, an anti-anxiety and anti-depression compound, has been observed previously. We aimed to further evaluate its efficacy and safety in patients with refractory chronic cough (RCC) who were unresponsive to any other available treatments. Methods This randomised, double-blinded, placebo-controlled clinical trial was conducted at a single specialist cough clinic in Tongji Hspital, Shanghai, China. Adults aged 18–69 years with RCC and persistent cough despite at least two weeks of neuromodulator therapy were enrolled. Participants were randomly assigned (1:1) to receive either oral flupentixol-melitracen (flupentixol 0.5 mg + melitracen 10 mg), one tablet twice daily, or matching placebo, for two weeks, followed by a one week of off-treatment safety monitoring. Randomisation was computer-generated, with masking of participants, investigators, and outcome assessors. The co-primary endpoints were cough resolution rate (≥50% reduction in cough symptom score [CSS]) at visit four and placebo-adjusted change in CSS over time. The full analysis set (FAS) was used following the modified intention-to-treat (mITT) principle for demographic baseline analysis and efficacy analysis. The safety set (SS) was used for safety analysis and included all patients who took at least one dose of treatment and had post-dose safety records. The FAS and SS were equivalent in this study. The trial is registered with the Chinese Clinical Trial Registry, ChiCTR2000035304. Findings Between March 9th, 2021 and December 1st, 2023, 102 patients were enrolled and randomised. A total of 99 patients received at least one dose of treatment and were included in the primary and safety analyses (49 taking flupentixol-melitracen and 50 taking placebo). At visit four, flupentixol-melitracen arm reached significantly higher cough resolution rate (65.3% [32/49] vs 32.0% [16/50]; p = 0.0009). The adjusted mean reduction in CSS was 0.144 points greater in the flupentixol-melitracen group than in the placebo group over time (p = 0.0034). Treatment-emergent adverse events occurred in 51.0% (15/49) of patients in the flupentixol-melitracen group and 34.0% (17/50) in the placebo group. No serious adverse events or treatment-related deaths were reported. All adverse events were mild and resolved after discontinuation. Interpretation Our findings suggest that short-term use of flupentixol-melitracen may be an effective and well-tolerated treatment for RCC. However, the findings should be interpreted with caution due to key limitations, including the absence of objective cough frequency measurement and limited generalisability beyond a single-centre population. These factors may influence the precision and applicability of the observed treatment effect. Further trials using objective endpoints and longer follow-up in broader populations are needed to confirm efficacy and safety. Funding The Project of 10.13039/501100003399Science and Technology Commission of Shanghai Municipality.

Abstract licence: CC BY