Abstract
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 10mg every 2 weeks before reaching a maximum between 20 and 40mg every 2 weeks (80-95% success rates). EPSE 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 20mg and 40mg 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 10mg to 40mg every 2 weeks according to response and tolerability.
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 10mg every 2 weeks before reaching a maximum between 20 and 40mg every 2 weeks (80-95% success rates). EPSE 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 20mg and 40mg 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 10mg to 40mg every 2 weeks according to response and tolerability.
| Original language | English |
|---|---|
| Journal | Journal of Psychopharmacology |
| Publication status | Accepted/In press - 11 Jun 2019 |