Estimating the optimal dose of flupentixol decanoate in the maintenance treatment of schizophrenia—a systematic review of the literature

Bailey, Loren; Taylor, David

doi:10.1007/s00213-019-05311-2

Cited by 13 publications

(7 citation statements)

References 46 publications

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“…The initial and maintenance dose of flupentixol decanoate for most patients is 20–40 mg every 2–3 weeks [ 45 ]. Although the recommended dose range of flupentixol decanoate is broad, recent evidence suggests that doses close to or below the minimum recommended dose (as low as 10 mg every 2 weeks) are effective [ 47 ]. Flupentixol is predominantly metabolized by sulfoxidation and lacks interactions associated with CYP inducers or inhibitors [ 45 ].…”

Section: First-generation Long-acting Injectable (Lai) Antipsychoticsmentioning

confidence: 99%

Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview

et al. 2021

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The availability of long-acting injectable (LAI) antipsychotics for the treatment of schizophrenia provides clinicians with options that deliver continuous drug exposure and may improve adherence compared with daily oral antipsychotics. However, all LAI antipsychotics have unique formulations and pharmacokinetic characteristics that have implications for medication selection, administration interval, and injection site. This review outlines key differences in drug formulations and pharmacokinetics among LAI antipsychotics. A systematic search of the PubMed database was conducted to identify physical and formulation properties and pharmacokinetic data of commercially available LAI antipsychotics, including flupentixol decanoate, fluphenazine decanoate, haloperidol decanoate, zuclopenthixol decanoate, aripiprazole monohydrate, aripiprazole lauroxil, olanzapine pamoate, paliperidone palmitate, risperidone microspheres, and risperidone polymeric microspheres. Additional information was obtained from package inserts and product monographs. Relevant data on drug properties, administration details, pharmacokinetic parameters, and oral dose equivalencies of LAI antipsychotics are summarized. Based on our analysis, formulation characteristics (e.g., vehicle medium) and administration characteristics (e.g., injection site) can affect rate of absorption and adverse effects and may factor into whether oral supplementation or an additional injection is needed. Dose adjustments may be necessary based on potential drug–drug interactions, and approximate dose equivalence with oral formulations can help inform titration when switching from oral to LAI formulations. Clinicians administering LAI antipsychotics should consider these formulation and pharmacokinetic factors to maximize clinical impact and to adjust to an individual patient’s needs and treatment goals. Supplementary Information The online version contains supplementary material available at 10.1007/s40263-020-00779-5.

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Section: First-generation Long-acting Injectable (Lai) Antipsychoticsmentioning

confidence: 99%

Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview

et al. 2021

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“…It has been suggested that these wide dosage ranges are not supported by the available evidence and may lead to some patients receiving unnecessarily high doses. For example, it has been proposed that the optimal dose of LAI flupentixol is probably between 20 mg and 40 mg every 2 weeks 19 ; we found that one in five prescriptions for this LAI antipsychotic medication were for doses above this upper threshold, thus potentially leading to an increased side-effect burden for little additional therapeutic benefit. The evidence suggests that most of the common side effects of antipsychotic medication, including EPS, are dose-related.…”

Section: Discussionmentioning

confidence: 74%

“…The prescribed dose of LAI flupentixol was greater than the suggested optimal dose of 20–40 mg every 2 weeks in 224 (19%) cases. 19 …”

Section: Resultsmentioning

confidence: 99%

“…Almost all (n = 560; 99%) of the LAI aripiprazole prescriptions were for monthly administration and, of these, 479 (86%) were for a dose of The prescribed dose of LAI flupentixol was greater than the suggested optimal dose of 20-40 mg every 2 weeks in 224 (19%) cases. 19 An assessment of side effects had been documented in the past year in 2304 (45%) cases.…”

Section: Resultsmentioning

confidence: 99%

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Side-effect monitoring of continuing LAI antipsychotic medication in UK adult mental health services

Paton

Craig

McConnell

et al. 2021

Therapeutic Advances in Psychopharmacology

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Background: Long-acting injectable (LAI) antipsychotic medications are used to optimise treatment outcomes in schizophrenia. Guaranteed medication delivery increases the responsibility of prescribers to monitor and manage adverse effects. Methods: In the context of a quality improvement programme conducted by the Prescribing Observatory for Mental Health, a clinical audit addressed documented side-effect monitoring in patients prescribed continuing LAI antipsychotic medication under the care of United Kingdom adult mental health services. Results: A total of 62 mental health services submitted data on 5169 patients prescribed LAI antipsychotic medication for more than a year. An assessment of side effects had been documented in the past year in 2304 (45%) cases. Post hoc analysis showed that extrapyramidal side effects were more likely to have been assessed and found to be present in those patients prescribed LAI haloperidol, flupentixol or zuclopenthixol. There was little other targeting of assessments to the known side effects profiles of individual LAI antipsychotic medications, but when dysphoria had been assessed it was most commonly found with LAI haloperidol treatment and when weight gain, sexual and prolactin-related side effects had been assessed, they were more often identified with LAI paliperidone. Conclusion: The data suggest a relatively low frequency of side-effect assessments, largely untargeted. This is likely to result in many adverse effects going unrecognised and unmanaged, thus failing to tackle their potential to confound mental state assessment and adversely affect physical health and adherence. Patients receiving LAI antipsychotic medication have regular contact with a healthcare professional who administers the medication, which provides an opportunity to potentially remedy this situation.

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“…However, it is noted that previous dose-response Calculations were derived using references listed in Table 1 (Kegeles et al, 2008;Nyberg et al, 1995;Reimold et al, 2007). studies for flupentixol decanoate suggest that doses above 40 mg/ fortnight may not result in any additional benefit seen (Bailey and Taylor, 2019).…”

Section: Resultsmentioning

confidence: 99%

A proposal for reducing maximum target doses of drugs for psychosis: Reviewing dose–response literature

O’Neill,

Jameson,

McLean

et al. 2024

J Psychopharmacol

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Background: Presently, there is limited guidance on the maximal dosing of psychosis drugs that is based on effectiveness rather than safety or toxicity. Current maximum dosing recommendations may far exceed the necessary degree of dopamine D2 receptor blockade required to treat psychosis. This may lead to excess harm through cognitive impairment and side effects. Aims: This analysis aimed to establish guidance for prescribers by optimally dosing drugs for psychosis based on efficacy and benefit. Methods: We used data from two dose–response meta-analyses and reviewed seven of the most prescribed drugs for psychosis in the UK. Where data were not available, we used appropriate comparison techniques based on D2 receptor occupancy to extrapolate our recommendations. Results: We found that the likely threshold dose for achieving remission of psychotic symptoms was often significantly below the currently licensed dose for these drugs. We therefore recommend that clinicians are cautious about exceeding our recommended doses. Individual factors, however, should be accounted for. We outline potentially relevant factors including age, ethnicity, sex, smoking status and pharmacogenetics. Additionally, we recommend therapeutic drug monitoring as a tool to determine individual pharmacokinetic variation. Conclusions: In summary, we propose a new set of maximum target doses for psychosis drugs based on efficacy. Further research through randomised controlled trials should be undertaken to evaluate the effect of reducing doses from current licensing maximums or from doses that are above our recommendations. However, dose reductions should be implemented in a manner that accounts for and reduces the effects of drug withdrawal.

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Estimating the optimal dose of flupentixol decanoate in the maintenance treatment of schizophrenia—a systematic review of the literature

Cited by 13 publications

References 46 publications

Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview

Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview

Side-effect monitoring of continuing LAI antipsychotic medication in UK adult mental health services

A proposal for reducing maximum target doses of drugs for psychosis: Reviewing dose–response literature

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