102 - Summary

Summary

106 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 1 Penfluridol weekly Background Penfluridol is a diphenylbutylpiperidine FGA available in countries such as Brazil, China, India, Israel and the Netherlands and can be imported to other countries. Penfluridol is unusual in having a very long plasma half-­life – at least 60 hours.1 After oral administration, peak levels are reached within 12 hours and drug can still be detected 168 hours after a single oral dose.2 Its long duration of action seems to be a result of rapid distribution into fat tissue which acts as a drug reservoir.3 This property allows penfluridol to be used as a once-­weekly oral therapy for supervised ingestion – an alternative to long-­acting injectable antipsychotics. Clinical effectiveness Several trials have examined the use of once-­weekly oral penfluridol, in doses ranging from 5mg to 160mg per week.4 When given in this manner it is at least as effective as depot FGAs5,6 and may be better tolerated overall.4 A Dutch retrospective cohort study (n = 8,257) found that discontinuation trends for oral penfluridol and depot formulations were similar.7 In a small retrospective observational study of 19 patients (most of whom were treatment resistant), Dunnett and colleagues found just over half of the people prescribed penfluridol (n = 9) continued taking it during a 1-­year follow-­up,8 suggesting some efficacy in these patients. Although the dose–response relationship remains unclear, a weekly dose of 30mg is thought to be adequately effective,9 although a dose of 120mg a day (that is, a total of 840mg a week) has been used.10 Steady-state levels and plasma elimination half-­lives of people taking penfluridol can vary significantly, probably because of differences in adiposity.3 An early study found that a loading dose regimen (first dose 80mg; a total of 200mg over the first week) is effective and well tolerated11 but this regimen remains unlicensed and untested in larger studies. Penfluridol is probably underused considering the high rates of non-­adherence with oral antipsychotics and the reluctance to prescribe depots.12 Adverse effects Adverse effects include acute EPS, increased prolactin and TD, as might be expected.8 It is usually not sedative. Like pimozide (another diphenylbutylpiperidine), penfluridol appears to prolong the QT interval.13 Penfluridol is a cytotoxic agent which may have anticancer properties.14 Summary ■ ■Penfluridol can be given orally once a week. ■ ■Supervised weekly administration is at least as effective as long-­acting injections. ■ ■The usual dose is 20–40mg a week, but much higher doses have been used. ■ ■Adverse effects are those common to FGAs and include QT prolongation. ■ ■Sedation is minimal.