CPRD StudyPrimary Care PASS Study

Abstract 144: Potential for Underdosing of Antipsychotics (AP) in Primary and Mental Health Care: Findings from Post-Authorisation Safety Studies Conducted on Seroquel XL

Deborah Layton, Vicki Osborne, Miranda Davies, Ian Ratcliffe, Sarah Clarke, Saad AW Shakir, Joe Reilly, Tony Hale.


UK guidelines state that the lowest possible dose of APs should be used and titrated to the lowest effective dose. The Risk Management Plan for quetiapine extended release (Seroquel XL©) had a need to describe utilisation in primary care in all indications (via Modified Prescription-Event Monitoring (MPEM)-12 mths observation (obs)) and in the mental health setting in patients (pts) with schizophrenia (Schiz) or bipolar disorder (BD) (via Specialist Cohort Event Monitoring (SCEM)-12 weeks obs; ENCePP Study reg. 5412). Study objectives included exploring posology.


To describe dosing of Seroquel XL©, with a focus on potential for underdosing.


Exposure, selected prior medical history (pmh) and medications use data were collected for each study from forms sent to hospital specialists for SCEM Dec 2009 – Dec 2012 and to primary care physicians (GPs) for MPEM Sep 2008-Feb 2013, respectively. Descriptive statistics were calculated; doses were converted to % of relevant max dose by indication and titration stage in SPC– underdosing defined as <100%.


In the M-PEM (13276), potential underdosing was very common; start:Schiz:37%(785/2136); BD:3%(98/3500); Major Depressive Disorder (MDD):6%(147/2646); maint: Schiz: 38%(509/1339); BD:33%(721/2165); MDD: 32%(531/1648). In the SCEM (869) potential underdosing was also very common at start: Schiz:56%(144/258); BD:59%(204/305) and at maint (86% (223), and 91% (315) respectively).


Both studies found that potential underdosing occurred for all indications. Start dose data correlated poorly with SPC and expert guidelines to use lowest effective dose, but corresponded to UK prescribing guidelines which do not recommend excessive doses, unless other evidence–based strategies have failed. Possible explanations for more common potential underdosing in SCEM vs MPEM is that pts treated by specialists may require more individualised therapy (incl use of immediate release quetiapine) to initially stabilise their condition, whilst GPs tend to manage pts at later stages. Further work will explore impact of age and prior/concurrent psychotropic use on underdosing.