D. Layton, V. Osborne, M. Davies, I. Ratcliffe, S. Clarke, S. Shakir, J. Reilly, A. Hale

Background

UK guidelines state that the lowest possible dose of antipsychotics should be used and titrated to the lowest effective dose. A risk management plan of quetiapine extended release (Seroquel XL©) had a need to describe long-term (12+ months) and short term (12 weeks) use and safety in primary and mental-health care setting, respectively. An M-PEM study monitored use and safety in all indications. A SCEM study monitored early-onset use and safety during Seroquel XL© titration and at higher doses (>600mg) in Schizophrenia and Bipolar Disorder adults (>18 years); a comparator group (immediate release quetiapine) was also included (ENCEPP Study 5412). M-PEM and SCEM study objectives included exploring posology.

Objectives

An adhoc analysis to describe prevalence of potential underdosing in clinical practice.

Methods

Exposure, selected prior medical history and medications use data were collected for each study from forms sent to hospital specialists for SCEM December 2009 to December 2012 and to primary care physicians (GPs) for M-PEM September 2008 to February 2013. Descriptive statistics were calculated; doses were converted to percentage of relevant maximum dose according to each indication and titration stage as specified in the Summary of Prescribing Characteristics (SPC).

Results

In the M-PEM cohort (N=13276), at start of treatment potential underdosing was calculated for: 37%(785/2136) Schizophrenia patients, 3% (98/3500) Bipolar Disorder patients, and 6%(147/2646) patients with Major Depressive Disorder. At date maintenance treatment regimen was reportedly achieved, potential underdosing was calculated for 38% (509/1339) Schizophrenia patients, 33% (721/2165) Bipolar Disorder patients, and 32% (531/1648) with Major Depressive Disorder. In the SCEM XL cohort (n=646), at start of treatment potential underdosing was calculated for 56% (144/258) Schizophrenia patients and 59% (204/345) Bipolar Disorder patients. At date maintenance treatment regimen was reportedly achieved, potential underdosing was calculated for 86% (223/258) Schizophrenia patients and 91% (315/345) Bipolar Disorder patients

Conclusion

Both studies found that potential underdosing occurred very commonly in all indications studied. 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 M-PEM is that patients treated by specialists may require more individualised therapy (including use of immediate release quetiapine) to initially stabilise their condition, whilst GPs tend to manage patients at later stages. Further work will explore impact of age and prior/concurrent psychotropic use on underdosing.