CPRD StudyPrimary Care PASS Study

Defining risk profiles in special populations -results from a post authorisation safety study of Seroquel XL© conducted in England

D. Layton, V. Osborne, M. Davies, S. Shakir


A risk management plan of quetiapine extended release (XL) had a need to describe use & monitor long-term (12+ months) safety in the primary care setting. Its aim was to monitor for known risks (e.g. metabolic effects) and safety signals in patients of all indications. One of the study objectives included monitoring specials populations who may be more vulnerable to risks due to past medical history and/or concurrent conditions or medication use.
Aim: To describe risk profiles of special population groups (by indication, past medical history, prior psychoactive drugs, and age ≥65,<64 years)


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


An observational, single-exposure cohort design. Data were derived on exposure from dispensed prescriptions; on events from forms completed by physicians 12 months post first exposure. For general surveillance crude incidence densities (ID) per 1000 patient-months were calculated for events in months (m) 1, m2-6, m7-12 and m1-12 inclusive for cohort, and by special population group. Overdose events were grouped by suicidal ideation, suicidal behaviour, self- injurious behaviour. Event ID differences (IDD m1- m2-6 ) + 95%CI excluding the null (0) were signals of starting treatment. Survival methods estimated rates of overdose and hyperglycaemic events (+95%CI) per 1000 patient-months (where n>7 and excluding patients if event dates were missing).


Cohort comprised 13276 patients; 59% female; median age 43 (IQR 33,55). Events with highest ID m1-12 inclusive were: Sedation, n=317: ID 40; Somnolence,n=288: ID 47; and Weight increased,n=198: ID 54. Somnolence & Sedation were associated with starting treatment overall (IDD m1-m2-6 :3.8(1.5,5.7) and 2.5(0.8,4.2) respectively) and in special population groups with Bipolar Bisorder or Non-licensed (off-label) indications; age ≤64 years; and a history of depression. For hyperglycaemic events, the highest rates in months 1-12 inclusive were: raised random blood sugar (n=122):1.0 (0.8,1.2) and raised fasting plasma glucose (n=104):0.8 (0.7,1.0). Patients with a history of impaired glucose tolerance and diabetes appeared to have highest rates of hyperglycaemic events.Of 104 overdose events, a history of mental illness was reported for all patients; event rates in months 1-12 inclusive were: suicidal behaviour(n=84):101.8 (82.2,126.1), suicidal ideation (n=1):4.0 (0.6,28.4), and self-injurous behaviour (n=15): 36.6 (22.0,60.1).


For frequently reported central nervous system, psychiatric and hyperglycaemic events, many patients had pre-existing risk factors that are likely to put them at elevated risk. This study demonstrates the ongoing importance of observational studies to support the risk:benefit evaluation of medications.