Deborah Layton, Vicki Osborne, Miranda Davies, Saad Shakir
A Risk Management Plan developed for quetiapine extended release (Seroquel XL©), included a PASS to examine its safety and use as prescribed in primary care. Objectives incl. exploring risks in special populations (SP).
To describe risk profiles by SP groups (indication, past medical (pmh) history, prior psychoactive drugs, and age >65,<64).
An observational, single-exposure cohort design. Data were derived on exposure from dispensed prescriptions; on events from forms completed by physicians 12 months (m) post first exposure. For general surveillance crude incidence densities (ID) per 1000 pt-m were calculated for events in m1, 2-6, 7-12 and 1-12 for cohort, and by SP group. Overdose events were grouped by suicidal ideation (SI), suicidal behaviour (SB), self-injurious behaviour (SIB). Event ID differences (IDD 1- 2-6 ) + 95%CI excluding the null (0) were signals of starting treatment. Survival methods estimated rates of overdose and hyperglycaemic (HG) events (+95%CI) per 1000 pt-m (where n>7 and excl pts if event date missing).
Cohort=13276; 59% female; median age 43 (IQR 33,55). Events with highest ID 1-12 were: Sedation, n=317: ID 40; Somnolence,n=288: ID 47; and Weight increased,n=198: ID 54. Somnolence and Sedation were associated with starting treatment overall (IDD 1-2-6 :3.8(1.5,5.7) and 2.5(0.8,4.2) respectively) and in SP groups: Indication Bipolar Bisorder or Non-licensed indications; age ≤64; and pmh depression. For HG events, the highest rates m 1-12 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). SP groups with pmh IGT and diabetes appeared to have highest rates.Of 104 overdose events, pmh mental illness was reported for all pts; event rates m 1-12 were: SB (n=84):101.8 (82.2,126.1), SI (n=1):4.0 (0.6,28.4), and SIB (n=15): 36.6 (22.0,60.1).
For frequently reported central nervous system, psychiatric and HG events, many pts 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.