D. Layton, S. Clarke, I. Ratcliffe, S. Shakir, T. Hale
The Observational Assessment of Safety in Seroquel (OASIS) study (ENCePP Study reg.5412) aimed to extend the post-authorisation safety knowledge of quetiapine extended release (Seroquel XL©) in the mental health secondary care setting, as prescribed by psychiatrists in new user adult (>18 years) patients with Schizophrenia or Bipolar Disorder compared to quetiapine immediate release (IR). The primary focus was on short-term (12-week) safety and high dose (>600mg/day) use.
To quantify event incidence and pattern after starting treatment and compare common event rates between users defined by dose and formulation.
An observational cohort design using Specialist Cohort Event Monitoring (SCEM). Questionnaires completed by specialists collected data on patient characteristics, exposure and events between December 2009 and December 2012. Exposure (patient-weeks) was calculated for: total cohort and sub-group stratified by formulation. Period specific exposures were calculated for three 4-week periods for total cohort. Period specific exposures were further stratified by formulation and high dose use (where >600mg/day for >50% of each 4-week period). Crude event Incidence Densities (ID) per 1000 patient-weeks and ID differences (IDD+95%CI) were calculated within and between groups over total study period and 4 week exposure periods ; IDD 95%CI excluding the null (0) were considered signals of events associated with starting treatment and/or high dose.
SCEM cohort comprised 845 patients; 471 (59%) were female and median age was 39 years (IQR 29,49); 40% (n=338) had Schizophrenia, 52% (n=442) had Bipolar disorder; 8% (n=65) had Other indications. High dose use was reported for 4% (28/631) in XL group and <1% (3/214) in IR group. The most frequently reported events weeks 1-12 inclusive (not associated with indication) were: sedation:ID 24, somnolence:ID 20, akasthesia: ID 3, and parkinsonism: ID 2. In the XL group, the IDDs for these 4 events were non-significantly lower for high vs standard dose for total study period and weeks 1-4. Within XL high dose group, sedation and somnolence were associated with starting treatment (IDD w1-4 – w5-8 : 25 (7,42) and 14 (14, 15) respectively); this pattern was also observed within XL and IR standard dose groups. Low counts in high dose group and IR cohort precluded reliable comparisons.
This study found that sedation & somnolence were common events associated with starting treatment, but not with high dose. Although the frequency of high dose use was low, OASIS provides important information on the safety and utilisation of Seroquel XL©.