6 ADVERSE REACTIONS

6.1 Clinical Studies Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

The information below is derived from a clinical trial database for SEROQUEL XR consisting of approximately 3400 patients exposed to SEROQUEL XR for the treatment of Schizophrenia, Bipolar Disorder, and Major Depressive Disorder in placebo-controlled trials. This experience corresponds to approximately 1020.1 patient-years. Adverse reactions were assessed by collecting adverse reactions, results of physical examinations, vital signs, body weights, laboratory analyses and ECG results.

Adverse reactions during exposure were obtained by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping similar types of reactions into a smaller number of standardized event categories. In the tables and tabulations that follow, standard MedDRA terminology has been used to classify reported adverse reactions.

The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline eva luation.

Adverse Reactions Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlled Trials

Schizophrenia: There was no difference in the incidence and type of adverse reactions associated with discontinuation (6.4% (61/951) for SEROQUEL XR vs. 7.5% (24/319) for placebo) in a pool of controlled Schizophrenia trials. There were no adverse reactions leading to discontinuation that occurred at an incidence of ≥ 2% for SEROQUEL XR in Schizophrenia trials.

Bipolar Disorder:

Mania: In a single clinical trial in patients with bipolar mania, 4.6% (7/151) of patients on SEROQUEL XR discontinued due to adverse reaction compared to 8.1% (13/160) on placebo. There were no adverse reactions leading to discontinuation that occurred at an incidence of ≥ 2% for SEROQUEL XR in Bipolar Mania trials.

Depression: In a single clinical trial in patients with bipolar depression, 14% (19/137) of patients on SEROQUEL XR discontinued due to adverse reaction compared to 4% (5/140) on placebo. Somnolence∗ was the only adverse reaction leading to discontinuation that occurred at an incidence of ≥ 2% in SEROQUEL XR in Bipolar Depression trials.
∗ The adverse reaction term “somnolence” includes both “somnolence” and “sedation.”
MDD, Adjunctive Therapy: In adjunctive therapy clinical trials inpatients with MDD, 12.1% (76/627) of patients on SEROQUEL XR discontinued due to adverse reaction compared to 1.9% (6/309) on placebo. Somnolence* was the only adverse reaction leading to discontinuation that occurred at an incidence of ≥ 2% in SEROQUEL XR in MDD trials.

Commonly Observed Adverse Reactions in Short-Term, Placebo-Controlled Trials:

In short-term placebo-controlled studies for schi