Lamotrigine

TIME is defined as being the time from entry into the randomized double-blind phase to the time of the first prescription of any additional pharmacotherapy or Electroconvulsive therapy (ECT) determined by the investigator to be necessary for treatment of a relapse and/or recurrence of a depressive, manic, hypomanic or mixed episode, whichever occurs first. TIME was measured relative to randomization date. Par. prematurely discontinued from the study prior to reaching the TIME event were censored at the time of discontinuation. Analysis was performed using Cox proportional hazards regression model with covariates of site, CGI-S baseline score, treatment and treatment by CGI-S baseline score interaction. The overall hazard ratio for treatment group could not be calculated due to different CGI-S baseline score level.

The CSS is the sum of items 9 (values: 1=Extremely difficult - 7=Extremely easy), 10 (same set of values as for 9), and 11 (1=Extremely inconvenient - 7=Extremely convenient). The sum has 3 subtracted from it, is divided by 18, and then multiplied by 100; the range is 0-100. Change from baseline=end of study CSS minus baseline score.

The time from randomization to the time at which the participant was withdrawn from the Double-Blind Phase of the study for any reason was measured. No data are reported for the Lamotrigine group because of an incalculable confidence interval. See the outcome measure entitled "Number of Participants with a Withdrawal Event" for data regarding the number of participants who withdrew from the study.

An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or causes its prolongation, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. A complete list of all SAEs and AEs experienced in the study can be found in the SAE/AE section.

The percentage of participants prematurely discontinuing the study was calculated as the number of participants who discontinued the study divided by the number who reached Visit 5 minus major protocol violators. The Control group is composed of data from other similar studies and is not part of this study.

Percent change from baseline is calculated as the number of seizures by week during the Double-Blind Treatment Phase (Treatment Week 1 up to Week 19) compared to the number of seizures per week during the Baseline Phase (Baseline Week 1 up to Week 8). A positive number equals a reduction in seizure frequency. PGTC seizures are more commonly known as gran mal seizures.

This measure has 11 items. The purpose of each item is to rate the severity of that abnormality in the patient. A severity rating is assigned to each of the eleven items, based on the patient's subjective report of his or her condition over the previous forty-eight hours and the clinician's behavioral observations during the interview, with the emphasis on the latter. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. Total score of zero to 60 is possible, zero being normal and 60 being severe, 12 serving as a cut off point for illness if equal or above. There are several ways to show change in outcome. The mean and standard deviation at week 0, 8 and 14 will indicate if there is a change in the scores with the treatment.

Blood samples for PK analysis will be collected on Days 1, 14, 28, and 42 before dosing (pre-dose) and at 0.5,1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 hours after administration. Other blood samples will be taken at 1 and 3 hours post dose on Day 15, and at 2 and 4 h post dose on Day 29. Additional blood samples will be taken at 48, 72, 96, 120, 168 and 216 hours after the administration of last dose on Day 42. Area under the concentration-time curve for a dose interval (AUC \[0-tau{24 hours}\]); observed maximum concentration (Cmax); and accumulation ratios (Rcmax and Ro) will be determined from the serum concentration-time data. Accumulation ratio will be calculated as follows: Ro = AUC(0-24) of Day14/AUC(0-24) of Day 1; and Rcmax = Cmax of Day14 / Cmax of Day 1

Steady-state Cmax and AUC (0-t) of atorvastatin when dosed to steady-state.