A prospective multicenter open-label study of lamotrigine in patients with bipolar I disorder (GlaxoSmithKline protocol SCA40917) was performed at 188 sites in the United States. Institutional review board approval was obtained for each site, and all patients provided written informed consent before entering the study.
Subjects were enrolled on the basis of clinical judgment of the investigators. Patients were eligible to participate if they were 13 years or older and had been given a diagnosis, based on an unstructured clinical interview and review of available medical records, of bipolar I disorder according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.  Those currently being treated for bipolar disorder were eligible if they were being treated with a stable regimen of psychotropic medications that did not include lamotrigine and had been initiated at least 2 months before study entry. Mood state was not specified. Patients whom the study investigator judged to have a medical condition or severe psychiatric symptoms that could interfere with study participation were excluded. Female patients of childbearing age who were pregnant or breast-feeding or were capable of bearing children and not using adequate contraceptive methods were also excluded.
All participants in the study were to receive lamotrigine for 12 weeks, including a 5-week initiation/titration period and a 7-week continuation phase. Lamotrigine was titrated to a target dosage of 200 mg/d (range, 100-400 mg/d). The target dosage was adjusted as appropriate for patients receiving particular concomitant medications. Patients were given standard titration packs providing 25 mg/d of lamotrigine for the first 2 weeks, 50 mg/d for weeks 3 and 4, and 100 mg/d for week 5. Patients taking valproate and those taking carbamazepine, phenytoin, primidone, or phenobarbital were given special titration packs with those dosages halved and doubled, respectively. The investigator could lower the rate of titration or the dosage of lamotrigine during the 5-week titration period if a patient had difficulty tolerating the titration as scheduled. Although investigators were not permitted to add new medications or increase the dosages of concomitant medications to treat mood symptoms, they could reduce the dosages of concomitant medications to control side effects. Patients who in the investigator's judgment required an additional intervention to control mood symptoms were withdrawn from the study.
Subject visits were scheduled at screening/baseline, at the end of dosage titration (5 weeks), and at study end (12 weeks). Subjects were encouraged to contact the investigator more frequently if needed, and the investigator was able to contact the patient as clinically necessary. An interactive voice response system (IVRS) was used to assess quality of life and patient satisfaction with lamotrigine. Patients were instructed in the use of the IVRS during the baseline visit.
Measures and Statistics
Concurrent medications were recorded at baseline, week 5, and week 12. At these visits the investigators also assessed the patients' clinical response using the Clinical Global Impression-Bipolar Version (CGI-BPI) scale, adapted for this study. Patients used the IVRS to complete the self-rated Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) at baseline and at the week-12 visit. Q-LES-Q-SF scores were assessed as percentage of the maximum possible score, ie, (total score - minimum score)/(maximum score - minimum score), with at least 5 of the 14 items non-missing. Height was measured at baseline. Weight (kg) was recorded at baseline, week 5, and week 12. Patients rated their satisfaction with their current treatment regimen at baseline and their satisfaction with lamotrigine as a treatment for their bipolar disorder at week 12. Patient satisfaction was rated on a Likert-type scale of 1 (very dissatisfied) to 7 (very satisfied), and the percentage of patients with a score of 6 (satisfied) or 7 (very satisfied) was summarized.
Body mass index (BMI, kg/m2) was calculated, and weight and BMI were summarized, for baseline and week 12. CGI-BP overall severity scores and Q-LES-Q-SF scores at baseline and week 12 were summarized from both observed data and last observation carried forward (LOCF) data. Because results were comparable, only the LOCF data are reported here. Patients who rated their satisfaction with lamotrigine with a score of 6 (satisfied) or 7 (very satisfied) were considered to be satisfied with their medication. The percentage of patients satisfied with their medication was summarized for the total subject sample and for each group of subjects.
Safety data on weight and BMI were summarized for all patients who received at least 1 dose of study medication (ie, the safety population). Clinical response data based on CGI-BP severity and Q-LES-Q-SF scores were summarized for all patients who received at least 1 dose of study medication and provided at least 1 assessment of clinical response during treatment; these patients constituted the intention-to-treat (ITT) population. Both safety and clinical response data were analyzed with paired t tests for comparisons of changes from baseline within groups and analysis of covariance controlling for baseline value, baseline CGI-BP overall severity score, age, sex, and region for comparisons between groups.
Cite this: Effectiveness and Weight Effects of Open-Label Lamotrigine With and Without Concomitant Psychotropic Medications in Patients With Bipolar I Disorder - Medscape - May 22, 2007.