Of the 1175 patients who received at least 1 dose of study medication, 1139 provided at least 1 clinical assessment during treatment. Table 1 summarizes the demographic characteristics of the safety population as well as concomitant psychiatric medication use and patient disposition. The age of patients (mean ± SD) was 42.2 ± 13.1 years, and 96.5% were older than 18 years. The majority of patients were female (64%) and of white ethnicity (90%).
At the start of lamotrigine therapy, patients were taking a mean of 2.38 ± 1.45 prescription psychotropic medications. Of the 1175 patients constituting the safety population, 20% were being treated with lamotrigine monotherapy and 80% were receiving adjunctive lamotrigine (ie, lamotrigine in addition to 1 or more psychotropic drugs, including but not limited to valproate, lithium, antipsychotics, and antidepressants). Patients receiving therapy concomitant with lamotrigine consisted of 778 patients (66%) treated with antidepressants, 352 (30%) taking antipsychotics, 267 (23%) receiving lithium, and 260 (22%) taking valproate. The mean doses of lamotrigine ± SD for completers at week 12 were: 101.1 ± 30.43 for the 179 patients receiving valproate; 191.4 ± 57.51 for the 686 patients who were not taking concomitant valproate; 304.3 ± 108.7 for the 41 patients receiving carbamazepine, phenytoin, primidone, or phenobarbital; 184.1 ± 43.93 for the 646 patients not receiving valproate or carbamazepine (or phenytoin, primidone, or phenobarbital); 174.0 ± 59.98 for the 207 receiving lithium; and 165.3 ± 69.73 for the 659 patients not receiving lithium. Eight hundred sixty-seven patients (74%) completed the study ( Table 1 ). The most common reasons for early withdrawal were adverse events, being lost to follow-up, and voluntary withdrawal (ie, patient's decision).
On average, patients in the ITT population were mildly to moderately ill at baseline, with a mean CGI-BP overall severity score of 3.4 ± 1.32, and were minimally to mildly ill after 12 weeks of open-label treatment with lamotrigine, with a mean score of 2.4 ± 1.22 (P < .0001 for change from baseline).
Statistically significant improvement from baseline in CGI-BP overall severity mean scores was observed at week 12 in patients receiving lamotrigine monotherapy and adjunctive lamotrigine as well as in those patients taking lamotrigine with and without concomitant valproate, lithium, antipsychotics, or antidepressants ( Table 2 ). Improvement from baseline was similar in patients taking lamotrigine monotherapy vs adjunctive lamotrigine (adjusted mean difference, 0.08; 95% confidence interval [CI], -0.08 to 0.24; P = .3336). There were no significant differences in clinical improvement between patients taking lamotrigine with vs without valproate (adjusted mean difference, -0.11; 95% CI, -0.26 to 0.05; P = .1764), lithium (adjusted mean difference, 0.08; 95% CI, -0.08 to 0.23; P = .3386), antipsychotics (adjusted mean difference, -0.10; 95% CI, -0.24 to 0.04; P = .1657), or antidepressants (adjusted mean difference, -0.02; 95% CI, -0.16 to 0.12; P = .7574).
Quality of Life
In the ITT sample, the Q-LES-Q mean score as a percentage of the maximum possible score increased from 50.6 ± 18.30 at baseline to 60.9 ± 19.48 after 12 weeks of lamotrigine treatment, with a mean increase of 10.1 ± 20.07 points (P < .0001). As shown in Table 3 , quality-of-life mean scores improved significantly during open-label lamotrigine monotherapy or adjunctive therapy (P < .0001). Patients receiving lamotrigine with and without valproate (P < .0001), lithium (P < .0001), antipsychotics (P < .0001), and antidepressants (P < .0001) also showed significant improvement in quality-of-life scores. There were no significant differences in change in Q-LES-Q mean score as percentage of the maximum possible score between patients receiving lamotrigine monotherapy and those taking adjunctive lamotrigine (adjusted mean difference, -1.52; 95% CI, -4.41 to 1.38; P = .3039) or between patients receiving lamotrigine with and without valproate (adjusted mean difference, 0.88; 95% CI, -1.94 to 3.70; P = .5399), lithium (adjusted mean difference, 0.44; 95% CI, -2.29 to 3.16; P = .7531), or antidepressants (adjusted mean difference, 0.50; 95% CI, -2.00 to 2.99; P = .6958). However, patients without concomitant antipsychotics experienced greater improvement in quality-of-life scores than those with concomitant antipsychotics (12.7 vs 9.1), with a statistically significant adjusted mean difference of 3.62 (95% CI, 1.16 to 6.08; P = .0040).
Weight and BMI
In the safety population (N = 1175), lamotrigine treatment was not associated with significant changes in mean weight from baseline (188.1 ± 48.21 lb) to week 12 (188.9 ± 48.41 lb) ( Table 4 ). The mean weight at baseline was significantly higher for patients taking valproate than for those not taking valproate (difference, -14.2 ± 47.77 lb; P < .0001) and in patients taking antipsychotics vs patients not taking antipsychotics (difference, -6.6 ± 48.04 lb; P < .05). However, in all groups, there were no additional changes in weight at week 12 of open-label lamotrigine treatment, and there were no differences in weight change between groups (lamotrigine monotherapy vs adjunctive lamotrigine: adjusted mean difference, -0.58; 95% CI, -1.97 to 0.78; P = .4031; valproate vs no valproate: adjusted mean difference, 0.12; 95% CI, -1.19 to 1.44; P = .8567; lithium vs no lithium: adjusted mean difference, -0.24; 95% CI, -1.49 to 1.02; P = .7106; antipsychotics vs no antipsychotics: adjusted mean difference, 0.36; 95% CI, -0.80 to 1.52; P = .5450; antidepressants vs no antidepressants: adjusted mean difference, -0.19; 95% CI, -1.35 to 0.97; P = .7487). When patients were stratified according to obesity status at baseline, no statistically significant changes in weight were observed at week 12 in nonobese patients (BMI < 30) from the safety population. Furthermore, no statistically significant weight change occurred in nonobese patients taking lamotrigine as monotherapy or adjunctive therapy, or taking lamotrigine with or without concomitant valproate, lithium, antipsychotics, or antidepressants. While no statistically significant change in weight was observed in obese patients from the safety population, obese patients treated with adjunctive lamotrigine, but not those receiving lamotrigine monotherapy, experienced modest but statistically significant weight loss at week 12 relative to baseline (-2.20 ± 19.33 lb, P = .04). No statistically significant changes in weight were observed in obese patients taking open-label lamotrigine with or without valproate, lithium, or antipsychotics or in those taking lamotrigine without antidepressants. However, in obese patients taking concomitant antidepressants, open-label lamotrigine was associated with a statistically significant decrease in weight at week 12 (mean change -1.10 ± 8.75 lb, P < .05).
Similar results were observed for BMI. The mean BMI of the overall sample was 30.1 ± 7.23 kg/m2 at baseline and did not change significantly after 12 weeks of lamotrigine treatment (0.0 ± 1.34 kg/m2). BMI was not significantly altered in patients receiving lamotrigine monotherapy and adjunctive therapy or in patients taking lamotrigine with and without valproate, lithium, antipsychotics, or antidepressants ( Table 5 ). There were no significant differences in change from baseline to week-12 BMI between groups (lamotrigine monotherapy vs adjunctive lamotrigine: adjusted mean difference, -0.08; 95% CI, -0.30 to 0.14; P = .4990; valproate vs no valproate: 0.01; 95% CI, -0.21 to 0.22; P = .9527; lithium vs no lithium: -0.05; 95% CI, -0.25 to 0.16; P = .6654; antipsychotics vs no antipsychotics: adjusted mean difference 0.04; 95% CI, -0.15 to 0.24; P = .6513; antidepressants vs no antidepressants: -0.06; 95% CI, -0.25 to 0.13; P = .5565).
The percentage of patients who were satisfied with their treatment improved from 34% with current treatment at baseline to 58% after 12 weeks of lamotrigine treatment (Figure)
The percentage of patients who were satisfied with lamotrigine therapy was similar for patients receiving lamotrigine monotherapy (54%) and adjunctive lamotrigine (60%). Patient satisfaction was also similar in patients receiving lamotrigine with (60%) and without (58%) concomitant valproate, with (60%) and without (58%) concomitant antipsychotics, with (64%) and without (60%) concomitant lithium, and with (59%) and without (56%) concomitant antidepressants.
Adverse events were reported in 692 patients (59%) overall and were deemed to be drug-related in 452 (38%). Detailed information about adverse events in the overall study population is reported elsewhere. Adverse events thought to be drug-related and reported in 5% or more of any of the patient groups in this analysis were headache, rash, dizziness, and tremor ( Table 6 ). Serious adverse events were reported in 41 patients (3%) and were primarily psychiatric; only 1, a report of mania, was considered to be related to lamotrigine treatment.
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.