Bipolar Disorders: Mixed States, Rapid-Cycling, and Atypical Forms

75 Rapid-cycling bipolar disorderCochran’s Q-statistic was used to compare the overall CGI response (i.e.,considered a rating of either much or very much improved) for those patientswho completed all three phases. Any significant Cochran’s Q statistic was followedby a post hoc test. This test allowed pairwise comparisons of the proportion ofresponders in the medication phases to determine the location of a difference. TheFisher exact test was used for differential response rates based on gender status.Clinical responseThe mean daily doses at week 6 were 274 128 mg for lamotrigineand 3987 856 mg for gabapentin. There was no difference in lamotrigine andgabapentin doses between responders and non-responders. The response rates basedon the overall CGI rating of much or very much improved were the following:lamotrigine, 52% (16 / 31); gabapentin, 26% (8 / 31), and placebo, 23% (7 / 31).Post hoc Q differences (df ¼ 1, n ¼ 31) were the following: lamotrigine versusgabapentin (Q diff ¼ 5.33, P ¼ 0.011), lamotrigine versus placebo (Q diff ¼ 4.76,P ¼ 0.022), and gabapentin versus placebo (Q diff ¼ 0.08, P ¼ 0.700). The CGIresponse rates for manic and depressive components of the illness separatelywere similar to the overall response rate, but they only achieved trend levels ofsignificance. The response rates for mania were the following: lamotrigine, 44%(11 / 25); gabapentin, 20% (5 / 25); and placebo, 32% (8 / 25). For depression, theresponse rates were the following: lamotrigine, 45% (14 / 31); gabapentin, 26%(8 / 31); and placebo, 19% (6 / 31). The response rate observed during phase I washighly similar to that in the whole study using all three phases of the cross-overtrial; it was 50% (5 / 10) for lamotrigine, 33% (3 / 9) for gabapentin, and 18% (2 /11) for placebo. In addition, when the response data were analyzed as a function ofa positive response in the preceding phase, only 23% of lamotrigine responders,50% of gabapentin responders, and 0% of placebo responders were also partialresponders in the previous phase, and would thus have entered the next phasesomewhat improved. This finding further indicates that there was not a greaterpercentage of lamotrigine-responsive patients who were responders in the precedingphase. Moreover, there were no significant differences at the baseline level onany of the supplementary ratings of severity of illness. There was no differencebetween the response rates based on gender. Both agents were generally welltolerated, with the exception of one patient, who was administered lamotrigineand who developed a rash after the 6-week study phase was over. The rashoccurred in week 15 (during the continuation treatment), progressed to toxicepidermal necrolysis, and required the patient to be hospitalized in an intensivecare burn unit. The patient recovered fully. A pairwise contrast (lamotrigine versusgabapentin, F ¼ 5.884, P ¼ 0.021) showed that patients lost weight when theyreceived lamotrigine relative to the weight gained when they received gabapentin.