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

76 O. Elhaj and J. R. CalabreseThis study suggests that lamotrigine monotherapy is superior to both gabapentinand placebo treatments in patients with refractory affective disorders. Althoughcross-over designs have the potential for producing carry-over and other confoundingeffects, this did not seem to occur in this study, according to the authors,nor did it affect the interpretation of the outcome data based on a variety ofconsiderations. These data suggest that the response rates in this study were notconfounded by the treatment phase, nor were they influenced by carry-over effectson the severity of illness. Nonetheless, the 6-week treatment phases and total studyperiod of 18 weeks is a short period in which to assess the efficacy or persistence ofresponse. A very high percentage (92%) of this bipolar sample was rapid cycling,which is substantially greater than the general population estimates of this coursespecifier (DSM-IV). Both refractory unipolar and bipolar patients were includedin this preliminary study. In addition, the direct application of these preliminarymonotherapy results to community treatment guidelines is limited, given that acombination treatment is the norm and monotherapy regimens are rarely used inclinical practice. In contrast to the weight gain observed during treatment withgabapentin, patients lost weight while receiving lamotrigine therapy during this6-week trial, further increasing the possibility of a better side-effects profile onweight than other mood stabilizers such as lithium or valproate. However, anddespite this study’s controlled condition and vigorous data analysis, its applicabilityto the larger population of patients with bipolar disorder, especially withthe rapid-cycling course, remains limited. It is worth noting that the cross-overdesign, taking into consideration the rapidly changing nature of the rapid-cyclingcourse, might interfere with our ability to draw solid conclusions (Maj, 2001).Additionally, there was no clear differentiation between previous treatments’ineffectiveness and patient intolerance thereof.Walden et al. (2000) reported an open longitudinal investigation, where 14patients with rapid-cycling bipolar disorder were treated for 1 year with eitherlithium or lamotrigine as a mood stabilizer. Out of the seven patients withlithium, three out of seven (43%) had fewer than four and four out of seven(57%) had four or more episodes. In the lamotrigine group, six out of seven(86%) had fewer than four, and one out of seven (14%) had more than fouraffective episodes (depressive,manic,hypomanic,ormixed).Infact,threeoutofseven (43%) of the patients who were on lamotrigine therapy were without anyfurther affective episodes. There was no evidence of a preferential antidepressantversus antimanic efficacy. Although the study is limited by the small number ofpatients, the results are in line with other investigations, suggesting efficacy forlamotrigine and a suboptimal response for lithium in rapid-cycling bipolardisorder. These preliminary data need to be confirmed with controlled doubleblindstudies.