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

71 Rapid-cycling bipolar disorderLamotrigineLamotrigine utilization as a first option in the treatment of rapid-cycling bipolardisorder has gained more consensus (Sachs et al., 2000b; American PsychiatricAssociation, 2002).Calabrese et al.(2000b) reported on the first multicenter, double-blind, flexibledose,placebo-controlled, parallel-group study to examine the safety and efficacyof lamotrigine for the long-term prophylaxis of mood episodes in patients withrapid-cycling bipolar disorder.A total of 324 patients meeting DSM-IV criteria for rapid-cycling disorder enteredthe open-label phase, and 182 patients were eventually randomly assigned to thedouble-blind maintenance phase. For patients entering the open stabilization phase,the mean age was 38 years, the percentage of women was 59%, the percentage ofBP-I subtype was 69%, and the percentage of patients receiving thyroid supplementsfor diagnosed hypothyroidism was 7%. At study entry, 57% of patients weredepressed, 20% were hypomanic or manic, 18% were euthymic, and 5% had mixedstates. The mean number of mood episodes in the 12 months prior to study entry was6.3. The lifetime prevalence of psychosis was 27%, and the percentage of patients withprior suicide attempts was 36%. Prior lifetime exposure to psychotropics includedlithium (68%), carbamazepine (27%), divalproex (57%), lamotrigine (< 1%), antidepressants(82%), and antipsychotics (27%). Concomitant psychiatric medicationsat study entry included lithium (19%), carbamazepine (4%), divalproex (19%),antidepressants (30%), and antipsychotics (7%). Although the most commonlyprescribed lifetime medications at the time of study entry were antidepressants, only36% of patients reported having responded to them positively.Lamotrigine was added to the patients’ current psychotropic regimens andtitrated to clinical effect during an open-label treatment phase. The treatment ofstabilized patients with other psychotropics was tapered off and randomlyassigned to lamotrigine or placebo monotherapy (in a 1:1 ratio) for 6 monthsafter being stratified for BP-I or BP-II disorder.Lamotrigine dose was titrated in the 6-week preliminary phase to a target doseof 200 mg/day. After week 5, lamotrigine dose increases were allowed in incrementsof 100 mg/week up to a maximum dose of 300 mg/day. In the randomizedphase, the double-blind medication dosage was also flexible and varied from 100 to500 mg/day. The average daily dose was 288 94 mg.Time to additional pharmacotherapy for emerging symptoms of a mood episodewas the primary outcome measure. Secondary outcome measures includedsurvival in the study, percentage of patients stable without relapse for 6 months,and changes in scores on the Global Assessment Scale (GAS) and the CGI-Severityof Illness (CGI-S) scale.