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

100 E. Vieta et al.1998), which deserves replication. Data on the comparative efficacy of valproateare scant.With a sample of rapid-cycling bipolar patients, Calabrese et al. (2000) studiedthe safety and efficacy of lamotrigine in a double-blind, placebo-controlled study.The results suggested that lamotrigine might be a well-tolerated and effectivemood stabilizer with prophylactic properties when used as monotherapy insome patients with rapid cycling. Differences favoring lamotrigine were consistentlygreater for bipolar II than bipolar I patients. An open study is also supporting theefficacy of lamotrigine in bipolar II disorder (Vieta et al., 2003), though anunpublished double-blind trial could not separate its effects from placebo in thisparticular population. Another anticonvulsant, topiramate, seemed to be moreuseful for the hypomanic phase (Vieta et al., 2002b).Regarding antidepressant treatment, its impact is positive for unipolarpatients but unclear and sometimes self-defeating for bipolar patients becauseantidepressant treatment, especially tricyclic antidepressants, implies an importantrisk of switch induction or cycle acceleration. In bipolar I patients the treatmentaims to prevent manic relapses; consequently, lithium is the primary treatmentin bipolar I patients because of its prophylactic effect on mania, and also becauseit has greater antidepressant efficacy in bipolar I depressive disorder. On theother hand, in bipolar II patients it is very important to control and preventdepressive episodes; consequently, lamotrigine and antidepressant treatment(mostly represented by the selective serotonin reuptake inhibitors), which haveless propensity for hypomania induction, may be useful (Bourgeois, 2002).In practice, the decision to use concurrent mood stabilization during the treatmentof bipolar II depression must be made on a case-by-case basis, with age atonset, cycle length, past history of rapid cycling, patient gender, and priorfrequency and severity of hypomanias important considerations (Thase andSachs, 2000).Atypical antipsychotics have also been tried in bipolar II disorder, though norandomized, double-blind trials are yet available (Crespo and Vallejo, 2002;Vieta, 2003). A cohort of bipolar II hypomanic patients was treated withadjunctive risperidone by Vieta et al. (2001a), with good results. Efficacy wasfully comparable to that found in bipolar I manic patients (Vieta et al., 2001b),thus supporting the dimensionality of the (hypo)manic spectrum. Besides,doses correlated with the intensity of symptoms, being higher for manic thanfor hypomanic patients (Vieta et al., 2001b). Other atypicals have beenreported to be useful in the treatment of patients within the bipolar spectrum,including bipolar I and II. Olanzapine (Vieta et al., 2001c) and quetiapine(Vieta et al., 2002c) may show some promise, even in the ‘‘softer’’ range ofbipolarity.