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

339 The treatment of bipolar mixed statesresponded, a 25% advantage for clozapine, corresponding to a ‘‘number needed totreat’’ of four.Long-term studies of olanzapine are discussed in Chapter 16, and suggest thatthis atypical antipsychotic and antimanic drug may reduce not only manic but alsoa proportion of depressive recurrences.LamotrigineResults from an open-label study of lamotrigine for treatment of BP-I disordersuggested that lamotrigine was effective in the treatment of depressive and manicsymptoms (Calabrese et al., 1999a). Subsequently, a 7-week double-blind, placebocontrolledstudy demonstrated that lamotrigine monotherapy was effective fordepressive episodes in 159 patients with BP-I disorder as early as 3 weeks afterinitiating therapy (Calabrese et al., 1999b). More recently, the efficacy and tolerabilityof lamotrigine monotherapy for BP-I disorder were established in two18-month placebo-controlled maintenance studies (Bowden et al., 2002; Calabreseet al., 2002) and a meta-analysis of these two trials, where lamotrigine was foundto reduce significantly mean Hamilton-D and Clinical Global Impression (70)scores across 76 weeks of treatment in 638 patients (Goodwin et al., 2002). Theseresults suggest that lamotrigine is effective for the acute treatment and long-termmanagement of BP-I depression. Acute effectiveness has also been demonstrated inpatients with treatment-refractory (Bowden et al., 2000) andrapid-cyclingBP-IIdisorder (Bowden et al., 2001), as well as a cohort of recently manic patients withBP-I disorder (Frye et al., 2000). It would appear important to examine furtherwhether these responses were related to the patterns of mood cycles in the patients,using the classifications of Angst and of Koukopoulos.Treatment of mixed states with antidepressantsThe predictions of responses to antidepressants in different models of mixed statesare shown in Table 15.4Antidepressants in bipolar mixed statesThe use of antidepressants in bipolar depression is controversial, because of thesuspected risk of triggering mania; their use in mixed states is also controversial.Akiskal and Mallya (1987) described 25 patients referred for treatment-resistantdepression who displayed subacute or chronic mixed states apparently induced bytricyclic antidepressants. They improved with discontinuation of antidepressantsand treatment with lithium or carbamazepine, with or without antipsychotics.Akiskal (2002) has argued that failure to recognize such a depressive mixed state asbeing bipolar is a serious clinical lapse, as antidepressants are likely to aggravate it.