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

340 J. Cookson and S. GhalibTable 15.4 Prediction of response to antidepressant drug in modelsModelPrediction1. Mixture of elements (mood,activity, thinking)Partial response (in depressive elements)2. Severe stage of mania No response3. Dysphoric mania No prediction4. Depression as characterologicalresponse to maniaNo response5. Manic defense in depression Improved6. Transition state during a cycle(MDI/DMI)7. Predominantly depressed (BP-II,Dm)8. Mania modified by substancemisuseDMI: shortened depression, mania or hypomaniaoccur sooner; stabilize mood ‘‘from below’’Depression improved, mania more evidentResistance while comorbidity persists9. Modified by organic brain disease Resistance while comorbidity persistsSee text for definition of abbrevations.Similarly, Koukopoulos et al. (1992) reported 45 patients with bipolar disorderwho experienced a mixed depressive syndrome, meeting DSM-IIIR criteriafor major depression but not for mania, who deteriorated when treated withantidepressants, displaying increased agitation, insomnia, and, in some cases,suicidal impulses. The continuation of antidepressants may eventually resultin rapid cycling (Koukopoulos et al., 1983). On the other hand, a substantialproportion of depressed patients with mild bipolar features may show satisfactoryand stable long-term outcome with antidepressants not necessarily combinedwith mood stabilizers (Cassano, 2002).Monoamine oxidase inhibitors may be effective in bipolar depressed states.Himmelhoch et al., (1991) conducted a double-blind randomized study comparingimipramine (100–300 mg/day) with the stimulant monoamine oxidaseinhibitor tranylcypromine (20–60 mg/day) in 56 outpatients with anergic bipolardepression. Tranylcypromine was superior to imipramine with greater symptomaticimprovement and a higher global response rate, with no greater risk oftreatment-induced hypomania or mania (14% and 20%). The 12 non-respondersto imipramine were then crossed over to tranylcypromine and nine responded(Thase et al., 1992).It is unclear whether mixed states are more or less likely to deteriorate thanpure manias when exposed to antidepressants. For example, in a study by Altshuleret al. (1995) of 51 patients with BP-I and BP-II, 85% switched to mania while