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

335 The treatment of bipolar mixed statesTable 15.3 Prediction of response to antimanic drug in modelsModelPrediction1. Mixture of elements (mood,activity, thinking)Partial response (in manic elements)2. Severe stage of mania Proportionately large response3. Dysphoric mania Different from response in pure mania4. Depression as characterologicalresponse to maniaDepression improves as mania improves5. Manic defense in depression Depression worsened6. Transition state during a cycle(MDI/DMI)7. Predominantly depressed(BP-II, Dm)8. Mania modified by substancemisuseMDI: shortened mania; less severe depression;stabilize mood ‘‘from above ’’Depression persists or worsensResistance while comorbidity persists9. Modified by organic brain disease Resistance while comorbidity persistsSee text for definition of abbrevations.The relatively short duration of studies in acute mania (3–4 weeks) means thatlonger-term outcomes, and in particular the switch into depression, may not beexplored in the duration of the trial.Discontinuation of lithium over a period of less than 2 weeks can increase thelikelihood of mania developing or worsening. Abrupt discontinuation can lead tothe development of mania in as many as 50% of bipolar patients who have beenstabilized on the drug (Mander and Loudon, 1988; see Cookson, 1997 ). Little isknown of how the discontinuation of other drugs may affect the clinical pictureand response to treatment.Treatment responses in different models of mixed statesThe different concepts or ‘‘models’’ of the nature of mixed states lead to differentpredictions as to how drugs are likely to affect the condition. The predictions withrespect to treatment with a drug that has antimanic but not antidepressantproperties are shown in Table 15.3.In general, with the exception of model 2 (severe stage), the models predict thatmixed states will respond less fully to antimanic drugs, such as antipsychotics.There is limited evidence that dysphoric mania (model 3) responds differently,and that in severe mania there is a proportionately greater response (model 1).Thus, in a double-blind placebo-controlled cross-over study of carbamazepine in