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

379 Investigational strategiescategorized as zero phase changes, because no episode lasted longer than 24 h. Thisapproach simplifies the measurement of treatment outcome and decreases thevariance attributable to individual raters by not requiring fine distinctions.STEP-BD assesses clinical states prospectively using the Clinical MonitoringForm (CMF), which also serves as the progress note in the patient’s medical record.The CMF is a one-page assessment tool (available from www.manicdepressive.org;Sachs et al., 2002a) consisting of nine parts, including modified versions of theStructured Clinical Interview for DSM-IV (SCID) current mood modules; associatedsymptoms, stressors, medical problems, and comorbid conditions; selectedmental status items; current medication compliance and adverse effects; laboratorydata; summary scores (i.e., clinical status, Clinical Global Impressions Severityof Illness and Global Assessment of Functioning) narrative, and treatment plan.The CMF’s operational conventions for concise clinical record-keeping allow itto serve as the source document as well as a key outcome measure in STEP-BD(Sachs et al., 2002b). Central to the tracking of outcome is designation of thecurrent clinical status. Course of illness over time can be determined prospectivelyby using the CMF clinical status designations made at every follow-up visit. Theeight mutually exclusive clinical states are outlined in Figure 17.5. This clinicianratedtechnique makes use of, but does not rely on, self-report measures such as theSTEP-BD waiting-room self-report form and daily mood-charting. The CMF, itscompanion waiting-room self-report form, daily mood charts, and full instructionsfor their use are available at www.manicdepressive.org. These methods donot eliminate the problems encountered in tracking treatment response in patientswith rapid cycling. Figure 17.4 depicts the disparate assessments made by raters fora rapid-cycling bipolar patient subject during the 1st and 12th month of valproicacid treatment. As noted above, using the 48-h rule and simplifying the outcomecriteria helps to avoid potential discrepant ratings.Rapid cycling: clinical trial design issuesResearch on rapid cycling need not wait until perfect solutions are found for themany daunting problems noted here. Considerable progress can be made by firsttesting simple approaches to the easiest questions.Sample selection and outcome measures are perhaps the most important aspects ofany trial. Although retrospective assessment of rapid cycling at study entry doesappear to give an indication of the propensity to cycle (Baldessarini et al., 2000),studies are disadvantaged when subjects likely to remain well are randomized.Limiting randomization to only those subjects with active cycling during a prospectiveassessment period can help reduce this problem. We recommend enteringretrospectively diagnosed subjects into a stabilization phase lasting 2–3 months