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Mania is likely to be antidepressant-induced and not attributable to the expected course of illness in one-third of treatment-refractory bipolar patients, and rapid cycling is induced in one-fourth. Antidepressant-induced mania may be a marker for increased vulnerability to antidepressant-induced cycle acceleration. Antidepressant-induced cycle acceleration (but not antidepressant-induced mania) is associated with younger age at first treatment and may be more likely to occur in women and in bipolar II patients.

This paper 1) demonstrates the ejgicacy of nimodipine in the treatment of a patient with rapid-cycling bipolar disorder using a n intensive single subject design, and 2) evaluates three statistical techniques that are usefil in the analysis of single case data. The patient is a 42-year-old bipolar II female reji-actory to multiple medication trials who underwent double-blind treatment with placebo (B), nimodipine (A), and verapamil (C) in a B-A-B-A-C-A design. The use of statistics in single subject studies has been the subject of controvery. One problem with single subject data is that data points are oj3en correlated with data points @om adjacent time periods (i.e., nonindependent), and therefore such data have been considered inappropriate f o r statistics that assume independence of error terms. One statistical technique we examined was a t-test in the context of repeated on-ofidrug trials suggested by Gentile, Roden, and Klein (1972), in which all data points @om treatment phases are aggregated and then compared to aggregated data ji-om baseline or placebo phases. We compared this t-test to a variant of meta-analysis in which each phase is statistically compared to its adjacent phases and the t-values ji-om those comparisons are summed and converted to a z-score. A s illustrated with this patient, the t-test method tended to be more conservative than the z-score method in instances where there is an overall time trend f o r improvement or deterioration. The Chassen technique also provides an alternative f o r analysis of data with time trends. The z method was more conservative than the single aggregated t-test i f t h e direction of predicted change on a given measure (i.e., improvement during a n active drug phase and deterioration during a placebo phase) did not occur as expected at each medication transition. These statistical techniques, in combination with the sequential off-on-off-on clinical trial design, provide strong evidence f o r the mood-stabilizing effect of nimodipine in this rapid-cycling BP II female. Depression 2: 259-271 (1 99411 995). 0 199y Wiley-Liss, Inc. *

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