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The common pattern of cortical glucose metabolism increases and limbic-paralimbic metabolism decreases in placebo and fluoxetine responders suggests that facilitation of these changes may be necessary for depression remission, regardless of treatment modality. Clinical improvement in the group receiving placebo as part of an inpatient study is consistent with the well-recognized effect that altering the therapeutic environment may significantly contribute to reducing clinical symptoms. The additional subcortical and limbic metabolism decreases seen uniquely in fluoxetine responders may convey additional advantage in maintaining long-term clinical response and in relapse prevention.

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An aim in development of new antidepressants (ADs) now includes increasing speed of action. New drugs are tested primarily in outpatients who are less severely depressed than the patients treated in earlier trials of the tricyclic drugs. To determine early efficacy requires measures sensitive to initial changes in components of the illness as well as in the severity of the entire syndrome of depression. This paper describes the development of a brief 'multivantaged' (MV) method for assessing the major behavioural and affective components of depression. The revised Brief MV was significantly reduced from the original to make it more feasible to apply in outpatient studies. In this study we determined the Brief MV's (1) reliability and comparability to the original and (2) its ability to detect the onset of specific behavioural effects in outpatients treated with paroxetine for 6 wk. The latter is compared to the ability of the Hamilton Depression Scale (HAMD) to detect changes in global severity. The constructs derived from the Brief MV were found to be highly similar to those of the original version and as reliable. In depressed patients who responded to paroxetine, the HAMD and MV detected onset of improvement after 7 d of treatment. The Brief MV revealed that the improvement in global severity was due to the drug's action at this time on behaviours such as anxiety and distressed expression, as well as on a severity dimension of anxiety-agitation-somatization. Thus, the Brief MV, in uncovering underlying behavioural actions, represents an important addition to the current unidimensional HAMD approach in drug research.

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