Clinical selectivity of antidepressants with pharmacological specificity still remains under debate.

In the open trial presented below, the effects of fluoxetine, a selective serotonin re-uptake inhibitor (SSRI), were compared across two groups of depressive inpatients contrasted on their symptomatological expression (agitated/anxious versus retarded/blunted affect). Sixteen patients (8 in each groups) were included in the 4-weeks treatment period and submitted to a weekly-based evaluation. Global depression, retardation, emotional blunting, agitation, anxiety and mood profile were assessed.

Significant improvements of the HDRS and MADRS scores were observed in both groups. Although no group x treatment interaction was found on the global scores of depression, a differential effect according to the group was observed on anxiety, agitation, irritability and emotional lability.

These preliminary results support the hypothesis that the effect of fluoxetine on positive clinical dimensions could lead to a differential effect in patients with agitation/anxiety when compared with patients with retardation/blunted affect.

A prominent theory of depression focusses on neural plasticity and stress as central issues in seeking to develop a pattern of identifiable biological markers for the depressive disorders. Relative neglect, however, of clinical factors in that theory limits the uncovering of markers and opens to question their methodological approach. A conflicting theory, the ‘opposed neurobehavioral states’, based on dimensional analysis of monoamine neurotransmitter systems and behavioural factors is presented. This perspectives paper contrasts the two approaches viewing the biomarkers theory as premature at this point in the progress of depression research.

Studies developed to support the biomarkers theory and the opposed neurobehavioral states theory are examined for their strengths and limitations in explaining the nature of the disorder and the actions of therapeutic drugs. Reference is made to reviews of the many studies on biomarkers and the recent work that supports the opposed neurobehavioral states theory.

Main issue: the biomarkers theory sets important goals, but despite the many advances in the neural investigations of factors underlying depression, is still not successful in specifying markers. Thus, it is believed to be applying the wrong methodologic approach and premature in its claims. Perspective: the ‘opposed neurobehavioral’ theory is limited in its breadth of research. It applies, however, the dimensional approach to the clinical side of the problem, a methodological approach more likely to be effective in selecting the best clinical treatment and open to a more productive path to understanding of the nature of the disorder in future research.