Selective serotonin reuptake inhibitor efficacy in severe and melancholic depression

Depression with melancholic features appears to be a discrete affective syndrome characterised by profound psychomotor, cognitive and mood disturbances that are qualitatively different from other forms of depression. Some investigators have hypothesised that melancholia may have a neurological basis with psychomotor disturbances associated with selective alterations in dopamine neurotransmission and disturbances in basal ganglia function. A number of studies have examined the role of selective serotonin reuptake inhibitors (SSRIs) in the treatment of melancholia. Although relatively few prospective trials have focused on melancholic depression, several retrospective meta-analyses and trials in populations that are likely to include a high proportion of melancholic patients have provided a wealth of data. While some early studies suggested that SSRIs might be less effective in the treatment of melancholia, the results of these may have been biased and confounded by several side-effects of tricyclic antidepressants (TCAs), which might contribute to their apparent efficacy. It appears, however, that the SSRIs may vary among themselves in their apparent efficacy in melancholia. In this regard, sertraline may be more efficacious than other SSRIs and similar to TCAs in the treatment of patients with melancholia. Several studies have suggested that the presence of melancholic features may predict a good response to sertraline, and it has been hypothesised that this may be the result of the relatively potent dopaminergic activity of sertraline, compared with other SSRIs.