Fifteen patients (aged 18-65 years) with major depression, atypical subtype, who had been off of psychotropic medication for 7-30 days, were randomly assigned to receive, in double-blind fashion, in a 2:1 ratio, chromium picolinate (n = 10) or placebo (n = 5) for eight weeks. The dose was 400 mcg/day for the first two weeks, then 600 mcg/day, of elemental chromium (the dose was clarified in personal correspondence, Connor KM, 3/19/03). A response to treatment was defined as a decrease of at least 66% on a modified version of the Hamilton Depression Scale (HAM-D), along with a marked improvement in the Clinical Global Impressions of Improvement Scale (CGI-I; i.e., a score of 1). Remission was defined as a final HAM-D score of less than 8. The response rates were 70% (7 of 10) in the chromium group and 0% (0 of 5) in the placebo group (p = 0.02). The remission rates were 60% in the chromium group and 0% (0 of 5) in the placebo group (p = 0.04). Compared with baseline, the mean HAM-D score decreased (improved) by 59% in the chromium group and by 36% in the placebo group (p = 0.11 for difference between groups).

Comment: Atypical depression constitutes more than 20% of all cases of depression in a typical clinic population. It is characterized by mood reactivity, increased appetite and weight gain, excessive sleepiness, leaden paralysis, and sensitivity to interpersonal rejection. Atypical depression is associated with greater chronicity and disability and more suicidal ideation than are other forms of depression. Conventional treatment consists primarily of monoamine oxidase inhibitors. Although it is a more serious condition than dysthymia (described above), atypical depression is similar to it in some ways, and might therefore conceivably be related to blood-glucose dysregulation. The beneficial effect of chromium picolinate in the treatment of atypical depression may be related to its ability to improve glucose metabolism. Another study has shown that chromium picolinate supplementation causes postsynaptic downregulation of 5HT2A (serotonergic) receptors, an effect which might also account for its antidepressant activity.

Davidson JRT, et al. Effectiveness of chromium in atypical depression: a placebo-controlled trial. Biol Psychiatry 2003;53:261-264.