Impact of suppression of thyroxine on folate status during acute antidepressant therapy

Antidepressant response is associated with a rise in red cell folate (RCF) and a reduction in thyroxine (T4). Since T4 levels may directly influence folate status, it is possible that the increase in folate with recovery results from the decline in T4. To examine the possible role of thyroid hormones in the observed change in folate status during antidepressant therapy, T4, tri-iodothyronine (T3) or placebo was given in a double-blind fashion to 25 depressed subjects at the initiation of standard antidepressant treatment. Folate levels and mood [using the Hamilton Rating Scale for Depression (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI)] were measured at baseline and following 4 weeks of therapy. Using MANOVA for repeated measures, there was a significant interaction between response status and time for vitamin and hormone levels. Univariate analysis confirmed that response was associated with a significant change in red cell folate, but not a significant change in T4 or T3. The mean change in RCF across the 4-week trial was significantly greater in the 14 responders than the 11 non-responders. Change in RCF, and not change in T4 or T3, was significantly correlated with change in HAMD and contributed significantly to the variance in change in HAMD. These results suggest that change in RCF is closely tied to response to antidepressant treatment, and this effect is not inhibited by exogenous administration of thyroid hormones or the changes in T4 that the exogenous hormones produce. These findings support the possible role of folate, independent of thyroid function, in the modulation of mood.