We previously demonstrated that the difference between 23.00h and 08.00h TSH response to TRH tests on the same day (ΔΔTSH test) is reduced in about 75% of drug-free depressed inpatients. This study sought to determine whether this chronobiological index, at baseline and after 2 weeks of treatment, could predict antidepressant response.

The ΔΔTSH test was performed in 50 drug-free DSM-IV euthyroid major depressed inpatients and 50 hospitalized controls. After 2 weeks of antidepressant treatment the ΔΔTSH test was repeated in all inpatients. Antidepressant response was evaluated after 6 weeks of treatment.

At baseline, ΔΔTSH values were significantly lower in patients compared to controls (p< 0.000001): 38 patients showed reduced values (i.e. ΔΔTSH ≤ 2.5 mIU/L; sensitivity, 76%; specificity, 98%). After two weeks of treatment, 20 patients showed ΔΔTSH normalization (among them 18 were subsequent remitters), while 18 patients did not normalize their ΔΔTSH (among them 15 were non remitters) (p < 0.00001). Among the 12 patients who had normal ΔΔTSH values at baseline, 8 out 9 who had still normal values after 2 weeks of treatment were remitters, while the 3 with worsening thyroid axis function (i.e. reduced ΔΔTSH value after 2 weeks of treatment) were non-remitters (p< 0.02).

Our results suggest that after 2 weeks of antidepressant treatment: 1) an abnormal ΔΔTSH test could predict non-remission, and 2) ΔΔTSH normalization is associated with subsequent remission. Thus, chronobiological restoration of the thyroid axis activity precedes clinical improvement and may predict the therapeutic outcome in major depression.