Supraphysiological doses of L-thyroxine in the maintenance treatment of prophylaxis-resistant affective disorders.

This prospective open-label study examined the efficacy of adjunctive supraphysiological doses of L-thyroxine (T(4)) in the maintenance treatment of prophylaxis-resistant affective disorder. Twenty-one (16 women, 5 men) of 25 patients enrolled consecutively over an 8-year period on the basis of their status of prophylaxis resistance (defined as two or more failures to standard prophylactic trials) participated for more than four months in the study and were eligible for the intention-to-treat analysis. The mean length of adjunctive treatment with T(4) was 51.4 +/- 21.7 months. The mean T(4) dose at study end was 378.6 +/- 90.2 micro g/d. The number of episodes and hospitalizations, and the morbidity indices during the time of prophylactic T(4) treatment, were compared with those measured for the same length of time before the start of T(4) treatment (mirror-image method). On the Clinical Global Impression for Bipolar Disorder scale (CGI-BP, Change from Worst Phase of Illness), eleven subjects (52.4%) were rated as "very much improved", four (19%) as "much improved", two (9.5%) as "minimally improved" and four (19%) as "no change." The mean total number of recurrences (8.6 before T(4) treatment vs. 2.8 during T(4) treatment; p =.004), the number of hospitalizations (3.1 vs. 1.9; p =.026) and the Morbidity Index (MI(Total) = 0.71 vs. MI(Total) = 0.28; p <.001) significantly declined during T(4) treatment. Subjects with bipolar disorder (n = 13) benefited more from the T4 treatment intervention than did subjects with unipolar major depressive disorder (n = 4) and schizoaffective disorder (n = 4). In conclusion, adjunctive treatment with L-thyroxine in supraphysiological doses may be an effective strategy in the maintenance treatment of patients with prophylaxis-resistant affective disorders.