Electroconvulsive therapy (ECT) is an important and effective antidepressant treatment. However, temporary confusion and memory impairments remain significant side effects. There are numerous interactions among ECT, homeostasis of the hypothalamic-pituitary- thyroid axis, depressive symptomatology, and neurocognitive functioning. The findings of previous pre-clinical and clinical investigations led to the principal investigator to conduct a double-blind, placebo- controlled, pilot study of combined ECT and thyroid hormone treatment in a series of 20 male inpatients. Result indicated that a nightly dose of 50 micro g of triiodothyronine (T3) significantly accelerated the antidepressant action of ECT, diminished the amnestic sequelae, and increased seizure durations. The proposed investigation will expand on the preliminary work to include a larger, more representative group of patients, and test the study hypotheses with a more rigorous research design. Four major hypotheses will be tested: 1) The adjunctive administration of T3 during the course of ECT will enhance the clinical efficacy of ECT. Specifically, it is expected that patients receiving T3 plus ECT will be more likely to achieve an adequate antidepressant response and have an accelerated antidepressant response, compared to patients receiving ECT and placebo. 2) The combined treatment will diminish the neurocognitive side effects associated with ECT. Specifically, it is expected that patients receiving T3 plus ECT will have less disorientation and attentional deficits following individual ECT treatments, and will have less overall post-treatment impairment in anterograde and retrograde memory, less subjective memory complaints, and greater satisfaction with their treatment, compared to patients receiving ECT and placebo. 3) It is also expected that T3 will lower seizure threshold and enhance seizure duration in patients receiving ECT. 4) Finally, it is expected that patients receiving the combined treatment will exhibit a significant decrease in circulating T4 from pre- to post-treatment, and that the degree of clinical improvement will be directly associated with diminished T4 levels. The proposed study will test these hypotheses in 60 men and women, hospitalized at the UNC Neuropsychiatric Hospital. Patients will be randomly assigned, in a double-blind manner, to receive ECT with or without adjunctive T3. Neuropsychological and clinical assessments will be obtained at baseline, at regular intervals throughout treatment, 3-5 days following treatment, and at a one month post-treatment follow-up. Results of this study may have important clinical and economic ramifications by accelerating the antidepressant effects of ECT and diminishing the morbidity associated with this treatment.
