Acceleration and Relapse Prevention With Triiodothyronine (T3) as an Adjunct to Electroconvulsive Therapy (ECT)

This is a single-site, randomized, placebo-controlled trial of concurrent triiodothyronine
(Cytomel® 25-50 mcg/d) to electroconvulsive therapy (ECT) in patients with a major
depressive episode referred to ECT. Goals of this application are to: 1) evaluate whether
thyroid status at time of sustained clinical response is associated with subsequent relapse
rate, 2) evaluate triiodothyronine (Cytomel®) as an accelerating agent (i.e. faster rate to
sustained clinical response) to electroconvulsive ECT treatment, and 3) evaluate whether
thyroid acceleration can reduce the neurocognitive side effects of ECT. 4) To evaluate
genetic polymorphisms in enzymes responsible for thyroid metabolism and the serotonin
transporter promoter gene in depression (5-HTTLRP).

The primary outcome measure for this study, time to relapse, is defined as a Hamilton
Depression Score (HAMD-24) ≥16 and an increase of ≥10 points from sustained response
baseline. Secondary outcomes measures are time to sustained response, defined as a ≥60%
reduction in the HAMD-24 score, and neurocognitive side effect burden as rated by the
modified Mini Mental Status Examination at time of sustained clinical response.

Hypotheses:

1. Within a 6-month study period, mean serum free T3 at time of sustained clinical
response will correlate with time to subsequent relapse [defined as a HAMD-24 score ≥16
with an increase of ≥10 points from baseline (sustained response)].

2. In comparison to placebo, triiodothyronine (Cytomel®, 25-50 mcg) will accelerate time
to sustained clinical response [defined as a ≥60% reduction in the Hamilton Rating
Scale for Depression, 24-item, (HAMD-24) score and a HAMD-24 total score ≤10 for 2
consecutive visits] in depressed patients referred to ECT.

3. In comparison to placebo, at time of sustained clinical response, there will be less
ECT-related neurocognitive side effects, as rated by the modified Mini-Mental Status
Examination (mMMSE), associated with triiodothyronine.

4. a. The 5-HTTLPR long allele (l) and (l)/(l) genotype will be associated with a faster
treatment response.

b. The DI-C785T allele will be associated with lower T3 levels at baseline and faster
treatment response.