Acceleration and Relapse Prevention With Triiodothyronine (T3) as an Adjunct to Electroconvulsive Therapy (ECT)
Condition: Depression
MeSH terms: Recurrence; Depression
Study type: Observational

Summary: 
      The purpose of this study is:

        -  To evaluate liothyronine (Cytomel) as an accelerating agent (i.e. faster rate to
           clinical remission) to electroconvulsive therapy.

        -  To evaluate whether thyroid supplement acceleration can reduce the neurocognitive side
           effect of ECT treatment.

        -  To evaluate whether thyroid status at the time of remission is associated with
           subsequent relapse rate.

        -  To evaluate genetic polymorphisms in enzymes responsible for thyroid metabolism and the
           serotonin transporter promoter gene in depression (5-HTTLRP).
    

Detailed description: 
      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.
    

Intervention name(s): T3
Intervention type(s): Drug
Intervention description(s): Given each day of ECT treatment 25 mg for the first 5 days increasing to 50 mg for the duration of treatment.
Other intervention name(s): triiodythronine
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        Consultants at the Department of Psychiatry and Psychology will evaluate patients with a
        diagnosis of depression (unipolar) for ECT. When a patient matches the study's diagnostic
        criteria, and does not meet any of the exclusion criteria, he/she will be asked to
        participate in the study.

        Patient will be contacted prior to first ECT Treatment by study personnel
      
Biospecimen description: 
      Thyroid measures at time of sustained response will include free T3, free T4, and TSH. All
      draws will be done before ECT treatment. An additional free T3 will be obtained at the second
      visit that confirms sustained response. The mean free T3 will be used as the outcome measure.
      If a suppressed TSH is found, a TSH be repeated 1 week later. At the beginning of the study
      30 mL of blood will be drawn and a portion of the collected blood sample will undergo DNA
      extraction. The extracted DNA will undergo genetic analysis. The remainder owill be
      immortalized and stored for future study. Blood will be drawn into 1 10-mL EDTA tube and 2
      10-mL Heparin tubes . Samples will be stored at Mayo Clinic BAP Lab for subsequent DNA
      extraction, analysis, and storage.