Improvement of Treatment Resistant Depression in a Patient With Primary Hypothyroidism and Thr92Ala5’ Type 2 Deiodinase Gene Polymorphism With Multiple Daily Doses of Triiodothyronine

Introduction: The augmentation pharmacologic therapy used in patients with treatment-resistant depression (TRD) includes drugs such as lithium, buspirone, triiodothyronine (LT3) and other drugs. We report a patient with TRD and primary hypothyroidism who responded to a combination of LT3, given in divided doses, and levothyroxine (LT4), rather than LT4 alone, even though the serum TSH levels were in the normal range with these treatments. Interestingly, the patient had a Thr92Ala5’ type 2 deiodinase polymorphism. Case Report: A 54-year old male presented to our emergency room with suicidal ideation 8 years ago. The patient had severe depression and developed uncontrollable urges to surf the internet, generally prohibited sites, approximately 3 months prior to his visit to the emergency room. He had noted a 12-lbs weight gain, cold intolerance, dry skin, and excessive sleepiness for 3 months. Patient was admitted to the psychiatry ward and laboratory testing showed a serum TSH 180 µIU/mL, FT4 0.48 ng/dL, total T3 46 ng/mL, and TPO antibody 278 IU/mL. A thyroid ultrasound was consistent with Hashimoto’s thyroiditis. A diagnosis of major depressive disorder and primary hypothyroidism was made. He was started on citalopram (20 mg/day) and levothyroxine (175 mcg/day). The Beck Depression Scores (BDS) during the initial weeks was 37.5 ± 5.1 (Mean ± SD) (normal 0-9) with corresponding TSH 164 ± 133 µIU/mL, FT4 0.70 ± 0.25 ng/dL, and total T3 61 ± 7.9 ng/mL. Two weeks later the dose of citalopram was increased to 40 mg/day and then buspirone 10 mg/day was added. At the end of 11 months the BDS was 27.81 ± 2.1 with a corresponding TSH 1.5 ± 0.1 µIU/mL. After 4 months, 7.5 mg of aripiprazole was added. After 11 months of treatment, he was treated with a combination of LT4 + LT3 (5 mcg once daily) and TSH became 0.76 ± 0.1 µIU/mL with a corresponding BDS of 18.0 ± 1.9. Twelve months later, the patient was switched back to LT4 alone and during LT4 treatment the BDS score was 24.2 ± 22.2 with a TSH of 1.44 ± 0.11. Nine months later patient was changed to LT4 + LT3 (5 mcg three times daily) and his BDS score was 10.3 ± 1.2 with a TSH of 0.72 ± 0.09 µIU/mL. When he was on LT4 + LT3 TID he was able to discontinue all the antidepressant drugs and he had no urge to surf on internet. His depression was controlled by over-the-counter antidepressant drugs (S-adenosylmethionine and rhodiola). A genetic test confirmed Thr92Ala5’ type 2 deiodinase polymorphism. Discussion and Conclusion: In our patient, there was a good correlation between the BDS improvement and the serum T3 levels (r: -0.7 p-value: 0.01). Thus, in patient with Thr92Ala5’ type 2 deiodinase polymorphism TID T3 dosing may significantly improve depression. Additional studies are needed.