High-Dose Levothyroxine for Bipolar Disorder; the Potential Role of Thyroid Function and Genetic Tests. Report from Twenty Cases.

Abstract

Rationale: Rapid Cycling Bipolar Disorder (RCBPD) is a malignant course of bipolar disorder (BPD). The condition is associated with several co-morbidities and is difficult to treat. Supra- physiologic doses of levothyroxine (average 482 µg/day) (High-Dose Levothyroxine, HDL) have proven effective for treatment resistant BPD. It is unclear exactly how HDL benefits patients with BPD. Objectives: In this paper, we present the retrospective analysis of clinical notes of 20 patients in remission from RCBPD for at least six months, who received HDL (150-1000 µg; median 472 µg/day). We examine the role of Thyroid function tests (TFTs) and genetic testing. We aim to demonstrate the utility of these tests for patient selection and response prediction for HDL. Findings: All patients recovered with minimal side effects with no treatment discontinuations. One patient required a dose reduction because of palpitations and sweating. Seventeen patients had concomitant Repetitive Transcranial Magnetic Stimulation (rTMS). Ten patients (50%) required one psychotropic in the acute phase, two patients (10%) required two and eight patients (40%) required only HDL. Following remission, 11 patients (55%) were on HDL only. The average pre-treatment ratio of free T4 (thyroxine, fT4): free T3 (triiodothyronine, fT3) was 4:1, with fT4 increasing post-treatment to 5:1 while fT3 remained largely normal. Nineteen patients had single nucleotide polymorphism (SNPs) of DIO1, DIO2 , or both. One subject requiring 400 µg had a SNP in the SLCO1C1 thyroid carrier. A high fT4:fT3 noted as early as day 10 during treatment supports a role for DIO polymorphisms. Conclusions: This preliminary report demonstrates the usefulness of a high fT4/fT3 ratio in the second week as a predictive test for patient selection and response prediction for HDL. Recently we have developed a treatment protocol combining HDL and rTMS.