Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Sep 30;11(19):5830.
doi: 10.3390/jcm11195830.

A New Treatment Protocol of Combined High-Dose Levothyroxine and Repetitive Transcranial Magnetic Stimulation for the Treatment of Rapid-Cycling Bipolar Spectrum Disorders: A Cohort Evaluation of 55 Patients

Antonis C Zamar  1 , Christos Kouimtsidis  1   2 , Abbi Lulsegged  3 , Robin Roberts  4 , Theodoros Koutsomitros  5   6 , Daniel Stahl  7
Affiliations

A New Treatment Protocol of Combined High-Dose Levothyroxine and Repetitive Transcranial Magnetic Stimulation for the Treatment of Rapid-Cycling Bipolar Spectrum Disorders: A Cohort Evaluation of 55 Patients

Antonis C Zamar et al. J Clin Med. .

Abstract

Background: Bipolar spectrum disorders (BSD) are highly disabling, with rapid cycling being treatment resistant. High-dose levothyroxine (HDT) has been reported to be effective. Diagnosis is associated with mutations in thyroid-activating enzymes and cerebral transporter protein carrier. Repetitive transcranial magnetic stimulation (rTMS) has neuroplastic effects. Methods: We report data on 55 severely symptomatic patients with rapid-cycling BSD treated with a combination protocol of HDT and rTMS. Of the patients, 31 patients (56.4%) were female and 40 (72.7%) had at least one additional diagnosis. Results: Patients were evaluated at three monthly intervals after acute treatment. Remission was measured using the Sheehan Disability Scale (SDS). The average number of medications prescribed was 1.8, with 32 patients (58.2%) needing only levothyroxine. The average dose of levothyroxine was 303.7 mcg (50 mcg−1000 mcg). A total of 53 patients were in remission (96.4%), with an average duration of 2.0 years. The SDS scores decreased significantly (Cohen’s d = 2.61 (95% C.I. 1.81 to 2.83, p < 0.001). One patient had reversible side effects. A total of 52 (94.3%) patients had Deiodinase 1 and 2 (DiO1/DiO2) or SLCO1C1 protein carrier gene mutations. Conclusion: The data support the safety and acceptability of combined HDT/rTMS. Patients achieved long remissions with substantial improvements in quality of life.

Keywords: bipolar disorder; levothyroxine; repetitive transcranial magnetic stimulation (rTMS); thyroid test; treatment.

PubMed Disclaimer

Conflict of interest statement

The London Psychiatry Centre has pending patents for the treatment protocol in Europe and the US, with Zamar being the invento.

Figures

Figure 1
Figure 1
Box plots of severity of dependence scale (SDS) at start of treatment and at time of review. The central mark of the box shows the median value of the scores and the lower and upper top edges of the box indicate the 25th and 75th percentiles, respectively. Outliers are designated with a dot. The whiskers show the most extreme data points not considered outliers.
Figure 2
Figure 2
Shows the marginal means of T3 and T4 levels and T4/T3 ratio of the multilevel modelling analyses for pre, post, and final observation times.
See this image and copyright information in PMC

References

    1. Merikangas K.R., Jin R., He J.-P., Kessler R.C., Lee S., Sampson N.A., Viana M.C., Andrade L.H., Hu C., Karam E.G., et al. Prevalence and Correlates of Bipolar Spectrum Disorder in the World Mental Health Survey Initiative. Arch. Gen. Psychiatry. 2011;68:241–251. doi: 10.1001/archgenpsychiatry.2011.12. - DOI - PMC - PubMed
    1. Westman J., Hällgren J., Wahlbeck K., Erlinge D., Alfredsson L., Osby U. Cardiovascular mortality in bipolar disorder: A population-based cohort study in Sweden. [(accessed on 15 July 2022)];BMJ Open. 2013 3 doi: 10.1136/bmjopen-2012-002373. Available online: https://bmjopen.bmj.com/content/3/4/e002373. - DOI - PMC - PubMed
    1. Merikangas K.R., Akiskal H.S., Angst J., Greenberg P.E., Hirschfeld R.M., Petukhova M., Kessler R.C. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch. Gen. Psychiatry. 2007;64:543–552. doi: 10.1001/archpsyc.64.5.543. - DOI - PMC - PubMed
    1. Angst J. The Bipolar Spectrum. Br. J. Psychiatry. 2007;190:189–191. doi: 10.1192/bjp.bp.106.030957. - DOI - PubMed
    1. Kramlinger K.G., Post R.M. Ultra-rapid and ultradian cycling in bipolar affective illness. Br. J. Psychiatry. 1996;168:314–323. doi: 10.1192/bjp.168.3.314. - DOI - PubMed

LinkOut - more resources