Effect of Levothyroxine Therapy on the Development of Depressive Symptoms in Older Adults With Subclinical Hypothyroidism: An Ancillary Study of a Randomized Clinical Trial.

Wildisen, Lea; Feller, Martin; Del Giovane, Cinzia; Moutzouri, Elisavet; Du Puy, Robert S; Mooijaart, Simon P; Collet, Tinh-Hai; Poortvliet, Rosalinde K E; Kearney, Patricia; Quinn, Terence J; Klöppel, Stefan; Bauer, Douglas C; Peeters, Robin P; Westendorp, Rudi; Aujesky, Drahomir; Gussekloo, Jacobijn; Rodondi, Nicolas (2021). Effect of Levothyroxine Therapy on the Development of Depressive Symptoms in Older Adults With Subclinical Hypothyroidism: An Ancillary Study of a Randomized Clinical Trial. JAMA network open, 4(2), e2036645. 10.1001/jamanetworkopen.2020.36645

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Importance

Previous trials on the effect of levothyroxine on depressive symptom scores in patients with subclinical hypothyroidism were limited by small sample sizes (N = 57 to 94) and potential biases.

Objective

To assess the effect of levothyroxine on the development of depressive symptoms in older adults with subclinical hypothyroidism in the largest trial on this subject and to update a previous meta-analysis including the results from this study.

Design, Setting, and Participants

This predefined ancillary study analyzed data from participants in the Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism (TRUST) trial, a double-blind, randomized, placebo-controlled, parallel-group clinical trial conducted from April 2013 to October 31, 2016. The TRUST trial included adults aged 65 years or older diagnosed with subclinical hypothyroidism, defined as the presence of persistently elevated thyroid-stimulating hormone (TSH) levels (4.6-19.9 mIU/L) with free thyroxine (T4) within the reference range. Participants were identified from clinical and general practitioner laboratory databases and recruited from the community in Switzerland, the Netherlands, Ireland, and the UK. This ancillary study included a subgroup of 472 participants from the Netherlands and Switzerland; after exclusions, a total of 427 participants (211 randomized to levothyroxine and 216 to placebo) were analyzed. This analysis was conducted from December 1, 2019, to September 1, 2020.

Interventions

Randomization to either levothyroxine or placebo.

Main Outcomes and Measures

Depressive symptom scores after 12 months measured with the Geriatric Depression Scale (GDS-15), with higher scores indicating more depressive symptoms (minimal clinically important difference = 2).

Results

A total of 427 participants with subclinical hypothyroidism (mean [SD] age, 74.52 [6.29] years; 239 women [56%]) were included in this analysis. The mean (SD) TSH level was 6.57 (2.22) mIU/L at baseline and decreased after 12 months to 3.83 (2.29) mIU/L in the levothyroxine group; in the placebo group, it decreased from 6.55 (2.04) mIU/L to 5.91 (2.66) mIU/L. At baseline, the mean (SD) GDS-15 score was 1.26 (1.85) in the levothyroxine group and 0.96 (1.58) in the placebo group. The mean (SD) GDS-15 score at 12 months was 1.39 (2.13) in the levothyroxine and 1.07 (1.67) in the placebo group with an adjusted between-group difference of 0.15 for levothyroxine vs placebo (95% CI, -0.15 to 0.46; P = .33). In a subgroup analysis including participants with a GDS-15 of at least 2, the adjusted between-group difference was 0.61 (95% CI, -0.32 to 1.53; P = .20). Results did not differ according to age, sex, or TSH levels. A previous meta-analysis (N = 278) on the association of levothyroxine with depressive symptoms was updated to include these findings, resulting in an overall standardized mean difference of 0.09 (95% CI, -0.05 to 0.22).

Conclusions and Relevance

This ancillary study of a randomized clinical trial found that depressive symptoms did not differ after levothyroxine therapy compared with placebo after 12 months; thus, these results do not provide evidence in favor of levothyroxine therapy in older persons with subclinical hypothyroidism to reduce the risk of developing depressive symptoms.

Trial Registration

ClinicalTrials.gov Identifier: NCT01853579.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > University Psychiatric Services > University Hospital of Geriatric Psychiatry and Psychotherapy
04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine > Centre of Competence for General Internal Medicine
04 Faculty of Medicine > Medical Education > Institute of General Practice and Primary Care (BIHAM)
04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine

Graduate School:

Graduate School for Health Sciences (GHS)

UniBE Contributor:

Wildisen, Lea Franziska; Feller, Martin; Del Giovane, Cinzia; Moutzouri Beifuss, Elisavet; Klöppel, Stefan; Aujesky, Drahomir and Rodondi, Nicolas

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

2574-3805

Funders:

[4] Swiss National Science Foundation ; [116] Swiss Heart Foundation = Schweizerische Herzstiftung

Language:

English

Submitter:

Doris Kopp Heim

Date Deposited:

11 Feb 2021 12:00

Last Modified:

13 Mar 2021 20:43

Publisher DOI:

10.1001/jamanetworkopen.2020.36645

PubMed ID:

33566107

BORIS DOI:

10.48350/152159

URI:

https://boris.unibe.ch/id/eprint/152159

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