The effect of levothyroxine therapy on depressive symptoms in adults with subclinical hypothyroidism

• Published in: European journal of public health Vol. 30; no. Supplement_5
• Main Authors: Wildisen, L, Del Giovane, C, Feller, M, Moutzouri, E, Mooijaart, S, Poortvliet, R, Du Puy, R, Peeters, R, Gussekloo, J, Rodondi, N
• Format: Journal Article
• Language: English
• Published: Oxford Oxford Publishing Limited (England) 01-09-2020
• Subjects: Adults; Clinical trials; Confidence intervals; Hypothyroidism; Medical treatment; Mental depression; Patients; Placebos; Public health; Regression analysis; Regression models; Statistical analysis; Systematic review; Therapy; Thyroxine
• ISSN: 1101-1262; 1464-360X
• DOI: 10.1093/eurpub/ckaa165.823

Abstract
Background
Levothyroxine is one of the most commonly prescribed drugs. A common reason for levothyroxine treatment on patients with subclinical hypothyroidism are depressive symptoms. A meta-analysis of four RCTs (n = 278) found no benefit of levothyroxine therapy on depressive symptoms. However, the confidence interval does not exclude a small clinical benefit. We aim to assess the effect of levothyroxine therapy for depressive symptoms in patients with subclinical hypothyroidism using data from a RCT with more than 400 adults.
Methods
The TRUST trial was a double-blind, randomized, placebo-controlled trial involving adults aged ≥65y with subclinical hypothyroidism (elevated TSH levels (4.6-19.9 mU/L) and free thyroxine within the reference range). The outcome was depressive symptoms after 12 months based on the Geriatric Depression Scale (GDS-15), a 15-item questionnaire (range: 0 to 15, higher scores indicate more depressive symptoms, minimal clinical important difference: 2). The multivariable linear regression model was adjusted for levothyroxine starting dose, sex, site, and GDS-15 baseline score.
Results
425 Swiss and Dutch adults with subclinical hypothyroidism were randomised (mean age 75y, 56% female). The mean (SD) TSH was 6.6 (2.1) mU/L at baseline and after 12 months decreased to 3.8 (2.3) mU/L in the levothyroxine group vs 5.9 (2.7) mU/L in the placebo group. At baseline, the mean GDS-15 score was 1.3 (1.9) in the levothyroxine group and 1.0 (1.6) in the placebo group. The mean GDS-15 score at 12 months was 1.4 (2.1) in the levothyroxine and 1.1 (1.7) in the placebo group with an adjusted between-group difference of 0.2 for levothyroxine vs. placebo (95% CI:-0.1 to 0.5; p = 0.29).
Conclusions
In this by far largest RCT on the topic, levothyroxine therapy did not confer a benefit for depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine for depressive symptoms when they co-occur with subclinical hypothyroidism.
Key messages
Levothyroxine has no benefit on depressive symptoms in patients with subclinical hypothyroidism. Levothyroxine prescription to patients with subclinical hypothyroidism and depressive symptoms should be reconsidered.