Table 2.

Sensitivity analyses on subclinical hypothyroidism and depressive symptoms at first available follow-up*

Sensitivity analysis	No. of participants		No. of included studies†	MD in BDI score (95% CI), I2
	Euthyroid	SHypo
Main analysis	21,025	1342	6	0.29 (− 0.17–0.76) §, 15.6%
1) Excluding participants with thyroid medication	20,268	1123	6	0.30 (− 0.15–0.75), 4.7%
2) Excluding participants with thyroid altering medication	20,261	1123	6	0.30 (− 0.15–0.76), 4.8%
3) Excluding participants with antidepressant medication	20,897	1327	6	0.32 (− 0.19–0.83), 26.1%
4) Excluding participants with dementia	20,203	1222	6	0.24 (− 0.17–0.65), 0.0%
5) Excluding participants without FT4 measurement	4550	1068	5	0.17 (− 0.49–0.83), 11.8%
6) Using multiple imputation to impute missing outcome data	42,759	2639	6	0.35 (− 0.10–0.81), 10.7%
7) Including studies without depressive symptoms at baseline	25,851	1510	9	0.25 (− 0.13–0.63), 0.0%
8) Not adjusted for income	21,509	1413	6	0.22 (− 0.22, 0.65), 11.1%
9) Excluding HUNT	6210	833	5	0.54 (0.04, 1.05), 0.0%
			SMD in depressive symptoms (95% CI), I2
10) Using original scale for depressive symptoms‡	21,025	1342	6	0.04 (− 0.02–0.09), 27.2%

SHypo subclinical hypothyroidism; TSH thyroid-stimulating hormone; FT4 free thyroxine; MD mean difference; SMD standardised mean difference; BDI Score Beck DEPRESSION INVENTORY SCORE (range 0–63, minimal clinically important difference 5 points); CI confidence Interval; No number.

*Analyses adjusted for depressive symptoms at baseline (In sensitivity analysis 7: except studies without measurement), sex, age, income, and education (The CHS, Health ABC Study, and the InChianti Study were additionally adjusted for income).

^†The main analysis includes the same studies as for the primary outcome analysis: Leiden 85 + ¹³, PROSPER¹¹, Health ABC Study⁴⁶, CHS³², InChianti Study⁴⁷, HUNT⁴⁸.

Sensitivity analyses 1–4, 6, 8, 10: the same studies as in the main analysis were included, only participants with a certain measurement missing were excluded.

Sensitivity analysis 5: the same studies as in the main analysis without the Health ABC Study ³² because in this study FT4 was not measured in the euthyroid group.

Sensitivity analysis 7: the same studies as in the main analysis plus 3 studies that did not have data for depressive symptoms at baseline were included (PREVEND (Prevention of Renal and Vascular end-stage Disease)⁴⁹, MrOS (Osteoporotic Fractures in Men)⁵⁰, SHIP (Study of Health in Pomerania)⁵¹).

Sensitivity analysis 9: the same studies as in the main analysis without the HUNT⁴⁸ study as the HUNT study has the biggest weight in the summarized result of the main outcome (34.96%).

^‡Mean differences using the original scale for depressive symptoms within each study were pooled.

^§Overall mean BDI score at first follow-up of all 23,038 participants was 10.67 with a standard deviation of 8.97.