Table 4.
Selected characteristics of clinical trials of combination therapy
| Authors | LT3 Dosing frequency | Approximate mcg ratio of T4:T3 | Serum T3 or FT3 higher in T4/T3 arm? | Trial duration | Neurocognitive measures | QOL, mood, measures | Genotyping done to assess effect of Thr92Ala? |
|---|---|---|---|---|---|---|---|
| Appelhof (10:1), 2005 | Twice daily | 10:1 | Yes | 15 wk | No diff | No diff | No |
| Appelhof (5:1), 2005 | Twice daily | 5:1 | Yes | 15 wk | No diff | No diff | No |
| Bunevicius, 1999 | Once daily | 10:1 | Yes | 5 wk | ↑ combo | ↑ combo | No |
| Bunevicius, 2002 | Once daily | 6.5:1 | No | 5 wk | No diff | No diff (tendency combo) | No |
| Clyde, 2003 | Twice daily | 6.5:1 | Yes | 4 mo | No diff | No diff | No |
| Escobar-Morreale, 2005 | Once daily | 15:1 or 12:1 | No | 8 wk | ↑ combo (some parameters only) | No diff | No |
| Fadeyev, 2010 | Once daily | 6:1 | NA | 6 mo | NA | NA | No |
| Hoang, 2013 | Once daily | 4:1 | Yes | 16 wk | No diff | No diff | No |
| Kaminski, 2016 | Once daily | 5:1 | No | 8 wk | NA | No diff | No |
| Nygaard, 2009 | Once daily | 4:1 | Yes (FT3 index) | 12 wk | NA | ↑ combo | Retrospective, yes |
| Rodriguez, 2005 | Once daily | 7:1 | Yes | 6 wk | No diff | No diff (no diff for fatigue) | No |
| Saravanan, 2005 | Once daily | 8:1 | No | 12 mo | NA | ↑ combo (3 mo only) (minority of measures) | Retrospective, yes |
| Sawka, 2003 | Twice daily | 3.5:1 | Yes | 15 wk | NA | No diff | No |
| Shakir, 2021 | Once daily | 9.5:1 | Yes | 22 wk | No diff (except in one domain in subgroup analysis of those with worst scores on LT4) | No diff (except in subgroup analysis of those with worst scores on LT4) | Prospective, no |
| Shakir, 2021 | Once daily | 4:1 | Yes | 22 wk | No diff (except in one domain in subgroup analysis of those with worst scores on LT4) | No diff (except in subgroup analysis of those with worst scores on LT4) | Prospective, no |
| Siegmund, 2004 | Once daily | 19:1 | No | 12 wk | No diff | No diff | No |
| Valizadeh, 2009 | Twice daily | 4:1 | Yes | 4 mo | NA | ↑ combo (minority of measures) | No |
| Walsh, 2003 | Once daily | 8.5:1 | No | 10 wk | No diff | No diff | No |
Italics indicate desiccated thyroid extract.
Abbreviations: diff, difference; FT3, free 3,5,3′-triiodothyronine; LT4, levothyroxine; NA, not assessed; QOL, quality of life; T3, 3,5,3′-triiodothyronine; T4, thyroxine.