SUBCLINICAL HYPOTHYROIDISM IN TREATMENT-RESISTANT DEPRESSION

Objective: To critically evaluate the relevance of subclinical hypothyroidism (SCH) to treatment-resistant depression (TRD), with particular attention to diagnostic distinctions and thyroid-directed therapeutic strategies.
Methodology: A narrative review of a predefined set of 13 full-text publications was undertaken. Study populations, thyroid classification, psychiatric ascertainment, interventions, numerical findings and limitations were extracted and compared. No systematic literature search or new quantitative synthesis was performed.
Results: The two included meta-analyses reached different conclusions about the SCH–depression association, including conflicting age-related findings. Neither intervention synthesis demonstrated statistically significant improvement in depressive outcomes with levothyroxine (LT4). A high SCH prevalence in selected untreated major depressive disorder populations did not establish antidepressant resistance. Other studies concerned symptom dimensions, mixed unipolar and bipolar populations, or previously treated hypothyroidism without contemporaneous biochemical assessment. Proposed mechanisms involving central hormone availability, autoimmunity, inflammatory mediators and deiodinase variation remain insufficiently validated for treatment selection. A favourable LT4/liothyronine combination-treatment case involved severe overt hypothyroidism and cannot establish efficacy in SCH.
Conclusion: SCH should not be assumed to explain antidepressant nonresponse. Thyroid replacement and liothyronine augmentation have distinct therapeutic objectives. Careful biochemical classification and independent psychiatric assessment are warranted, while direct controlled evidence in persistent SCH with rigorously characterised TRD remains insufficient within this reference set.