Clinical and subclinical hypothyroidism in patients with chronic and treatment-resistant depression

To investigate the relationship between hypothyroidism and treatment-resistant depression (TRD).

A retrospective case audit of 93 inpatients of a specialist Mood Disorders Unit. Patients referred with TRD were sub-classified into 'adequate' or 'inadequate' prior treatment groups on the basis of pre-established criteria, and compared with a 'non-TRD' control sample. Grades I (clinical) and II (subclinical) hypothyroidism were determined by review of relevant thyroid indices.

Patients had chronic depressive disorders (sub-group means of 57.5-82.2 weeks of illness). Of those patients referred with TRD, 22% (10/46) had evidence of clinical or subclinical hypothyroidism compared with 2% (1/47) of the non-TRD patients (p < 0.01). A gradient in the rates of grade I hypothyroidism was observed with the adequately-treated TRD patients having the highest rate (13%), the inadequately-treated TRD patients having an intermediate rate (7%), and the non-TRD patients having the lowest rate (2%). Consistent with this view, the inadequately-treated TRD group had the highest rate of grade II hypothyroidism (p = 0.01) and tended to have higher thyroid stimulating hormone (TSH) values (p = 0.06). Differences in the rates of hypothyroidism could not be accounted for by differences in age or prior exposure to lithium and/or carbamazepine. Duration of the depressive episode was negatively correlated with both the free thyroxine indices (r = -0.25, P < 0.05) and TSH levels (r = -0.32, p < 0.01).

This study suggests that relative hypothyroidism may play a role in the development of some treatment-resistant depressive disorders.