All subjects in the current study were recruited from a larger study of the dosing and efficacy of fluoxetine versus sertraline in the treatment of major depression.10
Subjects who agreed to have their peripheral thyroid hormones assayed before and after treatment with the SSRI gave written informed consent and were included in the current study. Nineteen subjects form the sample described in this report. Inclusion criteria were a current diagnosis of major depressive episode, as defined in the Diagnostic and Statistical Manual of Mental Disorders
, fourth edition,11
and age between 18 and 60 years. The diagnosis was made by a structured interview with trained raters. Exclusion criteria were as follows: 1) a history of substance abuse within the last 30 days; 2) current or recent treatment with an antidepressant; 3) history of previous manias or hypomanias; 4) previous failure of treatment with fluoxetine or sertraline; and 5) a history of thyroid disease or current treatment with thyroid hormones. No patient was treated with lithium before study entry.
At study entry, baseline clinical assessments included the 21-item Hamilton Depression Rating Scale (Ham-D)12
and the Clinical Global Impressions (CGI) Severity of Illness and Global Improvement scales.13
Subjects were then treated with sertraline, 50 mg daily (n
= 8), sertraline, 100 mg daily (n
= 4), or fluoxetine, 20 mg daily (n
= 7), with medication and dose assigned alternately, that is, patient 1 received sertraline, 50 mg, patient 2, sertraline, 100 mg, and patient 3, fluoxetine, but openly. At 6 weeks, subjects with a Ham-D score above 7 and a CGI Global Improvement score above 1 (less than “marked improvement”) had their daily doses increased to sertraline, 100 mg daily, sertraline, 200 mg daily, or fluoxetine, 40 mg daily, respectively. Total treatment time was 10 weeks. Although subjects were assessed every 2 weeks for 10 weeks, in this report, only the final CGI scores (both severity and improvement subscales) and Ham-D will be considered. Ham-D scores were assessed by research assistants and physicians who all had previous rating training.
At baseline, thyroid indices were measured using standard venipuncture techniques: TSH was assessed using solid-phase immunoradiometric assay, T4 by radioimmunoassay (RIA), T3 by RIA and free T4 by rabbit anti-T4 antibody (Diagnostic Products Kit). For all assays, the intra-assay and interassay variation were less than 10%. Thyroid tests were batch run. At the end of the study, the same thyroid indices were measured again. Two subjects did not complete the post- treatment thyroid measurements. Our sample, therefore, includes 19 subjects at baseline (12 on sertraline and 7 on fluoxetine) and post-treatment clinical evaluation, of whom 17 underwent thyroid evaluations both before and after treatment.
Hormone levels were screened for distributional properties and determined to be appropriate for parametric analysis. Paired t tests were used to evaluate changes in levels of TSH, T4, T3 and free T4 before and after treatment for the 17 patients with values from both time points. Response to treatment was measured by the change in Ham-D scores from before and after treatment, with positive values reflecting improvement in Ham-D symptoms. A stepwise regression analysis was used to predict improvement in Ham-D scores, with baseline values for TSH, T4, T3 and free T4 as the independent variables (n = 19).