Thyroid indices and response to fluoxetine and nortriptyline in major depression

We investigated: (i) the status of thyroid hormones and their clinical correlates in patients with major depression; (ii) changes in thyroid hormone status after treatment with fluoxetine versus nortriptyline; and (iii) whether blunted thyrotropin-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) challenge predicts improvement after 6 weeks of fluoxetine versus nortriptyline treatment. Patients with major depression entering a treatment trial were assessed with the Structured Clinical Interview for DSM-III-R and were rated on the Montgomery-Asberg Depression Rating Scale (MADRS). Blood samples were taken for TSH, thyroxine (T4) and free thyroxine (FT4) measurement, and the maximum TSH response (deltamaxTSH) to a TRH challenge test was undertaken. Patients were then randomly assigned to receive fluoxetine or nortriptyline for six weeks. At 6 weeks, patients repeated the thyroid hormone assessment and completed the MADRS. Mean concentrations of TSH, T4, FT4 and deltamaxTSH were within reference ranges. T4 and FT4 levels decreased significantly after treatment in responders, but not in nonresponders. After treatment, deltamaxTSH concentrations decreased significantly in patients who responded to fluoxetine, and increased in patients who responded to nortriptyline. Patients with deltamaxTSH blunting at pretreatment were more likely to be male, to have higher MADRS scores and have a history of alcohol and drug dependence. Patients with a pretreatment deltamaxTSH of < 3.0 microm/ml showed greater improvement on the MADRS when treated with fluoxetine than if treated with nortriptyline. We observed a decrease in T4 and FT4 in responders to treatment with fluoxetine or nortriptyline. Positive relationships between deltamaxTSH blunting and alcohol and drug abuse and severity of depression were found. Patients with blunted deltamaxTSH responded better to fluoxetine than to nortriptyline. It is suggested that a blunted DmaxTSH may reflect a predominantly serotonergic disturbance in this group of patients with major depression.