Jeffrey S. Simon

Subclinical Hypothyroidism: A Review of Neuropsychiatric Aspects

The authors review current information about the prevalence, causes, course, and consequences of subclinical hypothyroidism. There is evidence that subclinical hypothyroidism may be associated with cognitive dysfunction, mood disturbance, and diminished response to standard psychiatric treatments. Recommendations are presented for the screening, evaluation and treatment of patients in whom subclinical hypothyroidism may be contributing to neuropsychiatric dysfunction.

The presence of antithyroid antibodies in patients with affective and nonaffective psychiatric disorders

We determined the frequency of antithyroglobulin and antimicrosomal antibodies in 173 consecutively admitted psychiatric inpatients. (We found antithyroid antibodies in 8% (5/65) of patients with DSM-III major depression, 13% (4/31) with biploar disorder, and in 0% (0/4) of those with schizoaffective disorder.) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole. The overall frequency of positive antithyroid antibody titers in patients with DSM-III affective disorder, 9% (9/99), did not differ from that in patients with nonaffective disorders, 10% (7/68). However, patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients. Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder, even in the absence of lithium exposure. However, as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders, the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation.

Estimates of serotonin and norepinephrine transporter inhibition in depressed patients treated with paroxetine or venlafaxine.

Paroxetine and venlafaxine are potent serotonin transporter (SERT) antagonists and weaker norepinephrine transporter (NET) antagonists. However, the relative magnitude of effect at each of these sites during treatment is unknown. Using a novel blood assay that estimates CNS transporter occupancy we estimated the relative SERT and NET occupancy of paroxetine and venlafaxine in human subjects to assess the relative magnitude of SERT and NET inhibition. Outpatient subjects (N=86) meeting criteria for major depression were enrolled in a multicenter, 8 week, randomized, double-blind, parallel group, antidepressant treatment study. Subjects were treated by forced-titration of paroxetine CR (12.5–75 mg/day) or venlafaxine XR (75–375 mg/day) over 8 weeks. Blood samples were collected weekly to estimate transporter inhibition. Both medications produced dose-dependent inhibition of the SERT and NET. Maximal SERT inhibition at week 8 for paroxetine and venlafaxine was 90% (SD 7) and 85% (SD 10), respectively. Maximal NET inhibition for paroxetine and venlafaxine at week 8 was 36% (SD 19) and 60% (SD 13), respectively. The adjusted mean change from baseline (mean 28.6) at week 8 LOCF in MADRS total score was −16.7 (SE 8.59) and −17.3 (SE 8.99) for the paroxetine and venlafaxine-treated patients, respectively. The magnitudes of the antidepressant effects were not significantly different from each other (95%CI −3.42, 4.54, p=0.784). The results clearly demonstrate that paroxetine and venlafaxine are potent SERT antagonists and less potent NET antagonists in vivo. NET antagonism has been posited to contribute to the antidepressant effects of these compounds. The clinical significance of the magnitude of NET antagonism by both medications remains unclear at present.

The dexamethasone suppression test and antidepressant response in major depression

UNLABELLED We conducted a prospective open pilot study of 34 consecutively admitted patients with the DSM-III diagnosis of MD who were admitted to a general psychiatric unit. Patients underwent a 1 mg DST and were randomly assigned to treatment with either maprotiline or trazodone. Antidepressant dosages were increased as tolerated clinically and according to treatment response. RESULTS mean final oral doses were 193 mg for maprotiline and 328 mg for trazodone. The mean treatment duration was 4.5 weeks for maprotiline and 5.9 weeks for the trazodone group. Of these 34 patients 44% showed DST nonsuppression (41% maprotiline, 45% trazodone). Seventy-six per cent of the patients responded to treatment (76% for both drugs) as defined by GAS. Eighty-seven per cent of the nonsuppressors responded to treatment (86% maprotiline, 88% trazodone) and 68% of the suppressors responded (70% maprotiline, 67% trazodone). Of the eight treatment nonresponders six showed DST suppression. The implications of these findings are discussed.

Clinical Aspects of Neuropeptide Research

Increasing evidence suggests that depression is found in a high percentage of patients with cancer (Petty and Noyes 1981; Buckberg et al. 1984), but depression appears to be both underdiagnosed and inadequately treated in cancer patients. There is also a growing body of evidence suggesting that experimentally induced stress in animals as well as psychiatric illness and stressful life experience in humans are associated with alterations in both neuroendocrine and immune function. Alterations in immune function have been found in patients with major depression (Kronfol et al. 1983; Schliefer et al. 1984,1985), and there is one report suggesting an epidemiologic relationship between depression and cancer (Shekelle et al. 1981). However, it is not known whether the alterations in immune function found in depression are of clinical significance, and there have been no comprehensive studies of both neuroendocrine and immune function in depressed cancer patients.