Slower Treatment Response in Bipolar Depression Predicted by Lower Pretreatment Thyroid Function

Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
American Journal of Psychiatry (Impact Factor: 12.3). 02/2002; 159(1):116-21. DOI: 10.1176/appi.ajp.159.1.116
Source: PubMed


Because treatment of the depressed phase of bipolar disorder is a clinical challenge and hypothyroidism is known to be associated with depression, the authors examined the relationship between pretreatment thyroid values and response to antidepressant treatment. It was hypothesized that subjects with lower thyroid function, even within the normal range, would have a poorer response to initial treatment.
The subjects were 65 patients in the depressed phase of bipolar I disorder who were enrolled in a larger ongoing study. A panel of thyroid measures, including thyroid-stimulating hormone (TSH), thyroxine, triiodothyronine resin uptake, and free thyroxine index (FTI), were determined before initiation of algorithm-guided treatment. The effect of each thyroid measurement on time to remission was estimated by using the Cox proportional hazards model.
Both lower values of FTI and higher values of TSH were significantly associated with longer times to remission, i.e., slower response to treatment. Outcomes were relatively poor unless patients had FTI values above the median and TSH values below the median. Patients with this optimal profile experienced remission 4 months faster than the remainder of the study group.
This study provides further evidence that patients with bipolar disorder are particularly sensitive to variations in thyroid function within the normal range. Our results suggest that nearly three-quarters of patients with bipolar disorder have a thyroid profile that may be suboptimal for antidepressant response. It remains to be seen whether pharmacological enhancement of thyroid function will facilitate recovery from bipolar depression.

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    • "As reported by Cole et al. patients with bipolar depression and with optimal thyroid profile experienced remission 4 months faster than the remainder of the study group. This study provides further evidence that patients with bipolar disorder are particularly sensitive to variations in thyroid function within the normal range and nearly three-quarters of patients with bipolar disorder have a thyroid profile that may be suboptimal for antidepressant response [24]. "
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    ABSTRACT: The aim of this study is to investigate differences in thyroid-stimulating hormone (TSH) level in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania. Serum level of TSH was measured in 1,685 Caucasian patients (1,064 women, 63.1 %; mean age 46.4). Mean serum TSH concentration was: schizophrenia (n = 769) 1.71 μIU/mL, unipolar depression (n = 651) 1.63 μIU/mL, bipolar disorder (n = 264) 1.86 μIU/mL, bipolar depression (n = 203) 2.00 μIU/mL, bipolar mania (n = 61) 1.38 μIU/mL (H = 11.58, p = 0.009). Depending on the normal range used, the overall rate of being above or below the normal range was 7.9-22.3 % for schizophrenia, 13.9-26.0 % for unipolar depression, 10.8-27.6 % for bipolar disorder, 12.2-28.5 % for bipolar depression, and 11.4-24.5 % for bipolar mania. We have also found differences in TSH levels between the age groups (≤20, >20 years and ≤40, >40 years and ≤60 years and >60 years). TSH level was negatively correlated with age (r = - 0.23, p < 0.001). Weak correlations with age have been found in the schizophrenia (r = - 0.21, p < 0.001), unipolar depression (r = - 0.23, p < 0.001), bipolar depression (r = - 0.25, p = 0.002) and bipolar disorder (r = - 0.21, p = 0.005) groups. Our results confirm that there may be a higher prevalence of thyroid dysfunctions in patients with mood disorders (both unipolar and bipolar) and that these two diagnostic groups differ in terms of direction and frequency of thyroid dysfunctions.
    Neurochemical Research 04/2014; 39(7). DOI:10.1007/s11064-014-1305-3 · 2.59 Impact Factor
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    • "Similar findings during maintenance-phase treatment with lithium are consistent with the well-known anti-thyroid effects of lithium. Therefore, lithium-induced changes in thyroid function, even within the normal range, are detrimental to its prophylactic efficacy, especially with regard to depressive symptoms [85, 110, 113]. The presence of HPT dysfunction during lithium-treatment further underlines the need for regular monitoring of thyroid functions and rapid correction of any abnormalities that arise during such treatment. "
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    ABSTRACT: Accumulating evidence suggests that hypothalamo-pituitary-thyroid (HPT) axis dysfunction is relevant to the pathophysiology and clinical course of bipolar affective disorder. Hypothyroidism, either overt or more commonly subclinical, appears to the commonest abnormality found in bipolar disorder. The prevalence of thyroid dysfunction is also likely to be greater among patients with rapid cycling and other refractory forms of the disorder. Lithium-treatment has potent antithyroid effects and can induce hypothyroidism or exacerbate a preexisting hypothyroid state. Even minor perturbations of the HPT axis may affect the outcome of bipolar disorder, necessitating careful monitoring of thyroid functions of patients on treatment. Supplementation with high dose thyroxine can be considered in some patients with treatment-refractory bipolar disorder. Neurotransmitter, neuroimaging, and genetic studies have begun to provide clues, which could lead to an improved understanding of the thyroid-bipolar disorder connection, and more optimal ways of managing this potentially disabling condition.
    Journal of Thyroid Research 07/2011; 2011(3):306367. DOI:10.4061/2011/306367
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    • "u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j a d Thyroid abnormalities have also been linked to abnormal mood states in bipolar disorder. Thyroid abnormalities have been associated with rapid-cycling (Cowdry et al., 1983; Bartalena et al., 1990; Oomen et al., 1996), mixed states (Chang et al., 1998), and slower treatment response (Cole et al., 2002). There are no double-blind studies reporting the use of thyroid hormone in bipolar patients (Sachs and Thase, 2000). "
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    ABSTRACT: Thyroid hormone plays a role in both serotonin and catecholamine functions in the brain, and has been linked to abnormal mood states in bipolar disorder. Unlike most studies which have included only patients with bipolar I, this study evaluated triiodothyronine (T3) as an augmentation agent for treatment-resistant depression in patients with bipolar II and bipolar disorder NOS. This study was a retrospective chart review of patients treated in a private clinic between 2002 and 2006. The charts of 125 patients with bipolar II disorder and 34 patients with bipolar disorder NOS were reviewed. Patients had been unsuccessfully treated with an average of 14 other medications before starting T3. At an average dose of 90.4 mcg (range 13 mcg-188 mcg) the medication was well tolerated. None of the patients experienced a switch into hypomania, and only 16 discontinued due to side effects. Improvement was experienced by 84%, and 33% experienced full remission. The limitations are those associated with the retrospective chart review design. A high percentage of bipolar II and bipolar NOS patients with treatment resistant depression improved on T3. Despite the use of higher than usual doses in many of the patients, the medication was well tolerated. Augmentation with supraphysiologic doses of T3 should be considered in cases of treatment resistant bipolar depression.
    Journal of Affective Disorders 03/2009; 116(3):222-6. DOI:10.1016/j.jad.2008.12.010 · 3.38 Impact Factor
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