Bias and causal associations in observational research

Background: A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment. Methods: Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related...

Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement

The National Depressive and Manic-depressive Association (DMDA) survey of bipolar members

http://apsychoserver.psych.arizona.edu/JJBAReprints/PSYC501A/Readings/Harmon-Jones%20Gable%20Peterson%20Bio%20Psychology%202010.pdf

The role of asymmetric frontal cortical activity in emotion-related phenomena: a review and update.

The Altman Self-Rating Mania Scale

• We report the reliability and validity of the Internal State Scale, a self-report instrument for the simultaneous assessment of severity of manic and depressive symptoms The Internal State Scale consists of four empirically derived subscales: Activation, Well-Being, Perceived Conflict, and the Depression Index All subscales had good internal consistency reliability Activation subscale scores were significantly higher in manic patients than in depressed patients or control subjects, while Well-Being subscale scores were significantly lower and the Depression Index subscale scores were significantly higher in depressed patients than in the other two groups Activation subscale scores were correlated specifically with clinician ratings of mania Depression Index subscale scores were correlated specifically with clinician ratings of depression Further evidence for the validity of the subscales of the Internal State Scale in reflecting manic or depressive symptoms came from discriminant function analysis in which these subscales assigned 88% of subjects to the correct diagnostic groups In affectively ill patients who were studied in two or more mood states, Activation, Depression Index, and Well-Being subscale scores changed significantly in the predicted directions, while the same discriminant algorithm assigned 79% of mood states to the correct diagnostic category Bimodal distribution of scores of manic patients on the Well-Being and Depression Index subscales substantiated earlier findings that euphoric mood is not an essential feature of mania Based on findings from this and previous studies, the hypothesis is proposed that variables related to activation level, and not to mood state, constitute the core characteristics of the manic syndrome

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=PSYCH&articleId=495489&pdfFileName=archpsyc_48_9_005.pdf

Independent assessment of manic and depressive symptoms by self-rating. Scale characteristics and implications for the study of mania.

• Eleven patients with rapid cycling bipolar affective disorder whose symptoms were refractory to their current medication regimen were entered into an open trial of high-dose levothyroxine sodium added to a stable regimen of those medications. At baseline, all patients exhibited a rapid cycling pattern and were evaluated prospectively through at least one affective episode. Levothyroxine was added to the baseline medication regimen, and the dosage was increased until clinical response occurred or until side effects precluded further increase. While patients were taking levothyroxine, scores on both depressive and manic symptom rating scales decreased significantly compared with baseline. This improvement was due to the clear-cut response of depressive symptoms in 10 of 11 patients, with manic symptoms responding in five of the seven patients who exhibited them during baseline evaluation. Four patients then underwent singleor double-blind placebo substitution; three patients relapsed into either depression or cycling. Treatment response did not depend on previous thyroid status. In 9 of 10 responsive patients, supranormal circulating levels of free thyroxine were necessary to induce clinical response. Side effects were minimal, and there were no signs or symptoms of levothyroxine-induced hypermetabolism.

/pdf/rapid-cycling-bipolar-affective-disorder-ii-treatment-of-1x8ptw11n6.pdf

Rapid Cycling Bipolar Affective Disorder: II. Treatment of Refractory Rapid Cycling With High-Dose Levothyroxine: A Preliminary Study

• Thirty patients with rapid cycling bipolar affective disorder were studied prospectively to assess presence and severity of thyroid hypofunction. Seven (23%) were classified as having grade I hypothyroidism, while 8 (27%) had grade II and 3 (10%) had grade III abnormalities. This prevalence of grade I hypothyroidism is significantly greater than that reported in studies of unselected bipolar patients during long-term treatment with lithium carbonate, although only 63% of this sample of rapid cycling patients was taking lithium carbonate or carbamazepine. The association of rapid cycling with grade I hypothyroidism cannot be accounted for by lithium carbonate use or by the preponderance of women among rapid cycling patients. These findings (1) indicate that hypothyroidism during bipolar illness is a risk factor for the development of rapid cycling, and (2) leads to the hypothesis that a relative central thyroid hormone deficit occurring in bipolar patients predisposes to a rapid cycling course.

/pdf/rapid-cycling-bipolar-affective-disorder-i-association-with-2h8rshsi23.pdf

Mark S. Bauer

Papers

Independent assessment of manic and depressive symptoms by self-rating. Scale characteristics and implications for the study of mania.

Rapid Cycling Bipolar Affective Disorder: II. Treatment of Refractory Rapid Cycling With High-Dose Levothyroxine: A Preliminary Study

Rapid Cycling Bipolar Affective Disorder: I. Association With Grade I Hypothyroidism

Measurement of tissue lithium concentration by lithium magnetic resonance spectroscopy in patients with bipolar disorder.

Intensity and precision of circadian wheel running in three outbred rat strains