Long-Term Lithium Therapy and Thyroid Disorders in Bipolar Disorder: A Historical Cohort Study

Abstract

Lithium has been a cornerstone treatment for bipolar disorder (BD). Despite descriptions in the literature regarding associations between long-term lithium therapy (LTLT) and development of a thyroid disorder (overt/subclinical hypo/hyperthyroidism, thyroid nodule, and goiter) in BD, factors such as time to onset of thyroid abnormalities and impact on clinical outcomes in the course of illness have not been fully characterized. In this study we aimed to compare clinical characteristics of adult BD patients with and without thyroid disorders who were on LTLT. We aimed to identify the incidence of thyroid disorders in patients with BD on LTLT and response to lithium between patients with and without thyroid disorders in BD. The Cox proportional model was used to find the median time to the development of a thyroid disorder. Our results showed that up to 32% of patients with BD on LTLT developed a thyroid disorder, of which 79% developed hypothyroidism, which was corrected with thyroid hormone replacement. We did not find significant differences in lithium response between patients with or without thyroid disorders in BD. Findings from this study suggest that patients with BD and comorbid thyroid disorders when adequately treated have a response to lithium similar to patients with BD and no thyroid disorders.

Low and very low lithium levels: Thyroid effects are small but still require monitoring

“…If TSH does increase after starting lithium, this does not necessarily warrant lithium's discontinuation, or correction with levothyroxine. Although high‐normal TSH levels have been associated with poor antidepressant response 38 and with rapid cycling 45 and mixed states, 46,47 increased TSH levels following the initiation of lithium can frequently normalize without further intervention 32,48 . Moreover, a recent review found that the effect size for the association between hypothyroidism and clinical depression was considerably lower than previously assumed, and the modest association was possibly restricted to overt hypothyroidism and female individuals 49 .…”

“…Although high-normal TSH levels have been associated with poor antidepressant response 38 and with rapid cycling 45 and mixed states, 46,47 increased TSH levels following the initiation of lithium can frequently normalize without further intervention. 32,48 Moreover, a recent review found that the effect size for the association between hypothyroidism and clinical depression was considerably lower than previously assumed, and the modest association was possibly restricted to overt hypothyroidism and female individuals. 49 Early testing with aggressive response to TSH increases could lead to unnecessary treatment or lithium discontinuation.…”

“…27,28 Such interest could improve or even reverse lithium's reputation, if thyroid effects of low lithium doses are small, because the downside of long-term use would also be small. Alternatively, if low doses carry a 10%-20% chance of hypothyroidism 29,30 -or even 30%, as shown in some studies of full-dose lithium 31,32 -that prospect might sustain public and professional lithium phobia.…”

Patterns of pharmacotherapy for bipolar disorder: A GBC survey

“…Insurance coverage is an issue in the United States; regular monitoring for Li, thyroid, and renal indices requires high copays and deductibles. The potential development of renal insufficiency 40,41 and thyroid dysfunction 42 are major concerns for Li nonprescription and even discontinuation by prescribers in the United States. 43 It is additionally possible that preference has been given to more recently approved treatments, such as SGAs and MSACs, and/or a perception of greater difficulty in using Li from the standpoint of laboratory drug monitoring and drug toxicity profile.…”

Thyroid hormone levels in patients with bipolar disorder: A systematic review and meta- analysis

“…Especially lithium therapists, it has proven to be the treatment of choice for BD, but its effect on thyroid function is explicit, due to the antithyroid effects of it, hypothyroidism is a common complication of it. [93,94]. What's more, supraphysiological doses of TH also appeared to be an excellent option for BD treatment [95,96].…”