Effects of Impaired Glucose Metabolism on Lithium and Other Mood Stabilizers

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Patients with bipolar disorder and type 2 diabetes may not respond well to mood stabilizing treatments, such as lithium.
Patients with bipolar disorder and type 2 diabetes may not respond well to mood stabilizing treatments, such as lithium.

Impaired glucose metabolism may affect response to lithium and other mood stabilizer treatments among patients with bipolar disorder (BD), according to study data published in the Journal of Affective Disorders.

Patients with BD who had been receiving mood stabilizer treatment for at least 1 year (n=91) were enrolled in the trial. Patients with insulin resistance or type 2 diabetes (n=45) were compared with patients who had normal glucose metabolism (n=46). As a primary outcome measure, researchers evaluated between-group differences in mood stabilizer treatment response per the retrospective criteria of long-term treatment response in BD (the Alda scale). Treatment responses were categorized by Alda score as poor (≤3), moderate (4-6), and good (≥7). Patients were also assessed for illness severity, global functioning, depressive and anxiety symptoms, and the presence of manic symptoms. An ordinal logistic regression model was constructed to identify which clinical characteristics were predictive of response to mood stabilizer treatments.

The study cohort was composed of 63 (69.2%) patients with BD type I and 28 (30.8%) patients with BD type II. Among patients receiving lithium monotherapy (n=17), 41% had impaired glucose metabolism. In patients treated with lithium in combination with other mood stabilizers (n=16), valproic acid monotherapy (n=43), lamotrigine monotherapy (n=12), or carbamazepine monotherapy (n=3), the proportion of individuals with glucose dysregulation were 44%, 51%, 58%, and 67%, respectively.

Compared with patients with normal glucose metabolism, patients with impaired glucose metabolism were older at study entry (P <.001) and at first psychiatric contact (P <.006), although they reported younger age at illness onset (P <.034). Patents with impaired metabolism also had a higher body mass index (P <.0001) and higher mean fasting plasma triglycerides levels (P <.017). In addition, 53% of patients in the dysmetabolic group were classified as obese compared with just 11% of the normal metabolic group.

According to the Alda scale, 20 patients experienced a good response to mood stabilizers, 42 experienced a moderate response, and 29 experienced a poor response. The impaired metabolism group had significantly fewer patients with good treatment responses (P <.012) compared with the unimpaired metabolism group. Per ordinal regression analysis, using ALDA scale response as the referent, none of the sociodemographic or clinical variables were risk factors for poor mood stabilizer response. Instead, impaired glucose metabolism emerged as a significant predictor of poor response to mood stabilizers (P <.001).

These findings expand on prior literature that identified glucose dysregulation as a risk factor for poor response to lithium and other mood stabilizer treatments. Future research is needed to parse the precise risk factors for poor response according to mood stabilizer type, as each is metabolized in different ways.

Reference

Fabrazzo M. Impaired glucose metabolism in bipolar patients and response to mood stabilizer treatments. J Affect Disord. 2018;245:174-179.

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