Atorvastatin lowers serum calcium levels in lithium-users: results from a randomized controlled trial

Abstract

Background Although lithium is considered the gold-standard treatment for bipolar disorder (BD), it is associated with a variety of major endocrine and metabolic side effects, including parathyroid hormone (PTH) dependent hypercalcemia. Aside from surgery and medication discontinuation, there are limited treatments for hypercalcemia. This paper will assess data from a randomized controlled trial (RCT). Methods This is a secondary analysis of an RCT that explored the effects of atorvastatin (n = 27) versus placebo (n = 33) on lithium-induced nephrogenic diabetes insipidus (NDI) in patients with BD and major depressive disorder (MDD) using lithium (n = 60), over a 12-week period. This secondary analysis will explore serum calcium levels and thyroid stimulating hormone (TSH) measured at baseline, week 4, and week 12. Results At 12-weeks follow-up while adjusting results for baseline, linear regression analyses found that corrected serum calcium levels were significantly lower in the treatment group (mean (M) = 2.30 mmol/L, standard deviation (SD) = 0.07) compared to the placebo group (M = 2.33 mmol/L, SD = 0.07) (β = − 0.03 (95% C.I.; − 0.0662, − 0.0035), p = 0.03) for lithium users. There were no significant changes in TSH. Conclusion In lithium users with relatively normal calcium levels, receiving atorvastatin was associated with a decrease in serum calcium levels. Although exciting, this is a preliminary finding that needs further investigation with hypercalcemic patients. Future RCTs could examine whether atorvastatin can treat PTH dependent hypercalcemia due to lithium and other causes.

Cross‐sectional association between blood cholesterol and calcium levels in genetically diverse strains of mice

“…In terms of whether cholesterol could be driving hypercalcemia, there is some evidence. Two interventional studies using statins have shown reductions in calcium levels [ 49 , 50 ], whereas another single‐arm study showed declines that did not reach significance [ 51 ]. A Mendelian Randomization approach using LDL‐C as the instrument was also associated with elevated calcium levels [ 52 ], further supporting a potential causal relationship with cholesterol driving calcium levels.…”

Cross-sectional association between blood cholesterol and calcium levels in genetically diverse strains of mice

“…In terms of whether cholesterol could be driving hypercalcemia, there is some positive evidence. Two interventional studies using statins have showed a reductions in calcium levels [45,46], whereas another single-arm study showed declines that did not reach significance [47] . A Mendelian Randomization approach using LDL-C as the instrument was also associated with elevated calcium levels [48], further supporting a potential causal relationship with cholesterol driving calcium levels.…”

Diabetes Insipidus: Types, Diagnosis and Management

“…Lithium therapy might lead to difficulties if it is used for an extended period. Even when lithium therapy has been stopped, prolonged lithium administration can cause irreversible nephrogenic diabetic insipidus [33,34]. The administration of DDAVP is ineffective because the primary problem is a nephron's insensitivity to ADH rather than a lack of ADH release [35].…”