Trip Answers

Question answered:12/10/06 Warning! this question is over two years old.

We identified two British guidelines on bipolar disorder which discuss lithium therapy, neither of which specifically mention calcium levels should be monitored [1-2]. The NICE guideline, published in July 2006, notes in section 1.6.2.10:

 

“Monitor serum lithium levels normally every 3 months.
• Monitor older adults carefully for symptoms of lithium toxicity, because they may develop high serum levels of lithium at doses in the normal range, and lithium toxicity is possible at moderate serum lithium levels.
• Monitor weight, especially in patients with rapid weight gain.
• Undertake more frequent tests if there is evidence of clinical deterioration, abnormal results, a change in sodium intake, or symptoms suggesting abnormal renal or thyroid function such as unexplained fatigue, or other risk factors, for example, if the patient is starting medication such as ACE inhibitors, non-steroidal anti-inflammatory drugs, or diuretics.
• Arrange thyroid and renal function tests every 6 months, and more often if there is evidence of impaired renal function.” [1]

 

However, a document on drug monitoring produced by the Dyfed Powys Primary Care Effectiveness team advises that serum calcium levels be checked annually in patients prescribed lithium (see Page 9). [3]

 

A search conducted in the TRIP (www.tripdatabase.com) and Medline databases identified a number of reviews suggesting a need for monitoring serum calcium levels in patients taking lithium.

 

A review article on lithium-induced hypercalcemia and parathyroid function notes:

 

“Currently, there is no consensus on the prevalence, severity, or exact mechanism underlying lithium-induced hypercalcemia and parathyroid dysfunction.

 

Total serum calcium, serum proteins, and ionized calcium are usually sufficient to exclude any abnormalities before lithium is instituted. Periodic monitoring of serum calcium levels during lithium therapy is warranted. Hypercalcemia should be considered in any patient who becomes delirious or who develops any of the symptoms noted above. Hypercalcemia should also be considered in any patient who becomes refractory to lithium after an initial response. Any patient who is noted to be hypercalcemic or to have hyperparathyroidism prior to initiation of mood stabilizer therapy should not receive lithium, and patients who develop lithium-induced parathyroid dysfunction should be switched to an alternate mood stabilizer. After discontinuation of lithium therapy, PTH levels may remain elevated for months but in most cases the hyperparathyroid state is reversible and should not prompt premature surgical intervention.” [4]

 

Khandwala and Van Umm presented a case report and literature review of reversible hypercalcaemia and hyperparathyroidism, from which they conclude:

 

“Hypercalcemia associated with lithium-induced hyperparathyroidism is a common, but underrecognized, complication of lithium therapy. Most patients have mild asymptomatic hypercalcemia. The long-term consequences of mild lithium-induced hypercalcemia are unknown. After discontinuation of lithium, the hypercalcemia may not always resolve; thus, parathyroidectomy may be necessary in some cases. Measurement of the serum calcium and PTH levels before and periodically after the initiation of lithium treatment is advisable. The appropriate monitoring of patients with lithium-induced hypercalcemia and decisions regarding parathyroidectomy are unclear. The decision to continue lithium therapy in the presence of hypercalcemia should be individualized.” [5]

 

Finally, Livingstone and Rampes note in a review article discussing the metabolic adverse effects of lithium:

 

“The serum calcium level should be checked before commencing treatment with lithium and 6 monthly thereafter. If the calcium level is noted to be elevated, PTH should be measured and interpreted relative to the ambient serum calcium concentration.
Lithium levels should also be monitored closely as hypercalcaemia is likely to be worse if lithium levels are toxic and adversely influencing renal function. If a patient is found to have symptomatic primary hyperparathyroidism on baseline screening, lithium treatment should be avoided.” [6]

 

References
1. NICE. Bipolar disorder: the management of bipolar disorder in adults, children and adolescents, in primary and secondary care. July 2006. (http://www.nice.org.uk/download.aspx?o=cg38niceguideline).
2. SIGN. Bipolar affective disorder. 2005. (http://www.sign.ac.uk/pdf/sign82.pdf).
3. Dyfed Powys Primary Care Effectiveness Team. Drug monitoring: a risk assessment system. 2004. (http://www.wales.nhs.uk/sites/documents/368/Drug%20Monitoring%20Leaves.pdf).
4. Rifai M, Moles J and Harrington D. Lithium-induced hypercalcemia and parathyroid dysfunction. Psychosomatics. 2001 Jul-Aug;42(4):359-61. (http://psy.psychiatryonline.org/cgi/content/full/42/4/359).
5. Khandwala HM, Van Uum S. Reversible hypercalcemia and hyperparathyroidism associated with lithium therapy: case report and review of literature. Endocr Pract. 2006 Jan-Feb;12(1):54-8. (
6. Livingstone C and Rampes H. Lithium: a review of metabolic adverse effects. Journal of Psychopharmacology 2006;20(3):347-355. (http://jop.sagepub.com/cgi/reprint/20/3/347.pdf#search=%22monitoring%20calcium%20levels%20in%20patients%20on%20lithium%22. 

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