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Valproate tied to highest risk of T2DM in adults versus other anticonvulsant mood stabilizers

JAMA Network Open
Reuters Health -  14/04/2022 - Among anticonvulsant mood stabilizers, valproate is associated with the highest risk of developing type 2 diabetes mellitus (T2DM) in adults, whereas lamotrigine conferred the lowest risk, a cohort study suggests. 

Anticonvulsant mood stabilizers are widely used by adults and children for the treatment of epilepsy, bipolar disorder, and neuropathic pain. 

"The most surprising takeaway is that metabolic risk could be an important consideration to weigh when starting treatment," Dr. Jenny Sun of Harvard Medical School and Harvard Pilgrim Health Care Institute in Boston told Reuters Health by email. "Metabolic risk is often a less known risk factor of treatment, but its potential effects can have a long-lasting impact on patients." 

Overall, she said, "Valproate treatment was associated with a small increased risk of developing T2D compared to other anticonvulsant mood stabilizers in adults. Findings were similar in children, but few developed T2D." 

"Patients or providers concerned about potential metabolic risks of treatment could consider choosing lamotrigine after weighing the other known risks and benefits of anticonvulsant mood stabilizer treatment," she advised. 

As reported in JAMA Network Open, Dr. Sun and colleagues analyzed medical record data for close to 275,000 adults (mean age, 40; 58%, women) and 74,000 children (mean age, 15.6; 52%, girls) who initiated an anticonvulsant mood stabilizer. 

In adults, taking valproate was associated with an increased risk of developing T2D compared with lamotrigine (5-year risk difference, 1.17%). The number needed to harm was 87 patients initiating valproate for one to develop T2D during follow-up, compared with initiation of lamotrigine. 

Point estimates were similar when assessing the association of treatment continuation (5-year RD, 1.99%). The estimated association was smaller and more variable in comparisons of carbamazepine and oxcarbazepine to lamotrigine. 

In children, RDs were much smaller and more variable: 5-year RD for initiation of oxcarbazepine versus lamotrigine, 0.29% and 0.18% for initiation of valproate versus lamotrigine. 

The authors write, "In the absence of randomized trials, emulating target trials within health care databases can generate the age-specific drug safety data needed to inform treatment decision-making." 

Dr. Zachary Freyberg, an assistant professor of psychiatry at the Center for Neuroscience at the University of Pittsburgh, told Reuters Health by email that the findings are "consistent with my own clinical experiences, where anticonvulsant medications such as valproate produce weight gain and, over time, increase likelihood of impairments in blood sugar control, ultimately raising the risk for development of T2D." 

One concern about the study, in addition to its observational nature, he said, "is the high degree of psychiatric comorbidity in the subjects taking the anticonvulsant medications. There is increasing evidence that psychiatric illnesses such as bipolar disorder and schizophrenia, on their own, have a heightened risk of type 2 diabetes and impaired blood sugar control." 

Further, he said, "Most of the antipsychotic medications used to treat many of these psychiatric illnesses can cause weight gain and raise diabetes risk. Addition of anticonvulsant medications, when placed against this background of increased intrinsic metabolic risk and preexisting medications that themselves raise diabetes risk, creates a complex picture, where it becomes potentially difficult to accurately disentangle the respective contributions of all these factors to the development of T2D." 

Nonetheless, he said, "Physicians should be aware of the metabolic side effects of these medications. This may be especially important to take into consideration if the individuals treated with these medications already have diabetes or other conditions predisposing them to developing T2D." 

SOURCE: https://bit.ly/3jDcigT  JAMA Network Open, online April 6, 2022. 

By Marilynn Larkin 

© 2023 The Author(s). Published by Medicom Medical Publishers.
User license: Creative Commons Attribution – NonCommercial (CC BY-NC 4.0)

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