Treatment of bipolar disorder with valproate and antipsychotics linked to risk of diabetes mellitus

Bipolar disorder is a severe mental disorder with high comorbidity with diabetes mellitus (DM). Specifically, the prevalence of diabetes among individuals with bipolar disorder is estimated to be 9%–11%, corresponding to approximately twice the risk of DM in the general population.

Researcher Christopher Rohde and team aimed to investigate whether treatment of bipolar disorder with lithium, antipsychotics, or antiepileptics is associated with the risk of DM in a real-world clinical setting. The study is published in International journal of Psychiatry and Neurosciences.

Bipolar disorder commonly treated with antipsychotics and antiepileptics have been associated with an increased risk of diabetes mellitus (DM), lithium may have the opposite effect via inhibition of glycogen synthase kinase-3, however valproate and antipsychotics was associated with increased risk of DM in a real-world cohort of patients with bipolar disorder than lithium.

The nationwide study, identified all patients diagnosed with bipolar disorder in Danish Psychiatric Services from January 1, 1996, to January 1, 2019 (N = 30,451). The risk of developing DM was operationalized via hospital diagnoses and redeemed prescriptions for glucose-lowering drugs. For lithium, antipsychotics, valproate, and lamotrigine, they calculated hazard rate ratios (HRR) for developing DM via adjusted Cox proportional hazards models. Potential cumulative dose–response-like associations were examined using the log-rank test.

The key findings of the study are

• During follow-up (245,181 person-years), 2107 (6.9%) patients developed DM. Compared with non-users of the respective drugs, no clinically or statistically significant difference in the risk of developing DM was found.

• Among patients receiving lithium (n = 11,690; incidence rate of DM/1000 person-years (IR) = 8.87, 95% CI: 8.02–9.90; HRR = 0.94, 95% CI: 0.84–1.06) or lamotrigine (n = 11,785; IR = 7.58, 95% CI: 6.69–8.59; HRR = 0.89, 95% CI: 0.77–1.02), respectively.

• Conversely, for patients receiving valproate (n = 5171; IR = 12.68, 95% CI: 10.87–14.80; HRR = 1.34, 95% CI: 1.14–1.58) and antipsychotics (n = 22,719; IR = 12.00, 95% CI: 11.14–12.94; HRR = 1.65, 95% CI: 1.45–1.88) respectively, there was increased risk of developing DM.

The researchers concluded that “treatment with valproate and antipsychotics—but not with lithium and lamotrigine—was associated with increased risk of DM in a real-world cohort of patients with bipolar disorder.”

Reference: Christopher Rohde, Ole Köhler-Forsberg, et al, Pharmacological treatment of bipolar disorder and risk of diabetes mellitus: A nationwide study of 30,451 patients; https://doi.org/10.1111/bdi.13308.