TY - JOUR

T1 - Pharmacological treatment of bipolar disorder and risk of diabetes mellitus

T2 - A nationwide study of 30,451 patients

AU - Rohde, Christopher

AU - Köhler-Forsberg, Ole

AU - Nierenberg, Andrew A

AU - Østergaard, Søren Dinesen

N1 - This article is protected by copyright. All rights reserved.

PY - 2023/6

Y1 - 2023/6

N2 - Objective: While treatment 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. The aim of this study was 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. Methods: Using nationwide registers, we 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, we 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. Results: During follow-up (245,181 person-years), 2107 (6.9%) patients developed DM. Compared with non-users of the respective drugs, we found no clinically or statistically significant difference in the risk of developing DM 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. For antipsychotics, we observed a clear cumulative dose–response-like association with the risk of DM. Conclusions: 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.

AB - Objective: While treatment 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. The aim of this study was 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. Methods: Using nationwide registers, we 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, we 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. Results: During follow-up (245,181 person-years), 2107 (6.9%) patients developed DM. Compared with non-users of the respective drugs, we found no clinically or statistically significant difference in the risk of developing DM 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. For antipsychotics, we observed a clear cumulative dose–response-like association with the risk of DM. Conclusions: 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.

KW - anticonvulsants

KW - antipsychotic agents

KW - bipolar disorder

KW - diabetes mellitus

KW - lamotrigine

KW - lithium

KW - valproic acid

KW - Diabetes Mellitus/chemically induced

KW - Lamotrigine/adverse effects

KW - Lithium/therapeutic use

KW - Humans

KW - Bipolar Disorder/drug therapy

KW - Antimanic Agents/adverse effects

KW - Anticonvulsants/adverse effects

KW - Antipsychotic Agents/adverse effects

KW - Valproic Acid/adverse effects

U2 - 10.1111/bdi.13308

DO - 10.1111/bdi.13308

M3 - Journal article

C2 - 36751986

VL - 25

SP - 323

EP - 334

JO - Bipolar disorders

JF - Bipolar disorders

SN - 1399-5618

IS - 4

ER -