Cardiometabolic risk markers during mood-stabilizing treatment: Correlation with drug-specific effects, depressive symptoms and treatment response

Kuperberg, Maya; Köhler‐Forsberg, Ole; Shannon, Alec P.; George, Nevita; Greenebaum, Sophie; Bowden, Charles L.; Calabrese, Joseph R.; Thase, Michael E.; Shelton, Richard C.; McInnis, Melvin G.; Deckersbach, Thilo; Tohen, Mauricio; Kocsis, James H.; Ketter, Terence A.; Friedman, Edward S.; Iosifescu, Dan V.; Ostacher, Michael J.; Sylvia, Louisa G.; McElroy, Susan L.; Nierenberg, Andrew A.

doi:10.1016/j.jad.2021.12.047

Cited by 9 publications

(10 citation statements)

References 34 publications

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“…12 These data, however, stem from RCTs with relatively short follow-up periods, participants who met strict inclusion and exclusion criteria, and there are less data on the risk of DM associated with antipsychotic treatment of bipolar disorder from naturalistic clinical settings. 4,[13][14][15][16] While the increased risk of DM with antipsychotics is rather well established, it is less clear how lithium-a widely used mood stabilizer in the treatment of bipolar disorder 12,17 -affects the risk of DM. While there were initial concerns of increased risk of DM with lithium treatment, 18,19 studies have generally suggested either no effect 14,18 or even a protective effect of lithium on the risk of DM.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological treatment of bipolar disorder and risk of diabetes mellitus: A nationwide study of 30,451 patients

et al. 2023

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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.

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Section: Introductionmentioning

confidence: 99%

Pharmacological treatment of bipolar disorder and risk of diabetes mellitus: A nationwide study of 30,451 patients

et al. 2023

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“…Several other studies have found low HDL-C levels to be a predictor of the severity of depressive symptoms in patients with FEDN MDD ( 31 ). A positive correlation between TC and LDL-C levels and the severity of depressive symptoms has also been reported ( 32 ). In the general population, low HDL-C levels are found to be associated with the development of depressive symptoms ( 33 ), while in the general middle-aged population, high HDL-C levels or high TC levels are found to be risk factors for the development of depressive symptoms ( 34 – 36 ).…”

Section: Discussionmentioning

confidence: 90%

Association of thyroid function with abnormal lipid metabolism in young patients with first-episode and drug naïve major depressive disorder

Ji²,

Lang³

et al. 2023

Front. Psychiatry

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IntroductionAbnormal lipid metabolism in patients with major depressive disorder (MDD) has received increasing attention. The coexistence of MDD and abnormal thyroid function has been intensively studied. Moreover, thyroid function is closely related to lipid metabolism. The aim of this study was to investigate the relationship between thyroid function and abnormal lipid metabolism in young patients with first-episode and drug naïve (FEDN) MDD.MethodsA total of 1,251 outpatients aged 18–44 years with FEDN MDD were enrolled. Demographic data were collected, and lipid and thyroid function levels were measured, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free tetraiodothyronine (FT4), anti-thyroglobulin antibody (TG-Ab), and anti-thyroid peroxidase antibody (TPO-Ab). The Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Rating Scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) positive subscale were also assessed for each patient.ResultsCompared with young MDD patients without comorbid lipid metabolism abnormalities, patients with comorbid lipid metabolism abnormalities had higher body mass index (BMI) values, HAMD score, HAMA score, PANSS positive subscale score, TSH levels, TG-Ab levels, and TPO-Ab levels. Binary logistic regression analysis showed that TSH level, HAMD score and BMI were risk factors for abnormal lipid metabolism. TSH levels were an independent risk factor for abnormal lipid metabolism in young MDD patients. Stepwise multiple linear regression showed that both TC and LDL-C levels were positively correlated with TSH levels, HAMD and PANSS positive subscale scores, respectively. HDL-C levels were negatively correlated with TSH levels. TG levels were positively correlated with TSH and TG-Ab levels and HAMD score.DiscussionOur results show that thyroid function parameters, especially TSH levels, are implicated in abnormal lipid metabolism in young patients with FEDN MDD.

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“…Findings indicating that it plays a crucial role hippocampal neuron development and survival suggest that regulation of GSK3β could be a clinical target for neuropsychiatric disorders, such as depression and anxiety disorders [ 1 , 4 ]. Indeed GSK-3β-actuated molecular cascades have been reported to have modulatory influences on depression and anxiety disorders [ 5 – 7 ]. Notably, regulation of GSK3β has been implicated in antidepressant mechanisms of action and in the pathogenesis of depression [ 8 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…For nearly a century, lithium (Li) has been widely used to treat acute depression, acute mania, and treatment-resistant depression [ 1 – 4 ]. A number of randomized controlled trials support the primary use of Li as a mood stabilizer in the maintenance care of patients with bipolar disorder (BP) [ 5 – 10 ]. The American Psychiatric Association (APA) [ 11 ] recommends Li to prevent manic, hypomanic, and mixed episodes and has described Li as a ‘traditional’ mood stabilizer, as opposed to the ‘new’ mood stabilizers, also known as second-generation antipsychotics, such as olanzapine, risperidone, ziprasidone, quetiapine, and aripiprazole [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Lithium produces bi-directionally regulation of mood disturbance, acts synergistically with anti-depressive/-manic agents, and did not deteriorate the cognitive impairment in murine model of bipolar disorder

et al. 2022

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Lithium (Li) is a well-established mood disorder treatment and may be neuroprotective. Bi-directional regulation (i.e. affecting manic symptoms and depressive symptoms) by Li has not been demonstrated. This study explored: (1) bidirectional regulation by Li in murine models of depression, mania, and bipolar disorder (BP); and (2) potential Li synergism with antidepressant/anti-mania agents. The chronic unpredictable mild stress (CUMS) and ketamine-induced mania (KM) models were used. These methods were used in series to produce a BP model. In vivo two-photon imaging was used to visualize Ca2+ activity in the dorsolateral prefrontal cortex. Depressiveness, mania, and cognitive function were assessed with the forced swim task (FST), open field activity (OFA) task, and novel object recognition task, respectively. In CUMS mice, Ca2+ activity was increased strongly by Li and weakly by lamotrigine (LTG) or valproate (VPA), and LTG co-administration reduced Li and VPA monotherapy effects; depressive immobility in the FST was attenuated by Li or LTG, and attenuated more strongly by LTG-VPA or LTG-Li; novel object exploration was increased strongly by Li and weakly by LTG-Li, and reduced by LTG, VPA, or LTG-VPA. In KM mice, Li or VPA attenuated OFA mania symptoms and normalized Ca2+ activity partially; Li improved cognitive function while VPA exacerbated the KM alteration. These patterns were replicated in the respective BP model phases. Lithium had bi-directional, albeit weak, mood regulation effects and a cognitive supporting effect. Li co-administration with antidepressant/-manic agents enhanced mood-regulatory efficacy while attenuating their cognitive-impairing effects.

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Cardiometabolic risk markers during mood-stabilizing treatment: Correlation with drug-specific effects, depressive symptoms and treatment response

Cited by 9 publications

References 34 publications

Pharmacological treatment of bipolar disorder and risk of diabetes mellitus: A nationwide study of 30,451 patients

Pharmacological treatment of bipolar disorder and risk of diabetes mellitus: A nationwide study of 30,451 patients

Association of thyroid function with abnormal lipid metabolism in young patients with first-episode and drug naïve major depressive disorder

Lithium produces bi-directionally regulation of mood disturbance, acts synergistically with anti-depressive/-manic agents, and did not deteriorate the cognitive impairment in murine model of bipolar disorder

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