Metformin Enhances Antidepressant/Antipsychotic Combination Therapy of Schizophrenia With Comorbid Depression in a Murine Model

Zhou, Chunhua; Kong, Dezhi; Xue, Rong; Chen, Min; Li, Gongying; Xu, Yong; Li, Sha; Tian, Hongjun; Zhuo, Chuanjun

doi:10.3389/fnins.2020.00517

Cited by 9 publications

(8 citation statements)

References 43 publications

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“…Through the analysis of reports of various types and the time of occurrence of DILI caused by different dosage forms of aripiprazole, we found that the time of occurrence in all cases was from 15 to 90 days (about 67.92% of the time) after continuous usage. This may be related to the fact that most of the clinical increases in the dose of this drug were done incrementally after 2 weeks of administration, and it may also be related to the length of the course of drug administration ( Zhou et al, 2020 ). In terms of recovery, 78.76% of patients improved or recovered after discontinuation of aripiprazole or suitable treatment, and this finding was consistent with the ease of recovery from the effects of aripiprazole on liver function that is reported in literature ( Wang et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Aripiprazole-induced liver injury: a spontaneous reporting database study

Gao,

Wu,

Zhai

et al. 2023

Front. Pharmacol.

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Background: There have been individual case reports of aripiprazole in recent years, both domestically and internationally, but no analysis of the characteristics of the occurrence of adverse reactions/events of drug-induced liver injury with aripiprazole using spontaneous reports has been seen.Methods: Using a retrospective study approach, the 452 adverse reaction/event reports of aripiprazole-induced liver injury collected by the China Adverse Drug Reaction Monitoring System from 1 January 2012 to 31 December 2016 were analyzed and evaluated, and exploring it’s the clinical characteristics and related risk factors for liver injury occurrence.Results: Among 452 cases of aripiprazole-induced liver injury ADR/ADE reports, there were 121 cases classified as serious, accounting for 26.8% of the total. There were 250 male and 202 female patients, with a male-to-female ratio of 1.24:1. The age of patients ranged from 11 to 77 years old, with an average age of (34.56 ± 12.81) years old, and a high proportion of young adults in the total population. Some patients had used the drug off-label or at a higher than recommended dosage. The onset of liver injury was generally within 15–90 days after continuous use, while some patients are also accompanied by nausea, vomiting, and weight gain. 70% of the combined drug instructions listed that may cause liver injury.Conclusion: In clinical practice, healthcare professionals should pay closely attention to the adverse reactions and risk factors of liver injury caused by aripiprazole. If there are potential risk factors for liver injury, early and regular monitoring of liver function should be carried out to reduce the occurrence of adverse reactions.

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Section: Discussionmentioning

confidence: 99%

Aripiprazole-induced liver injury: a spontaneous reporting database study

Gao,

Wu,

Zhai

et al. 2023

Front. Pharmacol.

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“…Quality of life and depressive symptomatology revealed no significant differences between the two study groups ( Supplementary Table 1 ). However, metformin showed antidepressant effects in larger cohorts and animal models ( 8 , 32 ), and was even shown to correct abnormal circadian rhythm on a cellular level via an activation of AMPK ( 33 ). Mechanistically, the action of metformin is not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

Metformin and Bone Metabolism in Endogenous Glucocorticoid Excess: An Exploratory Study

et al. 2021

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ContextGlucocorticoid excess exhibits multiple detrimental effects by its catabolic properties. Metformin was recently suggested to protect from adverse metabolic side-effects of glucocorticoid treatment. Whether metformin is beneficial in patients with endogenous glucocorticoid excess has not been clarified.ObjectiveTo evaluate the phenotype in patients with endogenous Cushing’s syndrome (CS) treated with metformin at the time of diagnosis.Patients and MethodsAs part of the German Cushing’s Registry we selected from our prospective cohort of 96 patients all 10 patients who had been on pre-existing metformin treatment at time of diagnosis (CS-MET). These 10 patients were matched for age, sex and BMI with 16 patients without metformin treatment (CS-NOMET). All patients had florid CS at time of diagnosis. We analyzed body composition, metabolic parameters, bone mineral density and bone remodeling markers, muscle function and quality of life.ResultsAs expected, diabetes was more prevalent in the CS-MET group, and HbA1c was higher. In terms of comorbidities and the degree of hypercortisolism, the two groups were comparable. We did not observe differences in terms of muscle function or body composition. In contrast, bone mineral density in metformin-treated patients was superior to the CS-NOMET group at time of diagnosis (median T-Score -0.8 versus -1.4, p = 0.030). CS-MET patients showed decreased β-CTX levels at baseline (p = 0.041), suggesting reduced bone resorption under metformin treatment during glucocorticoid excess.ConclusionThis retrospective cohort study supports potential protective effects of metformin in patients with endogenous glucocorticoid excess, in particular on bone metabolism.

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“…Data were compared using one-way analysis of variance and post hoc Tukey tests. Data analysis and figure plotting were performed with the GraphPad Prism software (version 8.0) [ 65 , 66 ]. No animals were excluded from the present study.…”

Section: Methodsmentioning

confidence: 99%

Calcium imaging reveals depressive- and manic-phase-specific brain neural activity patterns in a murine model of bipolar disorder: a pilot study

et al. 2021

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Brain pathological features during manic/hypomanic and depressive episodes in the same patients with bipolar disorder (BPD) have not been described precisely. The study aimed to investigate depressive and manic-phase-specific brain neural activity patterns of BPD in the same murine model to provide information guiding investigation of the mechanism of phase switching and tailored prevention and treatment for patients with BPD. In vivo two-photon imaging was used to observe brain activity alterations in the depressive and manic phases in the same murine model of BPD. Two-photon imaging showed significantly reduced Ca2+ activity in temporal cortex pyramidal neurons in the depression phase in mice exposed to chronic unpredictable mild stress (CUMS), but not in the manic phase in mice exposed to CUMS and ketamine. Total integrated calcium values correlated significantly with immobility times. Brain Ca2+ hypoactivity was observed in the depression and manic phases in the same mice exposed to CUMS and ketamine relative to naïve controls. The novel object recognition preference ratio correlated negatively with the immobility time in the depression phase and the total distance traveled in the manic phase. With recognition of its limitations, this study revealed brain neural activity impairment indicating that intrinsic emotional network disturbance is a mechanism of BPD and that brain neural activity is associated with cognitive impairment in the depressive and manic phases of this disorder. These findings are consistent with those from macro-imaging studies of patients with BPD. The observed correlation of brain neural activity with the severity of depressive, but not manic, symptoms need to be investigated further.

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Metformin Enhances Antidepressant/Antipsychotic Combination Therapy of Schizophrenia With Comorbid Depression in a Murine Model

Cited by 9 publications

References 43 publications

Aripiprazole-induced liver injury: a spontaneous reporting database study

Aripiprazole-induced liver injury: a spontaneous reporting database study

Metformin and Bone Metabolism in Endogenous Glucocorticoid Excess: An Exploratory Study

Calcium imaging reveals depressive- and manic-phase-specific brain neural activity patterns in a murine model of bipolar disorder: a pilot study

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