Impact of Muscarinic M3 Receptor Antagonism on the Risk of Type 2 Diabetes in Antidepressant-Treated Patients: A Case-Controlled Study

Tran, Yen-Hao; Schuiling-Veninga, Catharina C M; Bergman, Jorieke E. H.; Groen, Henk; Wilffert, Bob

doi:10.1007/s40263-017-0436-x

Cited by 17 publications

(13 citation statements)

References 31 publications

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“…An inverse association between the inhibitory constant (Ki) for H 1 and prevalence of metabolic syndrome was also observed [6]. In addition, a case-control study suggested that antidepressants with antagonistic properties on M 3 are associated with incident type 2 diabetes [7]. A disproportionality analysis in the pharmacovigilance database of the WHO has also suggested that antidepressants might associate with diabetes, with a more pronounced risk for antidepressants with affinities to H 1 , 5-HT 2C and NET [5].…”

Section: Figurementioning

confidence: 92%

“…A recent pharmacoepidemiological-pharmacodynamic study in VigiBase suggested that antipsychotics with H 1 and 5-HT 2C antagonistic properties were associated with diabetes [4]. Similar receptor mechanisms could mediate antidepressant-induced metabolic side effects; in support, observational studies suggested that NET inhibition, as well as antagonism on 5-HT 2C , H 1 [5,6] and M 3 receptors [7], could explain the risk for diabetes.…”

Section: Introductionmentioning

confidence: 99%

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Detecting a potential safety signal of antidepressants and type 2 diabetes: a pharmacovigilance‐pharmacodynamic study

Siafis

Papazisis

2018

Brit J Clinical Pharma

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Section: Figurementioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Detecting a potential safety signal of antidepressants and type 2 diabetes: a pharmacovigilance‐pharmacodynamic study

Siafis

Papazisis

2018

Brit J Clinical Pharma

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“…Furthermore, doxepin-treated animals have been noted to have increased insulin sensitivity (IS); thus, doxepin may regulate glucose metabolism through Akt activation enhancement and gluconeogenesis suppression [ 28 , 29 ]. However, in patients using antipsychotics, doxepin can lead to hyperglycemia and exacerbate preexisting diabetes, hypertriglyceridemia, and hypercholesterolemia [ 30 , 31 , 32 ], but it can be an effective treatment option for postprandial hypoglycemia [ 33 ]. Long-term doxepin use can also induce NAFLD-associated body weight gain [ 34 ] and liver injury [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice

et al. 2021

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Doxepin is commonly prescribed for depression and anxiety treatment. Doxepin-related disruptions to metabolism and renal/hepatic adverse effects remain unclear; thus, the underlying mechanism of action warrants further research. Here, we investigated how doxepin affects lipid change, glucose homeostasis, chromium (Cr) distribution, renal impairment, liver damage, and fatty liver scores in C57BL6/J mice subjected to a high-fat diet and 5 mg/kg/day doxepin treatment for eight weeks. We noted that the treated mice had higher body, kidney, liver, retroperitoneal, and epididymal white adipose tissue weights; serum and liver triglyceride, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and creatinine levels; daily food efficiency; and liver lipid regulation marker expression. They also demonstrated exacerbated insulin resistance and glucose intolerance with lower Akt phosphorylation, GLUT4 expression, and renal damage as well as higher reactive oxygen species and interleukin 1 and lower catalase, superoxide dismutase, and glutathione peroxidase levels. The treated mice had a net-negative Cr balance due to increased urinary excretion, leading to Cr mobilization, delaying hyperglycemia recovery. Furthermore, they had considerably increased fatty liver scores, paralleling increases in adiponectin, FASN, PNPLA3, FABP4 mRNA, and SREBP1 mRNA levels. In conclusion, doxepin administration potentially worsens renal injury, nonalcoholic fatty liver disease, and diabetes.

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“…Prescription data from hospital and OTC drugs are not included in this database. The IADB.nl has been used as a reliable source of data for many pharmacoepidemiological researches …”

Section: Methodsmentioning

confidence: 99%

“…nl has been used as a reliable source of data for many pharmacoepidemiological researches. [19][20][21]…”

Section: Settingmentioning

confidence: 99%

Discontinuation and dose adjustment of metoprolol after metoprolol‐paroxetine/fluoxetine co‐prescription in Dutch elderly

Bahar

Wang

Bos

et al. 2018

Pharmacoepidemiology and Drug

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PurposeCo‐prescription of paroxetine/fluoxetine (a strong CYP2D6 inhibitor) in metoprolol (a CYP2D6 substrate) users is common, but data on the clinical consequences of this drug‐drug interaction are limited and inconclusive. Therefore, we assessed the effect of paroxetine/fluoxetine initiation on the existing treatment with metoprolol on the discontinuation and dose adjustment of metoprolol among elderly.MethodsWe performed a cohort study using the University of Groningen IADB.nl prescription database (www.IADB.nl). We selected all elderly (≥60 years) who had ever been prescribed metoprolol and had a first co‐prescription of paroxetine/fluoxetine, citalopram (weak CYP2D6 inhibitor), or mirtazapine (negative control) from 1994 to 2015. The exposure group was metoprolol and paroxetine/fluoxetine co‐prescription, and the other groups acted as controls. The outcomes were early discontinuation and dose adjustment of metoprolol. Logistic regression was applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).ResultsCombinations of metoprolol‐paroxetine/fluoxetine, metoprolol‐citalopram, and metoprolol‐mirtazapine were started in 528, 673, and 625 patients, respectively. Compared with metoprolol‐citalopram, metoprolol‐paroxetine/fluoxetine was not significantly associated with the early discontinuation and dose adjustment of metoprolol (OR = 1.07, 95% CI:0.77‐1.48; OR = 0.87, 95% CI:0.57‐1.33, respectively). In comparison with metoprolol‐mirtazapine, metoprolol‐paroxetine/fluoxetine was associated with a significant 43% relative increase in early discontinuation of metoprolol (OR = 1.43, 95% CI:1.01‐2.02) but no difference in the risk of dose adjustment. Stratified analysis by gender showed that women have a significantly high risk of metoprolol early discontinuation (OR = 1.62, 95% CI:1.03‐2.53).ConclusionParoxetine/fluoxetine initiation in metoprolol prescriptions, especially for female older patients, is associated with the risk of early discontinuation of metoprolol.

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Impact of Muscarinic M3 Receptor Antagonism on the Risk of Type 2 Diabetes in Antidepressant-Treated Patients: A Case-Controlled Study

Cited by 17 publications

References 31 publications

Detecting a potential safety signal of antidepressants and type 2 diabetes: a pharmacovigilance‐pharmacodynamic study

Detecting a potential safety signal of antidepressants and type 2 diabetes: a pharmacovigilance‐pharmacodynamic study

Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice

Discontinuation and dose adjustment of metoprolol after metoprolol‐paroxetine/fluoxetine co‐prescription in Dutch elderly

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