Amato D, Vernon AC, Papaleo F. Dopamine, the antipsychotic molecule: a perspective on mechanisms underlying antipsychotic response variability. Bethesda, MD 20894, Web Policies 2011;11:197. Mol Psychiatry. Below, check out the tour dates, as well as a weird tour . Higher antipsychotic doses are associated with a higher risk of diabetes. Joffe G, Takala P, Tchoukhine E, Hakko H, Raidma M, Putkonen H, et al. Antipsychotics play an essential part of the management of people with severe mental illness; however, this comes at the cost of an increased risk of weight gain and, for a minority, diabetes. Again, the effects of these drugs on the risk of diabetes in people taking antipsychotics have not been studied but a meta-analysis of 12 studies involving 743 people treated with antipsychotics showed that metformin lead to a mean 3.3-kg reduction in body weight over 36months. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). The relative risks for diabetes appear to be higher in adolescents and young adults. In five cases, the same antipsychotic was re-started after recovery with subsequent hyperglycaemia in four cases. Vancampfort D, Wampers M, Mitchell AJ, Correll CU, De Herdt A, Probst M, et al. Diabetologia. The potential mechanisms by which antipsychotics are associated with an increased risk of, MeSH Antipsychotics may further worsen weight gain by reducing energy expenditure. 2006;49(7):146776. Association Between Antipsychotic Medication Use and Diabetes Richard I. G. Holt 1,2 Author information Copyright and License information This article has been cited by other articles in PMC. Deng C. Effects of antipsychotic medications on appetite, weight, and insulin resistance. The reported risk ratios are highly variable ranging up to a 33-fold increase but often with wide confidence intervals; however, typically the relative risks are less than two [12]. As genetics, environmental and disease-specific effects may all contribute to the increased risk of diabetes in people with psychosis, it is difficult to assess the degree, if any, to which an antipsychotic has contributed to hyperglycaemia [9]. While the risk of developing diabetes-related microvascular complications is higher in people taking antipsychotic medication, it is unknown whether this differs between antipsychotics [20]. Part of Springer Nature. Obesity, serious mental illness and antipsychotic drugs. BMC Psychiatry. These drugs are highly obesogenic drugs and more than 7% weight gain occurs in 1572% of people taking second-generation antipsychotics [30]. Front Neurosci. Granger B, Albu S. The haloperidol story. An association between antipsychotic medication and diabetes mellitus and/or impaired glucose tolerance was reported in the 1950s, soon after chlorpromazine entered clinical practice (Reference Hiles Hiles, 1956).Other reports followed (e.g. In common with the first-generation antipsychotics, they have variable effects on muscarinic, histamine and adrenergic receptors. Joffe G, Takala P, Tchoukhine E, Hakko H, Raidma M, Putkonen H, et al. The risk of type 2 diabetes increases markedly with increasing weight and body mass index with obesity accounting for 8085% of the overall risk of type 2 diabetes. Chronic kidney disease and severe mental illness: a scoping review. Over the last decade, the gut microbiome has been identified as an important factor in the pathogenesis of obesity and other metabolic diseases. Crawford MJ, Jayakumar S, Lemmey SJ, Zalewska K, Patel MX, Cooper SJ, et al. Antipsychotic drugs and diabetes--an application of the Austin Bradford Hill criteria. Vancampfort D, Correll CU, Galling B, Probst M, De Hert M, Ward PB, et al. Kessing LV, Thomsen AF, Mogensen UB, Andersen PK. The prevalence of diabetes is ~10% among people taking antipsychotics, which is 23-fold higher than the general population [1, 2]. Yood MU, DeLorenze G, Quesenberry CP Jr, Oliveria SA, Tsai AL, Willey VJ, et al. This review will describe how these concerns emerged, the difficulties in determining causality followed by the evidence linking antipsychotics to the development of diabetes. Torniainen M, Mittendorfer-Rutz E, Tanskanen A, Bjorkenstam C, Suvisaari J, Alexanderson K, et al. Diabetologia. Epub 2007 Sep 4. The CHANGE trial: no superiority of lifestyle coaching plus care coordination plus treatment as usual compared to treatment as usual alone in reducing risk of cardiovascular disease in adults with schizophrenia spectrum disorders and abdominal obesity. Most studies report a higher rate of diabetes in patients who use antipsychotic medication than in non-users, and in patients taking atypical v. conventional antipsychotics. Ishoy PL, Knop FK, Broberg BV, Bak N, Andersen UB, Jorgensen NR, et al. All studies lasted less than 1year but when the studies were assessed according to duration, differences between antipsychotics were only found in studies lasting longer than 12weeks. This site needs JavaScript to work properly. Antipsychotics are increasingly prescribed for a wide range of mental health disorders among children and adolescents, a significant proportion of which are for adjunctive use for depression. Randomised controlled trials in the general population have demonstrated the effectiveness of lifestyle intervention to prevent diabetes [47,48,49,50,51]. Further testing should be performed 34months later to identify the small number of people who develop diabetes rapidly after starting antipsychotic treatment and annually thereafter. Ramachandraiah CT, Subramaniam N, Tancer M. The story of antipsychotics: past and present. Would you like email updates of new search results? As well as the adverse effect on glucose and body weight, antipsychotics also worsen the lipid profile and so it may be expected that the incidence of . Subjects with type 1 diabetes treated with antipsychotics (60% males, 40% females; mean duration of antipsychotic medication use 9.1 months) were significantly older (17.0 vs. 15.5 years of age; P < 0.001) and had a longer diabetes duration (7.2 vs. 5.1 years; P < 0.001) compared with subjects without antipsychotic medication. 2001;344(18):134350. Behav Brain Res. Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis. 2014;26(6):135568. In 2010, Rummel-Kluge et al. de Silva VA, Suraweera C, Ratnatunga SS, Dayabandara M, Wanniarachchi N, Hanwella R. Metformin in prevention and treatment of antipsychotic induced weight gain: a systematic review and meta-analysis. This article is part of the Topical Collection on Other Forms of Diabetes and Its Complications. -, Vancampfort D, Wampers M, Mitchell AJ, Correll CU, De Herdt A, Probst M, et al. Consensus development conference on antipsychotic drugs and obesity and diabetes. Effect of liraglutide treatment on prediabetes and overweight or obesity in clozapine- or olanzapine-treated patients with schizophrenia spectrumd: a randomized clinical trial. 2010;12:CD006629. 2023 Springer Nature Switzerland AG. N Engl J Med. Orlistat in clozapine- or olanzapine-treated patients with overweight or obesity: a 16-week randomized, double-blind, placebo-controlled trial. Mediating role of coping styles on the relationship between personality types and mental disorders in cardiovascular patients: a cross-sectional study in Iran. The relative risks for diabetes appear to be higher in adolescents and young adults. 2017;19(2):16271. Association between antipsychotic drugs and diabetes. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay V. The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). For example, in schizophrenic patients, the use of alternative medications such as aripiprazole can have a low risk of increasing weight (16, 17). Engl J, Laimer M, Niederwanger A, Kranebitter M, Starzinger M, Pedrini MT, et al. Antipsychotic drugs suppress the AKT/NF-kappaB pathway and regulate the differentiation of T-cell subsets. Naslund JA, Whiteman KL, McHugo GJ, Aschbrenner KA, Marsch LA, Bartels SJ. Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis. Elevated hemoglobin A1c as a possible indicator of diabetes mellitus and diabetic ketoacidosis in schizophrenia patients receiving atypical antipsychotics. Treatment is associated with a lower risk of hospitalisation, suicide and all-cause mortality [22, 46]. These drugs are highly obesogenic drugs and more than 7% weight gain occurs in 1572% of people taking second-generation antipsychotics [30]. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Treatment is associated with a lower risk of hospitalisation, suicide and all-cause mortality [22, 46]. have published a network meta-analysis of 47 studies with 114 comparisons [18]. Richard I.G. Holt, R.I.G. Please enable it to take advantage of the complete set of features! Whether antipsychotics alter resting energy expenditure through altered thermogenesis is uncertain with conflicting results in the literature [32, 36]. CAS Federal government websites often end in .gov or .mil. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. The second-generation antipsychotics have a lower affinity for the D2 receptors, with the exception of aripiprazole, which is a partial D2 agonist (Table (Table1).1). Although 9 individuals were subsequently confirmed to have type 1 diabetes, antipsychotics were implicated in the remainder. Article Mukundan A, Faulkner G, Cohn T, Remington G. Antipsychotic switching for people with schizophrenia who have neuroleptic-induced weight or metabolic problems. 2004;42(12):116775. PubMed Central The most convenient test is HbA1c but this may be falsely negative if there is a rapid onset of hyperglycaemia as sometimes happens after beginning antipsychotic treatment. The prevalence of diabetes is 2-3-fold higher in people with severe mental illness than the general population. Holt RIG, Gossage-Worrall R, Hind D, Bradburn MJ, McCrone P, Morris T, et al. Diabetes occurs at an earlier age and acute metabolic emergencies and diabetes complications have a greater impact in people with severe mental illness. Studies in people who are nave to antipsychotic treatment are particularly relevant because these individuals have no residual effect of previous exposure to antipsychotics. The mechanisms underlying the development of insulin resistance are not fully understood and may occur at many levels of insulin signalling. Siskind DJ, Russell AW, Gamble C, Winckel K, Mayfield K, Hollingworth S, et al. JAMA Psychiatry. J Clin Psychiatry. Atypical antipsychotics and glucose homeostasis. Antipsychotics associated with the development of type 2 diabetes in antipsychotic-naive schizophrenia patients. The report also found that the development of diabetes was associated with current use of olanzapine and clozapine while aripiprazole was associated with a lower risk. There is an emerging literature on the effect of antipsychotics on gestational diabetes. More in-depth overview of the mechanisms linking antipsychotics and the development of diabetes. government site. First-generation antipsychotics are dopamine receptor antagonists (DRA) and are known as typical antipsychotics. First-generation antipsychotics also antagonise dopamine receptors in the nigrostriatal and tuberinfundibular system causing extrapyramidal movement disorders and hyperprolactinaemia respectively. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. A second class of antipsychotics, the butyrophenones, was developed in the late 1950s [4]. The hazard ratio was greatest for clozapine (HR 2.58) but this was not statistically significant because the numbers taking clozapine were so small. Pillinger T, Beck K, Gobjila C, Donocik JG, Jauhar S, Howes OD. The history of clozapine and its emergence in the US market: a review and analysis. Diabetes mellitus and severe mental illness: mechanisms and clinical implications. 2016;15(2):16674. Daumit GL, Dickerson FB, Wang NY, Dalcin A, Jerome GJ, Anderson CA, et al. CAS However, this risk should be balanced with the potential cardiovascular benefits of this class of drugs. Further research is needed to understand how antipsychotics cause diabetes and to improve the clinical management of diabetes in people with severe mental illness. Richard I. G. Holt, Corresponding Author. and transmitted securely. Abstract Purpose of Review The prevalence of diabetes is 2-3-fold higher in people with severe mental illness than the general population. J Psychopharmacol. Further research is needed to understand how antipsychotics cause diabetes and to improve the clinical management of diabetes in people with severe mental illness. An official website of the United States government. Antipsychotic drugs suppress the AKT/NF-kappaB pathway and regulate the differentiation of T-cell subsets. Antipsychotics and the gut microbiome: olanzapine-induced metabolic dysfunction is attenuated by antibiotic administration in the rat. Antipsychotics appear to increase appetite by inhibiting these receptors. The most convenient test is HbA1c but this may be falsely negative if there is a rapid onset of hyperglycaemia as sometimes happens after beginning antipsychotic treatment. 2017;40(9):77181. A further literature review found 65 case reports of diabetic ketoacidosis, involving monotherapy with olanzapine (n=26), clozapine (n=17), risperidone (n=6), aripiprazole (n=6), quetiapine (n=3) and polypharmacy (n=7) [45]. 2013;42(3):54563. This review will examine the latest epidemiological studies linking antipsychotics and diabetes, as well as the mechanisms underlying the association and the clinical implications to minimise the impact of antipsychotics on metabolic health. PubMed Central Provided by the Springer Nature SharedIt content-sharing initiative, Over 10 million scientific documents at your fingertips, Not logged in NON-FDA APPROVED USES Dementia (behavioral disturbances) Substance abuse (reduction in use) Assessment and treatment of physical health problems among people with schizophrenia: national cross-sectional study. As well as the adverse effect on glucose and body weight, antipsychotics also worsen the lipid profile and so it may be expected that the incidence of macrovascular disease would differ between antipsychotics. Alghamdi F, Guo M, Abdulkhalek S, Crawford N, Amith SR, Szewczuk MR. A novel insulin receptor-signaling platform and its link to insulin resistance and type 2 diabetes. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). 2007;68(4):53341. published a systematic review of 48 studies comparing the head-to-head metabolic side effects of second-generation antipsychotics [17]. Blocking 2 adrenergic receptors increases basal insulin secretion. Google Scholar. Studies have demonstrated an association between antipsychotic medications and metabolic problems such as weight gain and diabetes mellitus in non-pregnant patients with psychiatric disorders. 2015;11(2):7989. While the risk of developing diabetes-related microvascular complications is higher in people taking antipsychotic medication, it is unknown whether this differs between antipsychotics . Ziprasidone, lurasidone and aripiprazole were associated with the least effect. 2021;46(11):18-30. 2005;48(9):19412. Nevertheless, the risk of diabetes needs to be considered and strategies developed to prevent diabetes, screen and diagnose diabetes and manage diabetes if it occurs. Ulcickas Yood M, Delorenze GN, Quesenberry CP, Jr, Oliveria SA, Tsai AL, Kim E, et al. The quality of metabolic side effect reporting in randomised clinical trials has improved over the last decade but caution is still needed because most trials are underpowered to examine changes in glucose and are often of too short a duration given the long natural history of diabetes. Antipsychotics exert their therapeutic effect, predominantly through antagonism of the dopamine D2 receptor; however, many also exert effects at serotonin, histamine and adrenergic receptors. eCollection 2023 Mar. Animal and cell culture experiments have shown the olanzapine and clozapine impair insulin secretion [1]. 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