Metabolic disorders induced by psychotropic drugs.

J60AR2IKIC (Clozapine); N7U69T4SZR (Olanzapine); Psychotropic Drugs; Humans; Clozapine; Olanzapine; Psychotropic Drugs/adverse effects; Metabolic Diseases/chemically induced/epidemiology; Metabolic Syndrome/chemically induced/epidemiology; Antidepressant; Antidépresseur; Antipsychotic; Antipsychotique; Diabetes; Diabète; Dyslipidemia; Dyslipidémie; Prise de poids; Schizophrenia; Schizophrénie; Weight gain

Abstract :

[en] Psychotropic drugs may be associated with metabolic disorders, often but not only triggered by weight gain. Disorders include dysglycemia and diabetes, atherogenic dyslipidemia and metabolic syndrome. Overall, metabolic risk is lower with antidepressants than with antipsychotics. Among antidepressants, metabolic disorders may occur with both selective serotonin reuptake inhibitors and tricyclics, but with some between-molecule differences in each pharmacological family. Among antipsychotics, the risk is higher with second-generation (atypical) than first-generation agents. Higher risk was reported with clozapine and olanzapine, and lower risk with risperidone and aripiprazole. Weight gain is associated with increased insulin resistance, but impaired insulin secretion was also reported with clozapine and olanzapine. Metabolic disorders may be attenuated by the medication withdrawal and replacement by another safer drug. Besides deleterious effects of medications, the psychiatric population is also exposed to bad lifestyle habits (unhealthy diet and sedentary life), which also increase the risk of metabolic disorders. Management should first reinforce lifestyle measures. If this proves insufficient, specific drugs may be considered to tackle the metabolic disorder on a strategy similar to that applied in the general population.

Disciplines :

Endocrinology, metabolism & nutrition
Pharmacy, pharmacology & toxicology
Psychiatry

Author, co-author :

Scheen, André ; Centre Hospitalier Universitaire de Liège - CHU > > Service de diabétologie, nutrition, maladies métaboliques ; Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine,

Language :

English

Title :

Metabolic disorders induced by psychotropic drugs.

Publication date :

May 2023

Journal title :

Annales d'Endocrinologie

ISSN :

0003-4266

Volume :

Issue :

Pages :

357-363

Peer reviewed :

Editorial reviewed

Commentary :

Available on ORBi :

since 01 June 2023

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Bibliography

Fathallah, N., Slim, R., Larif, S., Hmouda, H., Ben Salem, C., Drug-induced hyperglycaemia and diabetes. Drug Saf 38 (2015), 1153–1168.
Feve, B., Scheen, A.J., When therapeutic drugs lead to diabetes. Diabetologia 65 (2022), 751–762.
Leslie, W.S., Hankey, C.R., Lean, M.E., Weight gain as an adverse effect of some commonly prescribed drugs: a systematic review. QJM 100 (2007), 395–404.
Wofford, M.R., King, D.S., Harrell, T.K., Drug-induced metabolic syndrome. J Clin Hypertens (Greenwich) 8 (2006), 114–119.
Wharton, S., Raiber, L., Serodio, K.J., Lee, J., Christensen, R.A., Medications that cause weight gain and alternatives in Canada: a narrative review. Diabetes Metab Syndr Obes 11 (2018), 427–438.
Penninx, B., Lange, S.M.M., Metabolic syndrome in psychiatric patients: overview, mechanisms, and implications. Dialogues Clin Neurosci 20 (2018), 63–73.
Vancampfort, D., Stubbs, B., Mitchell, A.J., De Hert, M., Wampers, M., Ward, P.B., et al. Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis. World Psychiatry 14 (2015), 339–347.
Freyberg, Z., Aslanoglou, D., Shah, R., Ballon, J.S., Intrinsic and antipsychotic drug-induced metabolic dysfunction in schizophrenia. Front Neurosci, 11, 2017, 432.
McIntyre, R.S., Park, K.Y., Law, C.W., Sultan, F., Adams, A., Lourenco, M.T., et al. The association between conventional antidepressants and the metabolic syndrome: a review of the evidence and clinical implications. CNS Drugs 24 (2010), 741–753.
Woo, Y.S., Lim, H.K., Wang, S.M., Bahk, W.M., Clinical evidence of antidepressant effects of insulin and anti-hyperglycemic agents and implications for the pathophysiology of depression – a literature review. Int J Mol Sci, 21, 2020, 6969.
Livingstone, C., Rampes, H., Lithium:, a review of its metabolic adverse effects. J Psychopharmacol 20 (2006), 347–355.
Gomes-da-Costa, S., Marx, W., Corponi, F., Anmella, G., Murru, A., Pons-Cabrera, M.T., et al. Lithium therapy and weight change in people with bipolar disorder: a systematic review and meta-analysis. Neurosci Biobehav Rev, 134, 2022, 104266.
Prillo, J., Soh, J.F., Park, H., Beaulieu, S., Linnaranta, O., Rej, S., Obesity and metabolic comorbidity in bipolar disorder: do patients on lithium comprise a subgroup? A naturalistic study. BMC Psychiatry, 21, 2021, 558.
Jindal, R.D., Keshavan, M.S., Critical role of M3 muscarinic receptor in insulin secretion: implications for psychopharmacology. J Clin Psychopharmacol 26 (2006), 449–450.
Cipriani, A., Furukawa, T.A., Salanti, G., Geddes, J.R., Higgins, J.P., Churchill, R., et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet 373 (2009), 746–758.
McIntyre, R.S., Soczynska, J.K., Konarski, J.Z., Kennedy, S.H., The effect of antidepressants on glucose homeostasis and insulin sensitivity: synthesis and mechanisms. Expert Opin Drug Saf 5 (2006), 157–168.
Andersohn, F., Schade, R., Suissa, S., Garbe, E., Long-term use of antidepressants for depressive disorders and the risk of diabetes mellitus. Am J Psychiatry 166 (2009), 591–598.
Khoza, S., Barner, J.C., Bohman, T.M., Rascati, K., Lawson, K., Wilson, J.P., Use of antidepressant agents and the risk of type 2 diabetes. Eur J Clin Pharmacol 68 (2012), 1295–1302.
Miidera, H., Enomoto, M., Kitamura, S., Tachimori, H., Mishima, K., Association between the use of antidepressants and the risk of type 2 diabetes: a large, population-based cohort study in Japan. Diabetes Care 43 (2020), 885–893.
Azevedo Da Silva, M., Fournier, A., Boutron-Ruault, M.C., Balkau, B., Bonnet, F., Nabi, H., et al. Increased risk of type 2 diabetes in antidepressant users: evidence from a 6-year longitudinal study in the E3N cohort. Diabet Med 37 (2020), 1866–1873.
Barnard, K., Peveler, R.C., Holt, R.I., Antidepressant medication as a risk factor for type 2 diabetes and impaired glucose regulation: systematic review. Diabetes Care 36 (2013), 3337–3345.
Weston-Green, K., Huang, X.F., Deng, C., Second generation antipsychotic-induced type 2 diabetes: a role for the muscarinic M3 receptor. CNS Drugs 27 (2013), 1069–1080.
Tran, Y.H., Schuiling-Veninga, C.C.M., Bergman, J.E.H., Groen, H., Wilffert, B., Impact of muscarinic M(3) receptor antagonism on the risk of type 2 diabetes in antidepressant-treated patients: a case-controlled study. CNS Drugs 31 (2017), 483–493.
Burcu, M., Zito, J.M., Safer, D.J., Magder, L.S., dosReis, S., Shaya, F.T., et al. Association of antidepressant medications with incident type 2 diabetes among medicaid-insured youths. JAMA Pediatr., 171, 2017, 1200–1207.
Sun, J.W., Hernandez-Diaz, S., Haneuse, S., Bourgeois, F.T., Vine, S.M., Olfson, M., et al. Association of selective serotonin reuptake inhibitors with the risk of type 2 diabetes in children and adolescents. JAMA Psychiatry 78 (2021), 91–100.
Roopan, S., Larsen, E.R., Use of antidepressants in patients with depression and comorbid diabetes mellitus: a systematic review. Acta Neuropsychiatr 29 (2017), 127–139.
Srisurapanont, M., Suttajit, S., Kosachunhanun, N., Likhitsathian, S., Suradom, C., Maneeton, B., Antidepressants for depressed patients with type 2 diabetes mellitus: a systematic review and network meta-analysis of short-term randomized controlled trials. Neurosci Biobehav Rev, 139, 2022, 104731.
Wu, C.S., Hsu, L.Y., Pan, Y.J., Wang, S.H., Associations between antidepressant use and advanced diabetes outcomes in patients with depression and diabetes mellitus. J Clin Endocrinol Metab 106 (2021), e5136–e5146.
Ko, Y.C., Lee, C.H., Wu, C.S., Huang, Y.J., Comparison of efficacy and safety of gabapentin and duloxetine in painful diabetic peripheral neuropathy: a systematic review and meta-analysis of randomised controlled trials. Int J Clin Pract, 75, 2021, e14576.
Alonso-Pedrero, L., Bes-Rastrollo, M., Marti, A., Effects of antidepressant and antipsychotic use on weight gain: a systematic review. Obes Rev 20 (2019), 1680–1690.
Serretti, A., Mandelli, L., Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry 71 (2010), 1259–1272.
Gill, H., Gill, B., El-Halabi, S., Chen-Li, D., Lipsitz, O., Rosenblat, J.D., et al. Antidepressant medications and weight change: a narrative review. Obesity 28 (2020), 2064–2072.
Gramaglia, C., Gambaro, E., Bartolomei, G., Camera, P., Chiarelli-Serra, M., Lorenzini, L., et al. Increased risk of metabolic syndrome in antidepressants users: a mini review. Front Psychiatry, 9, 2018, 621.
McIntyre, R.S., Soczynska, J.K., Konarski, J.Z., Kennedy, S.H., The effect of antidepressants on lipid homeostasis: a cardiac safety concern?. Expert Opin Drug Saf 5 (2006), 523–537.
Himmerich, H., Minkwitz, J., Kirkby, K.C., Weight gain and metabolic changes during treatment with antipsychotics and antidepressants. Endocr Metab Immune Disord Drug Targets 15 (2015), 252–260.
Luo, H., Jiang, Z.L., Ren, Y., Therapy management of metabolic disorder comorbidity with depression. Front Psychol, 12, 2021, 683320.
Moulton, C.D., Hopkins, C.W.P., Ismail, K., Stahl, D., Repositioning of diabetes treatments for depressive symptoms: a systematic review and meta-analysis of clinical trials. Psychoneuroendocrinology 94 (2018), 91–103.
Kessing, L.V., Rytgaard, H.C., Ekstrom, C.T., Knop, F.K., Berk, M., Gerds, T.A., Antidiabetes agents and incident depression: a nationwide population-based study. Diabetes Care 43 (2020), 3050–3060.
Wium-Andersen, I.K., Osler, M., Jorgensen, M.B., Rungby, J., Wium-Andersen, M.K., Diabetes, antidiabetic medications and risk of depression – a population-based cohort and nested case-control study. Psychoneuroendocrinology, 140, 2022, 105715.
Detka, J., Glombik, K., Insights into a possible role of glucagon-like peptide-1 receptor agonists in the treatment of depression. Pharmacol Rep 73 (2021), 1020–1032.
Gamble, J.M., Chibrikov, E., Midodzi, W.K., Twells, L.K., Majumdar, S.R., Examining the risk of depression or self-harm associated with incretin-based therapies used to manage hyperglycaemia in patients with type 2 diabetes: a cohort study using the UK Clinical Practice Research Datalink. BMJ open, 8, 2018, e023830.
Holt, R.I.G., Association between antipsychotic medication use and diabetes. Curr Diabetes Rep, 19, 2019, 96.
Scheen, A.J., De Hert, M.A., Abnormal glucose metabolism in patients treated with antipsychotics. Diabetes Metab 33 (2007), 169–175.
Vancampfort, D., Correll, C.U., Galling, B., Probst, M., De Hert, M., Ward, P.B., et al. Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: a systematic review and large scale meta-analysis. World Psychiatry 15 (2016), 166–174.
Hirsch, L., Yang, J., Bresee, L., Jette, N., Patten, S., Pringsheim, T., Second-generation antipsychotics and metabolic side effects: a systematic review of population-based studies. Drug Saf 40 (2017), 771–781.
Pillinger, T., McCutcheon, R.A., Vano, L., Mizuno, Y., Arumuham, A., Hindley, G., et al. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. Lancet Psychiatry 7 (2020), 64–77.
Grajales, D., Ferreira, V., Valverde, A.M., Second-generation antipsychotics and dysregulation of glucose metabolism: beyond weight gain. Cells, 8, 2019, 1336.
Polcwiartek, C., Vang, T., Bruhn, C.H., Hashemi, N., Rosenzweig, M., Nielsen, J., Diabetic ketoacidosis in patients exposed to antipsychotics: a systematic literature review and analysis of Danish adverse drug event reports. Psychopharmacology (Berl) 233 (2016), 3663–3672.
American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinology, North American Association for the Study of Obesity, Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 27 (2004), 596–601.
Chen, J., Huang, X.F., Shao, R., Chen, C., Deng, C., Molecular mechanisms of antipsychotic drug-induced diabetes. Front Neurosci, 11, 2017, 643.
Cernea, S., Dima, L., Correll, C.U., Manu, P., Pharmacological management of glucose dysregulation in patients treated with second-generation antipsychotics. Drugs 80 (2020), 1763–1781.
Singh, R., Bansal, Y., Medhi, B., Kuhad, A., Antipsychotics-induced metabolic alterations: recounting the mechanistic insights, therapeutic targets and pharmacological alternatives. Eur J Pharmacol 844 (2019), 231–240.
Siskind, D., Hahn, M., Correll, C.U., Fink-Jensen, A., Russell, A.W., Bak, N., et al. Glucagon-like peptide-1 receptor agonists for antipsychotic-associated cardio-metabolic risk factors: a systematic review and individual participant data meta-analysis. Diabetes Obes Metab 21 (2019), 293–302.
Barton, B.B., Segger, F., Fischer, K., Obermeier, M., Musil, R., Update on weight-gain caused by antipsychotics: a systematic review and meta-analysis. Expert Opin Drug Saf, 2020;19:295-314.
Stogios, N., Smith, E., Bowden, S., Tran, V., Asgariroozbehani, R., McIntyre, W.B., et al. Metabolic adverse effects of off-label use of second-generation antipsychotics in the adult population: a systematic review and meta-analysis. Neuropsychopharmacology 47 (2022), 664–672.
He, M., Deng, C., Huang, X.F., The role of hypothalamic H1 receptor antagonism in antipsychotic-induced weight gain. CNS Drugs 27 (2013), 423–434.
Raben, A.T., Marshe, V.S., Chintoh, A., Gorbovskaya, I., Muller, D.J., Hahn, M.K., The complex relationship between antipsychotic-induced weight gain and therapeutic benefits: a systematic review and implications for treatment. Front Neurosci, 11, 2017, 741.
Agarwal, S.M., Stogios, N., Ahsan, Z.A., Lockwood, J.T., Duncan, M.J., Takeuchi, H., et al. Pharmacological interventions for prevention of weight gain in people with schizophrenia. Cochrane Database Syst Rev, 10, 2022, CD013337.
Mazereel, V., Detraux, J., Vancampfort, D., van Winkel, R., De Hert, M., Impact of psychotropic medication effects on obesity and the metabolic syndrome in people with serious mental illness. Front Endocrinol (Lausanne) 11 (2020), 5734–5779.
De Hert, M., Schreurs, V., Sweers, K., Van Eyck, D., Hanssens, L., Sinko, S., et al. Typical and atypical antipsychotics differentially affect long-term incidence rates of the metabolic syndrome in first-episode patients with schizophrenia: a retrospective chart review. Schizophr Res 101 (2008), 295–303.
Meyer, J.M., Koro, C.E., The effects of antipsychotic therapy on serum lipids: a comprehensive review. Schizophr Res 70 (2004), 1–17.
Bernardo, M., Rico-Villademoros, F., Garcia-Rizo, C., Rojo, R., Gomez-Huelgas, R., Real-world data on the adverse metabolic effects of second-generation antipsychotics and their potential determinants in adult patients: a systematic review of population-based studies. Adv Ther 38 (2021), 2491–2512.
Vazquez-Bourgon, J., Ortiz-Garcia de la Foz, V., Gomez-Revuelta, M., Mayoral-van Son, J., Juncal-Ruiz, M., Garrido-Torres, N., et al. Aripiprazole and risperidone present comparable long-term metabolic profiles: data from a pragmatic randomized controlled trial in drug-naive first-episode psychosis. Int J Neuropsychopharmacol 25 (2022), 795–806.
Kouidrat, Y., Amad, A., De Hert, M., Emerging drugs and indications for cardio-metabolic disorders in people with severe mental illness. Curr Pharm Des 21 (2015), 3317–3324.