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Risperidone and Hepatotoxicity in Children and Adolescent: A Literature Review

Year 2020, Volume: 2 Issue: 1, 54 - 58, 04.04.2020
https://doi.org/10.35365/ctjpp.20.2.8

Abstract

Risperidone is a second generation anti-psychotic drug that is commonly preferred in the treatment of schizophrenia, attention deficit hyperactivity disorder and bipolar disorders. Risperidone-associated hepatic adverse effects have long been investigated and continues to be unclear. In this review, our aim is to establish the possible hepatic adverse effects linked to risperidone treatment in children and adolescent in terms of severities and reversibility. We performed literature search via electronic databases (PubMed, Embase and the Cochrane Library) in August 2019. Risperidone treatment may lead to alterations in liver function test (LFT), mostly asymptomatic and reversible with the discontinuation or normalizes with time. Furthermore, there are few cases reporting risperidone-induced cholestatic hepatitis and immunoallergic hepatitis. Although exact mechanism of action of risperidone on liver remains unknown, there are growing evidences that link alterations of fatty acid biosynthesis to hepatic adverse effects. We recommend physicians to take basal LFT prior to risperidone treatment and monitor LFT during treatment. Additionally, physicians should be aware that most alterations at LFT associated with risperidone use are asymptomatic and reversible. However, more comprehensive studies investigating risperidone-associated hepatic adverse effects should be performed to reach a definitive outcome.

References

  • Atasoy, N., Erdogan, A., Yalug, I., Öztürk, Ü., Konuk, N., Atik, L. (2007). A review of liver function tests during treatment with atypical antipsychotic drugs: A chart review study. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 31(6), 1255- 60.
  • Auger, F., Patrick, D., Françoise, M., Nizard, M.F., Durieux, N., Bordet, R. (2014). Long-term risperidone treatment induces visceral adiposity associated with hepatic steatosis in mice: A magnetic resonance approach. Schizophrenia Research and Treatment, 11.
  • Azirak, S., Bilgic, S., Tastemir, K., Güvenç, A.N., Kocaman, N., Özer, M.K. (2019). The protective effect of resveratrol against risperidone-induced liver damage through an action on fas gene expression. General Physiology and Biophysics, 38(3), 215-225.
  • Baeza, I., Serna, E., Calvo-Escalona, R., Naranjo, M.J., Latorre, R.P., Martinenz-Cantarero, C.M. (2018). One-year prospective study of liver function tests in children and adolescents on second-generation antipsychotics: Is there a link with metabolic syndrome? Journal of Child and Adolescent Psychopharmacology, 28(7), 463-73.
  • Cohen, L.J. (1994). Risperidone. The Journal of Human Pharmacology and Drug Therapy,14(3), 253-265.
  • Copur, M., Erdogan, A. (2011). Risperidone rechallenge for marked liver function test abnormalities in an autistic child. Recent Patents on Endocrine, Metabolic & Immune Drug Discovery, 5(3), 237-239.
  • Cordeiro, Q., Elkis, H. (2007). Pancreatitis and cholestatic hepatitis induced by risperidone. Journal of Clinical Psychopharmacology, 21(5), 529-30.
  • Eftekhari, A., Ahmad-Durieuxsian, E., Azarmi, Y., Parvizpur, A., Hamishehkar, H., Eghbal, M.A. (2016). In vitro/vivo studies towards mechanisms of risperidone-induced oxidative stress and the protective role of coenzyme q10 and n-acetylcysteine. Toxicology Mechanisms and Methods, 26(7), 520-528.
  • Erdogan, A., Atasoy, N., Akkurt, H., Öztürk, D., Karaahmet, E., Yaluğ, İ. (2008). Risperidone and liver function tests in children and adolescents: A short-term prospective study. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 32(3), 849-57.
  • Erdogan, A., Karaman, M., Ozdemir, E., Yurteri, N., Tufan, E.A., Turcer, A.M. (2010). Six months of treatment with risperidone may be associated with nonsignificant abnormalities of liver function tests in children and adolescents: A longitudinal, observational study from turkey. Journal of Child and Adolescent Psychopharmacology, 20(5), 407-13.
  • Esposito, D., Brocvielle, H., Becquemont, L., Hardy, P., Chouinard, G., Corruble, E. (2005). Risperidone-induced immune allergic hepatitis. American Journal of Psychiatry, 162(10), 1984.
  • Findling, R.L., McNamara, N.K., Branicky, L.A., Schluchter, M.D., Lemon, E., Blumer J.L. (2000). A double-blind pilot study of risperidone in the treatment of conduct disorder. Journal of American Academy of Child and Adolescent Psychiatry, 39(4), 509-516
  • Francisca, L., Carmen, H., Nuria, B., Ros, B.N. (2005). Acute cholestatic hepatitis probably associated with risperidone. The International Journal of Psychiatry in Medicine, 35(2), 199-205.
  • Halıcı, Z., Keleş, O., Kaplan, S. (2008). Chronically Administered Risperidone Did Not Change the Number of Hepatocytes in Rats: A Stereological and Histopathological Study. Basic & Clinical Pharmacology & Toxicology, 102(5), 426-32.
  • Holtmann, M., Kopf, D., Mayer, M., Behtinger, E., Schmidt, H.M. (2004). Risperidone-associated steatohepatitis and excessive weight-gain. Pharmacopsychiatry, 36(5), 206-7.
  • Horska, K., Ruda-Kucerova, J., Karpisek, M., Suchy, M., Opatrilova, R., Kotolova, H. (2017). Depot risperidone-induced adverse metabolic alterations in female rats. Journal of Psychopharmacology, 31(4), 487-499.
  • Hosseini, S., Ahmadi, A. (2012). Peripheral edema occurring during treatment with risperidone combined with citalopram. Case Reports in Medicine, 540732
  • Karaman, M., Erdogan, A., Tufan, E., Yurteri, N., Özdemir, E., Ankaralı, H. (2011). Liver function tests in children and adolescents receiving risperidone treatment for a year: A longitudinal, observational study from Turkey. International Journal of Psychiatry in Clinical Practice, 15(3), 204-8.
  • Krebs, S., Dormann, H., Muth-Selbach, U., Selkchard, H., Kay, B., Thomas, H.C. Risperidone-induced cholestatic hepatitis. European Journal of Gastroenterology and Hepatology, 2001; 13(1): 67-9.
  • Kumra, S., Herion, D., Jacobsen, L., Briguglia, C. (1997). Risperidone-induced hepatotoxicity in pediatric patients. Journal of the American Academy of Child and Adolescent Psychiatry, 36(5), 701-5.
  • López-Torres, E., Süveges, A., Peñas-Ledó, E., Dona, A., Dorado, P., Lerenna, L.A. (2014). Liver enzyme abnormalities during antipsychotic treatment: A case report of risperidone-associated hepatotoxicity. Drug Metabolism and Drug Interactions, 29(2), 123-6.
  • McCracken, J.T., McGough, J., Shah, B., Cronin, P., Hong, D., Aman, M.G. (2002). Risperidone in children with autism and serious behavioral problems. New England Journal of Medicine, 347, 314-21.
  • McNamara, R., Jandacek, R., Rider, T., Tso, P., Cole-Strauss, A., Lipton, W.J. (2011). Atypical antipsychotic medications increase postprandial triglyceride and glucose levels in male rats: Relationship with stearoyl-coa desaturase activity. Schizophrenia Research, 129(1), 66-73.
  • McNamara, R., Magrisso, I., Hofacer, R., Jandacek, R. (2012). Omega-3 fatty acid deficiency augments risperidone-induced hepatic steatosis in rats: Positive association with stearoyl-coa desaturase. Pharmacology Research, 66(4), 283-91.
  • Mouradian-Stamatiadis, L., Dumortier, G., Januel, D., Delmas, A.B., Cabaret, W. (2002). Liver function tests during treatment with antipsychotic drugs: A case series of 23 patients. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 26(7), 1409-11.
  • Scahill, L., Jeon, S., Boorin, S., McDougle, J.C., Aman, G.M., Dziura, J. (2016). Weight gain and metabolic consequences of risperidone in young children with autism spectrum disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 55(5), 415-23.
  • Snyder, R., Turgay, A., Aman, M., Binder, C., Fisman, S., Carroll A. (2002). Effects of risperidone on conduct and disruptive behavior disorders in children with subaverage IQs. Journal of the American Academy of Child and Adolescent Psychiatry, 41(9), 1026-36.
  • Szigethy, E., Wiznitzer, M., Branicky, L.A., Maxwell, K., Findling, R.L. (1999). Risperidone-induced hepatotoxicity in children and adolescents? A chart review study. Journal of Child and Adolescent Psychopharmacology, 9(2), 93-8.
  • Telles-Correia, D., Barbosa, A., Cortez-Pinto, H. (2017). Psychotropic Drugs and Liver Disease: A Critical Review of Pharmacokinetics and Liver Toxicity. World Journal of Gastrointestinal Pharmacology and Therapeutics, 8(1), 26–38.
  • Turgay, A., Binder, C., Snyder, R., Fisman, S. (2002). Long-term safety and efficacy of risperidone for the treatment of disruptive behavior disorders in children with subaverage IQs. Pediatrics, 110(3), 34.
  • Uchida, H., Pollock, B.G., Bies, R.R. (2009). Predicting age-Specific dosing of antipsychotics. Clinical Pharmacological Therapy, 86(4), 360-362.
  • Whitworth, A., Liensberger, D., Fleischhacker, W. (1999). Transient increase of liver enzymes induced by risperidone: Two case reports. Journal of Clinical Psychopharmacology, 19(5), 475-6.
  • Wright, T., Vandenberg, A. (2007). Risperidone- and quetiapine-induced cholestasis. Annals of Pharmacotherapy, 41(9), 1518-23.
Year 2020, Volume: 2 Issue: 1, 54 - 58, 04.04.2020
https://doi.org/10.35365/ctjpp.20.2.8

Abstract

References

  • Atasoy, N., Erdogan, A., Yalug, I., Öztürk, Ü., Konuk, N., Atik, L. (2007). A review of liver function tests during treatment with atypical antipsychotic drugs: A chart review study. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 31(6), 1255- 60.
  • Auger, F., Patrick, D., Françoise, M., Nizard, M.F., Durieux, N., Bordet, R. (2014). Long-term risperidone treatment induces visceral adiposity associated with hepatic steatosis in mice: A magnetic resonance approach. Schizophrenia Research and Treatment, 11.
  • Azirak, S., Bilgic, S., Tastemir, K., Güvenç, A.N., Kocaman, N., Özer, M.K. (2019). The protective effect of resveratrol against risperidone-induced liver damage through an action on fas gene expression. General Physiology and Biophysics, 38(3), 215-225.
  • Baeza, I., Serna, E., Calvo-Escalona, R., Naranjo, M.J., Latorre, R.P., Martinenz-Cantarero, C.M. (2018). One-year prospective study of liver function tests in children and adolescents on second-generation antipsychotics: Is there a link with metabolic syndrome? Journal of Child and Adolescent Psychopharmacology, 28(7), 463-73.
  • Cohen, L.J. (1994). Risperidone. The Journal of Human Pharmacology and Drug Therapy,14(3), 253-265.
  • Copur, M., Erdogan, A. (2011). Risperidone rechallenge for marked liver function test abnormalities in an autistic child. Recent Patents on Endocrine, Metabolic & Immune Drug Discovery, 5(3), 237-239.
  • Cordeiro, Q., Elkis, H. (2007). Pancreatitis and cholestatic hepatitis induced by risperidone. Journal of Clinical Psychopharmacology, 21(5), 529-30.
  • Eftekhari, A., Ahmad-Durieuxsian, E., Azarmi, Y., Parvizpur, A., Hamishehkar, H., Eghbal, M.A. (2016). In vitro/vivo studies towards mechanisms of risperidone-induced oxidative stress and the protective role of coenzyme q10 and n-acetylcysteine. Toxicology Mechanisms and Methods, 26(7), 520-528.
  • Erdogan, A., Atasoy, N., Akkurt, H., Öztürk, D., Karaahmet, E., Yaluğ, İ. (2008). Risperidone and liver function tests in children and adolescents: A short-term prospective study. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 32(3), 849-57.
  • Erdogan, A., Karaman, M., Ozdemir, E., Yurteri, N., Tufan, E.A., Turcer, A.M. (2010). Six months of treatment with risperidone may be associated with nonsignificant abnormalities of liver function tests in children and adolescents: A longitudinal, observational study from turkey. Journal of Child and Adolescent Psychopharmacology, 20(5), 407-13.
  • Esposito, D., Brocvielle, H., Becquemont, L., Hardy, P., Chouinard, G., Corruble, E. (2005). Risperidone-induced immune allergic hepatitis. American Journal of Psychiatry, 162(10), 1984.
  • Findling, R.L., McNamara, N.K., Branicky, L.A., Schluchter, M.D., Lemon, E., Blumer J.L. (2000). A double-blind pilot study of risperidone in the treatment of conduct disorder. Journal of American Academy of Child and Adolescent Psychiatry, 39(4), 509-516
  • Francisca, L., Carmen, H., Nuria, B., Ros, B.N. (2005). Acute cholestatic hepatitis probably associated with risperidone. The International Journal of Psychiatry in Medicine, 35(2), 199-205.
  • Halıcı, Z., Keleş, O., Kaplan, S. (2008). Chronically Administered Risperidone Did Not Change the Number of Hepatocytes in Rats: A Stereological and Histopathological Study. Basic & Clinical Pharmacology & Toxicology, 102(5), 426-32.
  • Holtmann, M., Kopf, D., Mayer, M., Behtinger, E., Schmidt, H.M. (2004). Risperidone-associated steatohepatitis and excessive weight-gain. Pharmacopsychiatry, 36(5), 206-7.
  • Horska, K., Ruda-Kucerova, J., Karpisek, M., Suchy, M., Opatrilova, R., Kotolova, H. (2017). Depot risperidone-induced adverse metabolic alterations in female rats. Journal of Psychopharmacology, 31(4), 487-499.
  • Hosseini, S., Ahmadi, A. (2012). Peripheral edema occurring during treatment with risperidone combined with citalopram. Case Reports in Medicine, 540732
  • Karaman, M., Erdogan, A., Tufan, E., Yurteri, N., Özdemir, E., Ankaralı, H. (2011). Liver function tests in children and adolescents receiving risperidone treatment for a year: A longitudinal, observational study from Turkey. International Journal of Psychiatry in Clinical Practice, 15(3), 204-8.
  • Krebs, S., Dormann, H., Muth-Selbach, U., Selkchard, H., Kay, B., Thomas, H.C. Risperidone-induced cholestatic hepatitis. European Journal of Gastroenterology and Hepatology, 2001; 13(1): 67-9.
  • Kumra, S., Herion, D., Jacobsen, L., Briguglia, C. (1997). Risperidone-induced hepatotoxicity in pediatric patients. Journal of the American Academy of Child and Adolescent Psychiatry, 36(5), 701-5.
  • López-Torres, E., Süveges, A., Peñas-Ledó, E., Dona, A., Dorado, P., Lerenna, L.A. (2014). Liver enzyme abnormalities during antipsychotic treatment: A case report of risperidone-associated hepatotoxicity. Drug Metabolism and Drug Interactions, 29(2), 123-6.
  • McCracken, J.T., McGough, J., Shah, B., Cronin, P., Hong, D., Aman, M.G. (2002). Risperidone in children with autism and serious behavioral problems. New England Journal of Medicine, 347, 314-21.
  • McNamara, R., Jandacek, R., Rider, T., Tso, P., Cole-Strauss, A., Lipton, W.J. (2011). Atypical antipsychotic medications increase postprandial triglyceride and glucose levels in male rats: Relationship with stearoyl-coa desaturase activity. Schizophrenia Research, 129(1), 66-73.
  • McNamara, R., Magrisso, I., Hofacer, R., Jandacek, R. (2012). Omega-3 fatty acid deficiency augments risperidone-induced hepatic steatosis in rats: Positive association with stearoyl-coa desaturase. Pharmacology Research, 66(4), 283-91.
  • Mouradian-Stamatiadis, L., Dumortier, G., Januel, D., Delmas, A.B., Cabaret, W. (2002). Liver function tests during treatment with antipsychotic drugs: A case series of 23 patients. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 26(7), 1409-11.
  • Scahill, L., Jeon, S., Boorin, S., McDougle, J.C., Aman, G.M., Dziura, J. (2016). Weight gain and metabolic consequences of risperidone in young children with autism spectrum disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 55(5), 415-23.
  • Snyder, R., Turgay, A., Aman, M., Binder, C., Fisman, S., Carroll A. (2002). Effects of risperidone on conduct and disruptive behavior disorders in children with subaverage IQs. Journal of the American Academy of Child and Adolescent Psychiatry, 41(9), 1026-36.
  • Szigethy, E., Wiznitzer, M., Branicky, L.A., Maxwell, K., Findling, R.L. (1999). Risperidone-induced hepatotoxicity in children and adolescents? A chart review study. Journal of Child and Adolescent Psychopharmacology, 9(2), 93-8.
  • Telles-Correia, D., Barbosa, A., Cortez-Pinto, H. (2017). Psychotropic Drugs and Liver Disease: A Critical Review of Pharmacokinetics and Liver Toxicity. World Journal of Gastrointestinal Pharmacology and Therapeutics, 8(1), 26–38.
  • Turgay, A., Binder, C., Snyder, R., Fisman, S. (2002). Long-term safety and efficacy of risperidone for the treatment of disruptive behavior disorders in children with subaverage IQs. Pediatrics, 110(3), 34.
  • Uchida, H., Pollock, B.G., Bies, R.R. (2009). Predicting age-Specific dosing of antipsychotics. Clinical Pharmacological Therapy, 86(4), 360-362.
  • Whitworth, A., Liensberger, D., Fleischhacker, W. (1999). Transient increase of liver enzymes induced by risperidone: Two case reports. Journal of Clinical Psychopharmacology, 19(5), 475-6.
  • Wright, T., Vandenberg, A. (2007). Risperidone- and quetiapine-induced cholestasis. Annals of Pharmacotherapy, 41(9), 1518-23.
There are 33 citations in total.

Details

Primary Language English
Subjects Psychiatry
Journal Section Review
Authors

Mazlum Çöpür This is me

Sidar Çöpür This is me

Publication Date April 4, 2020
Acceptance Date January 10, 2020
Published in Issue Year 2020 Volume: 2 Issue: 1

Cite

APA Çöpür, M., & Çöpür, S. (2020). Risperidone and Hepatotoxicity in Children and Adolescent: A Literature Review. Kıbrıs Türk Psikiyatri Ve Psikoloji Dergisi, 2(1), 54-58. https://doi.org/10.35365/ctjpp.20.2.8