Olanzapine is an atypical antipsychotic that is used currently in the treatment of schizophrenia and bipolar illness. Olanzapine is not infrequently associated with serum aminotransferase elevations during therapy and there have been rare instances of clinically apparent acute liver injury linked to its use.


Olanzapine (oh lan' za peen) is a thienobenzodiazepine derivative which appears to act as a dopamine (D1-4) and serotonic (5-HT2A/2C and 5-HT6) receptor antagonist. Olanzapine was approved for use in schizophrenia in the United States in 1996 and continues to be used for this indication. Olanzapine is also used in mood disturbances of bipolar I disorder and in combination with other agents for treatment of resistant depression in adults. Olanzapine is available as tablets of 2.5, 5, 7.5, 10, 15, and 20 mg generically and under the brand name Zyprexa; formulations for parenteral use and orally disintegrating tablets are also available, as are fixed combinations with antidepressants such as fluoxetine (Symbyax and generics). A typical dose regimen is 5 to 20 mg daily, starting with a low dose and increasing cautiously. Common side effects include sedation, increased appetite, weight gain, constipation, orthostatic hypotension, dizziness, dry mouth, weakness and akathisia (restlessness). Uncommon but potentially severe adverse reactions include excess mortality in the elderly with dementia, suicidal ideation and behaviors, neuroleptic malignant syndrome, hypersensitivity reactions including drug-rash, eosinophilia and systemic symptoms (DRESS) syndrome, metabolic abnormalities including hyperglycemia and dyslipidemia, seizures, leukopenia and neutropenia, and hyperprolactinemia. Like many antipsychotic medications, olanzapine has a boxed warning for increased risk of death in elderly patients with dementia-related psychosis.


Liver test abnormalities have been reported to occur in 10% to 50% of patients on long term therapy with olanzapine. These abnormalities are usually mild, asymptomatic and transient, and can reverse even with continuation of medication. In addition, instances of more marked elevations in serum aminotransferase levels and clinically apparent hepatitis with jaundice have been reported in patients taking olanzapine. Among atypical antipsychotic agents, olanzapine has most often been linked to cases of clinically apparent liver injury, the incidence being estimated to be 1:1200 treated patients. The time to onset of liver injury with olanzapine therapy in generally within 1 to 4 weeks of starting therapy or achieving optimal daily dose. However, cases with onset a year after starting have also been reported. The pattern of serum enzyme elevations is most often mixed (Case) but can range from hepatocellular to cholestatic. Fatal cases of olanzapine induced liver injury have been reported, but most cases resolve rapidly once olanzapine is stopped. Allergic manifestations (rash, fever, eosinophilia) and autoimmune markers are uncommon. Cases with a long latency and accompanied by significant weight gain may represent nonalcoholic fatty liver disease, rather than olanzapine hepatotoxicity.

Likelihood score: A (well known cause of clinically apparent liver injury).

Mechanism of Injury

The mechanism by which olanzapine causes serum aminotransferase elevations is not known. Some instances of ALT elevations occurring on olanzapine therapy may be due to nonalcoholic fatty liver disease caused by weight gain that occurs in at least one-quarter of treated patients generally during the first 1 to 2 years of therapy. Weight gain averages 1 kg/month and can be extreme (20 to 30 kg). Olanzapine has extensive hepatic metabolism, partially via the cytochrome P450 system, and some cases of clinically apparent hepatotoxicity may be due to production of a toxic intermediate of metabolism.

Outcome and Management

The serum aminotransferase elevations that occur on olanzapine therapy are usually self-limited and rarely require dose modification or discontinuation of therapy. No instances of chronic liver disease or vanishing bile duct syndrome have been attributed to olanzapine. Switching to other atypical antipsychotics is occasionally, but usually not associated with recurrence of hepatic injury.

Drug Class: Antipsychotic Agents, Atypicals


Case 1. Acute liver injury due to olanzapine.(1)

A 47 year old patient with a history of paranoid schizophrenia developed jaundice 11 months after starting olanzapine (10 mg daily). She had a vague history of alcoholic liver disease. Laboratory test results showed a total bilirubin of 7.5 mg/dL, ALT 173 U/L and alkaline phosphatase of 178 U/L (Table). Olanzapine was stopped and haloperidol started in its place. Tests for viral hepatitis and autoantibodies were negative. Within 2 weeks, serum bilirubin levels had fallen and all test results returned to normal when she was seen 3 months later.

Key Points

Laboratory Values


A brief case report with missing information but somewhat typical presentation of drug induced liver injury with a mixed hepatocellular-cholestatic pattern. Olanzapine is a common cause of transient serum aminotransferase elevations, but has rarely been implicated in cases of clinically apparent liver injury with jaundice.



Olanzapine – Generic, Zyprexa®


Antipsychotic Agents


Product labeling at DailyMed, National Library of Medicine, NIH



Domínguez-Jiménez JL, Puente-Gutiérrez JJ, Pelado-García EM, Cuesta-Cubillas D, García-Moreno AM. Liver toxicity due to olanzapine. Rev Esp Enferm Dig. 2012;104:617–8. [PubMed: 23368661]


References updated: 06 June 2023

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    (17 year old man developed jaundice 8 days after starting olanzapine for schizophrenia [bilirubin 7.2 mg/dL, ALT 120 U/L, Alk P 250 rising to 440 U/L], resolving within 2 months of stopping).
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    (35 year old man with chronic hepatitis C developed asymptomatic rise in ALT [188 to 721 U/L] and GGT [134 to 648 U/L] 2 months after starting clozapine, improving on stopping and recurring one month after starting olanzapine [ALT 166 to 714 U/L], resolving upon stopping again).
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    (Worldwide pharmacovigilance database contained 9036 hepatic adverse drug reactions in children, olanzapine ranked 16th with 62 reports [adjusted reporting odds ratio of 3.1], and clozapine ranked 38th with 36 cases [0.8]).
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    (45 year old woman with intermittent mild elevations of ALT during therapy with olanzapine and clozapine [ALT 16-92 U/L, AST 16-46 U/L, GGT 26-269 U/L, bilirubin not given]).
  • Domínguez-Jiménez JL, Puente-Gutiérrez JJ, Pelado-García EM, Cuesta-Cubillas D, García-Moreno AM. Liver toxicity due to olanzapine. Rev Esp Enferm Dig. 2012;104:617–8. [PubMed: 23368661]
    (47 year old developed jaundice 11 months after starting olanzapine [bilirubin 7.5 mg/dL, ALT 173 U/L, Alk P 178 U/L], resolving within 3 months of stopping: Case 1).
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    (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 5 cases [0.6%] were attributed to antipsychotic agents, including 3 due to quetiapine and 2 to olanzapine]).
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    (Extensive systematic review of the literature on the problem of weight gain during therapy with antipsychotic agents mentions that weight gain of 7% or more occurs in 18-40% of patients on olanzapine and averages +2.0 to + 4.3 kg, rates being higher than any other atypical antipsychotics, the majority of weight gain occurring during the first 6-12 months but not leveling off thereafter even with long term use).
  • Drugs for psychotic disorders. Med Lett Drugs Ther. 2016;58(1510):160–4. [PubMed: 27960194]
    (Concise review of medications available in the US for therapy of psychotic disorders; mentions that olanzapine can cause aminotransferase elevations, and that olanzapine and ziprasidone can cause DRESS syndrome, but does not mention ALT elevations or hepatotoxicity for any of agents discussed, including aripiprazole, brexpiprazole, cariprazine, clozapine, quetiapine, risperidone, asenapine, iloperidone, paliperidone and lurasidone).
  • Morlán-Coarasa MJ, Arias-Loste MT, Ortiz-García de la Foz V, Martínez-García O, Alonso-Martín C, Crespo J, Romero-Gómez M, et al. Incidence of non-alcoholic fatty liver disease and metabolic dysfunction in first episode schizophrenia and related psychotic disorders: a 3-year prospective randomized interventional study. Psychopharmacology (Berl). 2016;233:3947–52. [PubMed: 27620899]
    (Among 205 patients started on atypical antipsychotic agents between 2005 and 2012 followed using surrogate markers for fatty liver disease and for fibrosis [Fib-4], 48 [25%] patients developed evidence of fatty liver disease as assessed by a fatty liver index score, driven largely by weight gain [91%] and increases in waist circumference [69%] and triglycerides [54%]).
  • Dönmez YE, Özcan Ö, Soylu N, Sarıoğlu FK, Selimoğlu A. Management of hepatotoxicity Induced by the use of olanzapine. J Child Adolesc Psychopharmacol. 2017;27:293–4. [PubMed: 28398814]
    (15 year old male with new onset schizophrenia was started on olanzapine and developed abnormal ALT levels [84 U/L] within 2-8 weeks, which resolved with starting ursodiol and vitamin E allowing for continuation of olanzapine).
  • Baeza I, de la Serna E, Calvo-Escalona R, Merchán-Naranjo J, Rodríguez-Latorre P, Martínez-Cantarero MC, Andrés P, et al. One-year prospective study of liver function tests in children and adolescents on second-generation antipsychotics: is there a link with metabolic syndrome? J Child Adolesc Psychopharmacol. 2018;28:463–73. [PubMed: 29975563]
    (Among 216 children and adolescents starting atypical antipsychotics, mean weight gain at 6 months was 6.5 kg and mean ALT levels increased by 8.6 U/L, while among 37 taking olanzapine mean weight gain was 10.3 kg and ALT increase 2.6 U/L; increases in ALT associated most closely with development of the metabolic syndrome, mean ALT increasing by 27.8 U/L at 6 months).
  • Gómez-Lumbreras A, Marcos-Fosch C, Aguilera C. Psychotropic drugs and liver toxicity. Am J Ther. 2018;25:e601–e602. [PubMed: 30188878]
    (Woman developed jaundice 4 months after starting paroxetine [40 mg daily] and olanzapine [2.5 mg daily] [bilirubin 7.3 mg/dL, ALT 984 U/L, Alk P 174 U/L], resolving within 3 weeks of stopping both).
  • Dusi N, Comacchio C, Lasalvia A. Late-onset cholestatic liver injury during combination treatment with chlorpromazine and olanzapine: a case report. J Clin Psychopharmacol. 2019;39:175–6. [PubMed: 30640795]
    (40 year old man develop jaundice 10 days after increasing the dose of olanzapine [from 10 to 15 mg daily] which he had taken for 8 years and while also receiving chlorpromazine for 15 months [bilirubin 26.6 rising to 33.3 mg/dL, ALT 51 U/L, Alk P 285 U/L], biopsy showing cholestatic hepatitis and jaundice persisting for 3 months).
  • Patel H, Shirk D, Lowery J. Letter to the Editor: Role of vitamin E in olanzapine-induced hepatotoxicity. J Child Adolesc Psychopharmacol. 2020;30:576. [PubMed: 32746620]
    (15 year old with disruptive mood disorder developed ALT elevations [17 rising to 110 U/L] on olanzapine, which was treated with vitamin E [100 mg daily] with prompt fall of ALT [43 U/L] and subsequent rise again when vitamin E was stopped [62 U/L], and improvement again with restarting [24 U/L]).
  • Druschky K, Toto S, Bleich S, Baumgärtner J, Engel RR, Grohmann R, Maier HB, et al. Severe drug-induced liver injury in patients under treatment with antipsychotic drugs: data from the AMSP study. World J Biol Psychiatry. 2021;22:373–386. [PubMed: 32892689]
    (Among 246 cases of severe liver injury due to antipsychotic medications identified in a prospective registry of German psychiatric hospitals between 1993 and 2016, 46 arose in 38,349 patients [0.12%] who received clozapine [34 as a single antipsychotic agent]; other commonly implicated agents being olanzapine [n=90 of 54,822: 0.16%], quetiapine [34 of 66,209: 0.05%] and risperidone [27 of 51,683: 0.05%]; two fatal cases occurred in olanzapine treated patients).
  • Zeiss R, Hafner S, Schönfeldt-Lecuona C, Connemann BJ, Gahr M. Drug-associated liver injury related to antipsychotics: exploratory analysis of pharmacovigilance data. J Clin Psychopharmacol. 2022;42:440–444. [PubMed: 35730552]
    (Review of the VigiBase data base of individual case safety reports on antipsychotics and liver injury found positive hepatic safety signals for olanzapine and clozapine, but none for risperidone, quetiapine, ziprasidone, asenapine, aripiprazole, brexpiprazole, and cariprazine).
  • Brelje A, Fay B, Mariouw S, VandenBerg A. Identifying olanzapine induced liver injury in the setting of acute hepatitis C: A case report. Ment Health Clin. 2022;12:210–213. [PMC free article: PMC9190265] [PubMed: 35801165]
    (27 year old woman with drug use and acute psychosis was found to have ALT elevations [482 U/L] and HCV RNA in serum on hospitalization, ALT levels worsening [to 1456 U/L] after starting olanzapine which improved when it was stopped, follow up on HCV status not provided).
  • Echater S, Hasnaoui M, El Bouchali W, Elghazouani F. Cas clinique du mois. Hépatite cholestatique aiguë associée à l’olanzapine chez une patiente bipolaire. Rev Med Liege. 2022;77:80–84. [Acute cholestatic hepatitis associated with olanzapine in a patient with bipolar disorder] French. [PubMed: 35143126]
    (43 year old woman with bipolar disorder type 1 with an acute manic episode despite valproate developed jaundice, vomiting and pruritus 2 weeks after starting olanzapine and 3 days after dose increase to 20 mg/day [bilirubin 14.6 mg/dL, ALT 370 U/L, Alk P 782 U/L], with improvement on stopping and resolution within 1 month).
  • Gunther M, Dopheide JA. Antipsychotic safety in liver disease: a narrative review and practical guide for the clinician. J Acad Consult Liaison Psychiatry. 2023;64:73–82. [PubMed: 36180017]
    (Review of the literature on hepatotoxicity of antipsychotic medications and guidance on their use in patients with liver disease characterizes chlorpromazine, clozapine, and olanzapine as having the greatest risk for causing liver injury, quetiapine and risperidone as having moderate risk, haloperidol as having low risk and paliperidone, aripiprazole, lurasidone, and loxapine as having low risk).