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Open Journal of Psychiatry, 2012, 2, 110-112 OJPsych http://dx.doi.org/10.4236/ojpsych.2012.22015 Published Online April 2012 (http://www.SciRP.org/journal/ojpsych/)

Case report: Olanzapine-induced acute and new mellitus

Erik Monasterio1*, Ruchi Bhalla2, Andrew McKean3

1Department of Psychological Medicine, University of Otago, Christchurch, New Zealand 2Hammersmith and Fulham Mental Health Unit, West London Mental Health NHS Trust, London, UK 3Hillmorton Hospital, Christchurch, New Zealand Email: *[email protected]

Received 29 December 2011; revised 31 January 2012; accepted 15 February 2012

ABSTRACT criteria and required application from a psychiatrist for a patient who had been trialled unsuccessfully on risperi- The aim of this case study is to review the literature done or required treatment with olanzapine short acting and report the first published case of olanzapine-in- intra-muscular injection [4]. In June 2011, significantly duced acute pancreatitis in New Zealand. A case re- cheaper generic versions of olanzapine were introduced port of acute pancreatitis with new onset diabetes and the special authority criteria for olanzapine with- mellitus secondary to olanzapine in a 42-year-old male, drawn [5]. We aim to highlight lesser known and poten- in the absence of medical risk factors is reported. tially fatal side effects through our case report. Eleven previous case reports of olanzapine induced acute-pancreatitis were identified in the literature. A 2. CASE REPORT 42-year-old male was diagnosed with acute pancreati- tis and new diabetes mellitus induced by olanzapine. Mr. X is a 42 year old man who had come into contact Although rare, pancreatitis is associated with use of with mental health services on many occasions during some atypical medications. It is impor- the last two decades, due to recurrent depressive episodes. tant for prescribers to be aware of this potentially The clinical opinion over the years wavered towards low fatal side effect. In addition to this, we are highlight- grade depressive and anxiety difficulties with Cluster B ing the well documented evidence of metabolic dis- personality traits. From assessment notes dating back to ruption associated with olanzapine. 1994, it was noted that he had been prescribed 100 mg nocte for treatment of his depressive symptoms Keywords: Case Report; Olanzapine; Pancreatitis; with its additional benefit of sedation. In 2006 he was Diabetes Mellitus commenced on olanzapine for its mood stabilising prop- erties after he failed to respond to mood stabilising medications. At the time there was no clinical indication 1. INTRODUCTION that he suffered from a psychotic illness. Adverse side-effects associated with the use atypical In February 2010, four years after commencing olan- antipsychotic medications (AAPs) are widely recognised; zapine 10 mg daily, Mr. X became acutely medically un- this has led to specific recommendations for regular side stable; he was transferred to a surgical ward following a effect monitoring throughout a course of treatment [1,2]. twenty-four hour history of sudden onset, non-radiating Adverse outcomes include over sedation, metabolic de- abdominal pain, associated with nausea. He denied a rangement, extrapyramidal side effects, myocarditis, pro- history of gallstones or trauma. He had a minimal medi- longed QTc interval, toxic megacolon and agranulocyto- cal history of mild asthma. There was no past or present sis [1-3]. history of use or abuse. Although there was a The aim of this case report is to review the literature family history of bipolar affective disorder affecting Mr. X’s brother, there was no known family history of pan- and describe the first published episode of olanzapine- creatitis or type II diabetes mellitus. induced pancreatitis in New Zealand. On examination, Mr. X was tachycardic and tachyp- Olanzapine was first funded in New Zealand in 1999/ noeic. Abdominal examination revealed mild distension 2000 by the Pharmaceutical Management Agency with tenderness in the epigastrium and right upper quad- (PHARMAC). Its use was restricted by special authority rant. Air entry was decreased bibasally on chest ausculta- *Corresponding author. tion. Blood tests indicated acute inflammation with a

OPEN ACCESS E. Monasterio et al. / Open Journal of Psychiatry 2 (2012) 110-112 111 leukocytosis (white blood cell count 11.8; normal range revealed 11 case reports from 2000 to the current date 4 - 11 × 109/L) neutrophilia (neutrophil count 9.1; nor- [6-13] but no case reports in Australasia. There are no mal range 2.5 - 7.5 × 109/L) and raised C reactive pro- reports on doxepin-related pancreatitis from 1966 to the tein of 43 (normal range < 10). Amylase was elevated at current date. Given the lack evidence in the literature for 358 (normal range < 180 U/L) with high lipase of 358 doxepin causing pancreatitis, and taking into considera- (normal range 7 - 60 U/L). Urea and electrolytes (in- tion that Mr. X had been taking doxepin for 12 years be- cluding calcium) liver function tests, including GGT and fore developing pancreatitis and has continued to take fasting were all normal. Glycosylated hae- this after recovering from this condition, doxepin is moglobin was raised at 11.1% (normal range 6.5% - unlikely to have played a role. In order to more clearly 7.4%). Chest radiograph showed patchy pulmonary opac- determine the likelihood that olanzapine caused the epi- ity at the left lung base and atelectasis at the right lung sode of pancreatitis in this case rather than an underlying base. Ultrasound imaging of the abdomen displayed an disease or other factors, we have applied the Naranjo increase in liver echogenicity with no focal lesions and algorithm [14] (a logical evaluation procedure for deter- no evidence of gallstones. The pancreas, spleen and kid- mining the likelihood of an adverse drug reaction); we neys appeared normal. obtained a score of 5, which rates the likelihood as The absence of any alcohol intake, trauma or gall- “probable”. The mechanism by which olanzapine causes stones, in addition to normal lipids, electrolytes and ul- pancreatitis is unclear. A well recognised consequence of trasound imaging prompted a diagnosis of acute pan- olanzapine use is hyperlipidaemia, which in itself is creatitis secondary to olanzapine. The patient was man- known to precipitate acute pancreatitis [1-3]. In 2007 aged with supportive treatment of intravenous fluids, Rossor et al. [8] described a case of chylomicronemia oxygen and analgesia. A secondary finding of new type thought to be caused by olanzapine prescribed in a 36- II diabetes mellitus was established, and Mr. X was year-old gentleman diagnosed with schizoaffective dis- commenced on insulin and . He made a good order. Six weeks after the introduction of olanzapine, he recovery, olanzapine was discontinued and outpatient was diagnosed with acute pancreatitis with no other ob- diabetes follow-up was arranged. vious risk factors. Interestingly, the patient described in When seen in Diabetes clinic four months later, gly- our report had normal serum levels. A 2000 cosylated haemoglobin had fallen from 11.1% to 6.3%. correspondence article [10] and a subsequent case report At the time, Mr. X had been complaining of frequent [6] outline three cases of pancreatitis associated with sig- dizziness, tiredness and hunger between insulin injec- nificant alcohol intake, well beyond the national recom- tions and especially overnight. The impression was that mended guidelines. The authors proposed that olanzapine of hypoglycaemic events with rebound hyperglycaemia should be used in caution with patients who drink alco- in the morning and evening. His insulin doses were re- hol on a regular basis or who have a history of previous duced with Metformin maintained. On review by the pancreatitis. Although in Mr. X and other reports [9,13] same Diabetes specialist after another four months, gly- pancreatitis occurred more than one year after treatment, cosylated haemoglobin had fallen further to 6.0% and the in most reported cases [8,9,15] pancreatitis occurred within insulin was stopped. Given the marked improvement in six months of starting the medication. The Food and Drug glucose control since olanzapine was stopped Mr. X was Administration’s Medwatch pharmacoviligance study of discharged from further Diabetic Outpatient follow-up. pooled, spontaneously reported adverse events revealed He has been under the care of his general practitioner that of 192 patients who developed pancreatitis with one and has maintained normal glucose levels with Met- or more antipsychotic agents 40%, 33%, 16% and 12% formin, 500 mg BD. were in patients receiving treatment with , In December 2010, ten months after discharge from olanzapine, and , respectively; in hospital, Mr. X was admitted for inpatient psychiatric 50% of patients treated with haloperidol they were also care. He presented with symptoms of schizophreniform receiving an AAP medication; was co-pre- characterised by delusional beliefs of a perse- scribed in 23% of patients; and 22 patients died [15]. In cutory nature with associated perceptual disturbances, of addition there have been a total of 26 reports of pan- two months duration. He responded favourably to treat- creatitis associated with olanzapine use to the UK MHRA ment with the antipsychotic agent amisulpiride 400 mg spontaneous reporting scheme, with one fatality reported BD without evidence of metabolic impairment. He has [16]. been discharged from hospital and at 4 month follow-up Our study highlights diabetes mellitus as another im- his mental state and diabetic control have remained stable. portant complication of olanzapine therapy. Olanzapine 3. DISCUSSION induced diabetes mellitus is well documented in the lit- erature [1-3,17]. A 2002 retrospective epidemiological A PubMed search of olanzapine induced pancreatitis study by Koller et al. [17] uncovered one hundred and

Copyright © 2012 SciRes. OPEN ACCESS 112 E. Monasterio et al. / Open Journal of Psychiatry 2 (2012) 110-112 eighty eight cases of new-onset diabetes mellitus fol- notification. www.pharmac.govt.nz lowing the introduction of olanzapine. When it was dis- [6] Collin, A., Clevenot, D., Moulin, P., Macabeo, C. and continued or the dosage decreased, seventy-eight percent David, J.S. (2009) Acute pancreatitis induced by olanzap- of patients had improved glycaemic control. Hypergly- ine. Annales Françaises d’Anesthésie et de Réanimation caemia recurred in eight of ten cases with olanzapine 28, 907-909. doi:10.1016/j.annfar.2009.09.002 rechallenge. This demonstrated a similar pattern of re- [7] Kahn, D. and Bourgeois, J.A. (2007) Acute pancreatitis sults in our patient, whose blood levels markedly and in a schizophrenic patient tak- ing olanzapine. Journal of Clinical Psychopharmacology, improved with the discontinuation of olanzapine. The 27, 397-400. doi:10.1097/01.jcp.0000264990.93652.80 exact cause of glucose dysregulation with olanzapine is [8] Rossor, A.M., Leech, N. and Neely, R.D. (2007) Olan- unclear. It is hypothesised [18] that antagonism of 5- zapine induced chylomicronemia presenting as acute pan- HT1A () receptors may decrease the respon- creatitis. Journal of Clinical Psychopharmacology, 27, siveness of pancreatic beta-cells, thus reducing insulin 395-396. doi:10.1097/01.jcp.0000264988.55603.bb secretion precipitating hyperglycaemia. A recent study [9] Waage, C., Carlsson, H. and Nilsen, E.W. (2004) Olan- by Chiu et al. [19] looked at the time-dependent effects zapine induced pancreatitis: A case report. Journal of the of olanzapine treatment in naïve Pancreas, 5, 388-391. schizophrenic patients. The metabolic parameters were [10] Hagger, R., Brown, C. and Hurley, P. (2000) Olanzapine quantitatively assessed at zero, two, four and eight weeks and pancreatitis. British Journal of Psychiatry, 177, 567. by the intravenous glucose tolerance test. Insulin secre- doi:10.1192/bjp.177.6.567 tion significantly increased at week two, returned to [11] Doucette, D.E., Grenier, J.P. and Robertson, P.S. (2000) baseline at week four and significantly increased again at Olanzapine-induced acute pancreatitis. The Annals of Phar- week eight. The researchers concluded that olanzapine macotherapy, 34, 1128-1131. doi:10.1345/aph.19390 may directly influence pancreatic beta cell function to [12] Belli, H., Sertbas, Y. and Bayik, Y. (2005) Olanzapine- cause deficiency in insulin secretion, thus precipitating induced diabetes due to pancreatitis. Indian Journal of hyperglycaemia. Gastroenterology, 24, 273. [13] Bracamonte, J., Underhill, M. and Sarmiento, P. (2010) 4. CONCLUSION Acute pancreatitis associated with lisinopril and olanzap- ine. American Journal of Health-System Pharmacy, 67, The aim of our report is to highlight a case of acute pan- 214-216. doi:10.2146/ajhp080519 creatitis with new onset diabetes mellitus secondary to [14] Naranjo, C.A., Busto, U., Sellers, E.M., et al. (1981) A olanzapine, at a time when it is being removed from the method for estimating the probability of adverse drug re- New Zealand PHARMAC Special Authority funding list. actions. Clinical Pharmacology & Therapeurics, 30, 239- We strongly anticipate a rise in its prescription in the 245. doi:10.1038/clpt.1981.154 community. The case of Mr. X highlights just how im- [15] Koller, E., Cross, J., Doraiswamy, P. and Malozowski, S. portant this metabolic screening is, particularly in view (2003) Pancreatitis associated with atypical antipsychot- of potentially fatal side effects such as acute pancreatits ics: From the food and drug administration’s medwatch surveillance system and published reports. Pharmaco- and ketoacidosis. It is hoped that this report will alert therapy, 23, 1123-1130. clinicians to such consequences, with the aim to improve doi:10.1592/phco.23.10.1123.32759 screening and reduce acute medical complications. [16] Anon (2011) United Kingdom MHRA olanzapine drug

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