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Table of Contents
LETTER TO THE EDITOR
Year : 2020  |  Volume : 34  |  Issue : 3  |  Page : 143-145

Pancreatitis as a rare side effect of paliperidone use


Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Date of Submission05-Jun-2020
Date of Decision23-Jul-2020
Date of Acceptance03-Aug-2020
Date of Web Publication28-Sep-2020

Correspondence Address:
Tsung- Hua Lu
No. 138, Sheng Li Road, North District, Tainan 704
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/TPSY.TPSY_24_20

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How to cite this article:
Wu CL, Lu TH. Pancreatitis as a rare side effect of paliperidone use. Taiwan J Psychiatry 2020;34:143-5

How to cite this URL:
Wu CL, Lu TH. Pancreatitis as a rare side effect of paliperidone use. Taiwan J Psychiatry [serial online] 2020 [cited 2020 Oct 28];34:143-5. Available from: http://www.e-tjp.org/text.asp?2020/34/3/143/296460



Although gallstones and alcohol are the most common causes of acute pancreatitis, many causes of acute pancreatitis remain unknown. No reports exist on pancreatitis associated with paliperidone use although several case reports of acute pancreatitis exist during the use of antipsychotic medications. In this letter-to-the editor, we present a case of acute pancreatitis following the use of paliperidone.


  The Case Report Top


The patient is a 55-year-old male patient who has a history of schizophrenia and had many medical conditions (brain atrioventricular malformation status postleft frontotemporal craniotomy) since 1997 (aged 33 years), type 2 diabetes mellitus, coronary artery disease, status poststenting for the left anterior descending coronary artery in October 2016, and peripheral arterial occlusive disease of both lower extremities with occlusion of the left anterior tibial artery in July 2016.

Besides having carbamazepine (1997–2002), he received antipsychotic treatments with trifluoperazine (1997–2002), clotiapine (2002–2015, and 2017), risperidone (2013–2015), haloperidol (2015–2016), aripiprazole (July 2016–July 2017), and paliperidone (July 2017–January 2020).

The patient presented himself with intermittent fever with dull pain without radiation to back for two weeks in the right upper quadrant (RUQ) and the right lower quadrant (RLQ) of the abdomen, for two weeks in July 2018. On the day of the admission, he complained about decreased appetite and diarrhea but denied any tarry stool or bloody stool. Gastrointestinal examination showed tenderness on the RUQ and RLQ with normal bowel sounds.

Patient's initial blood counts showed elevated white blood cell (WBC) count with normal differential counts (WBC = 12,200 cells/μL). He also had elevated serum levels of lipase (1,184 U/L) and C-reactive protein (34.6 mg/L) without transaminitis hyperbilirubinemia or elevated levels of calcium, lactate dehydrogenase, or IgG4 (72.5 mg/dL). Computed tomography of the abdomen with contrast revealed focal pancreatitis at head portion, as well as loculated or turbid fluids at mesenteric root and proximal transverse pericolic region. Magnetic resonance cholangiopancreatography showed focal pancreatitis at head portion of the pancreas, with secondary change of pseudocysts, loculated or turbid fluids at mesenteric root and proximal transverse pericolic region, but no image finding of cannabidiol stone or biliary/pancreatic duct dilatation.

The patient denied history of alcohol use. Acute pancreatitis was diagnosed, and this was the first time he was admitted for pancreatitis. He received nothing by month with adequate hydration was given for two days, and then, he tried diet smoothly. He received empirical antibiotic with cefuroxime due to his possible diverticulitis. His condition was improved and he was discharged 1 week later (lipase was 784 U/L at discharge). Then, he kept outpatient clinic follow-up. No definite cause of pancreatitis was confirmed.

The patient had another admission for pancreatitis in October 2019, when he presented himself with RUQ abdominal pain for 1 day with fever and diarrhea. Gastrointestinal examination showed epigastric and RUQ tenderness with muscle guarding and hypoactive bowel sounds. Blood counts showed elevated white blood cell count with neutrophil predominant (WBC = 14.1k cells/μL, segments = 79.4%). He had elevated serum levels of lipase (153 U/L) without transaminitis hyperbilirubinemia and elevated serum levels of calcium or triglyceride. The computed tomography of the abdomen with contrast revealed the finding of a pseudocyst with lobulated fluid collection at pancreatic head, and an abscess formation in the right upper quadrant, attaching to hepatic flexure of the colon with local colon wall thickening and fat stranding. He was admitted after acute or chronic pancreatitis with abscess formation was diagnosed.

Drug-related pancreatitis was suspected because no new etiology was identified. Tracing back to his medication use history, the patient kept taking carvedilol since November 2016, clopidogrel since November 2016, glimepiride since March 2017, metformin since March 2017, sitagliptin since May 2017, and paliperidone since July 2017. Paliperidone was discontinued for suspected drug-related pancreatitis. Nothing by mouth with parenteral adequate hydration was given for two days, and then, he received total parenteral nutrition due to limited improvement of abdominal pain. Empirical antibiotic with cefotaxime was given and later switched to ceftazidime and metronidazole for conservative treatment for intra-abdominal infection. His condition was improved gradually, and he was discharged three weeks later. His antipsychotic agent was changed to aripiprazole in January 2020. Until April 2020, the patient had no longer had any episode of pancreatitis.


  Comment Top


In our case, the patient had many underlying diseases, which make it difficult to identify the possible cause of pancreatitis. There was no evidence of gallstones, alcohol, hypertriglyceridemia, biliary obstruction, hypercalcemia, or autoimmune disease in this patient. There was no previous study indicating any direct evidence that coronary artery disease-related pancreatitis is secondary to ischemia of pancreatic vessels. Therefore, we suspected drug-induced pancreatitis. In a systemic review of case reports, the investigators mentioned glimepiride-, sitagliptin-, and metformin-related pancreatitis[1]. One meta-analysis reported small absolute increased risk for pancreatitis with DPP-4i therapy, but the finding is not increased in sitagliptin, saxagliptin, and alogliptin group separately when compared with placebo[2]. Furthermore, no stronger evidence exists for hypoglycemic agent-induced pancreatitis.

Previously, there were inconclusive results of the association between pancreatitis and paliperidone. In the population-based nested case–control study[3], Boden et al. mentioned the second-generation (atypical) antipsychotic-induced metabolic syndrome with elevated serum triglyceride levels is a possible risk factor of pancreatitis and that the lack of association between antipsychotic drugs and acute pancreatitis after adjustment for confounding factors[3]. The investigators suggested that the previously reported positive associations might be explained by confounding factors[3]. A retrospective study investigating the related numbers of pancreatitis in 192 patients treated with the three second-generation antipsychotic agents versus the conventional neuroleptic haloperidol showed the results that the rate is 40% with clozapine, 33% with olanzapine, and 16% with risperidone, and 12% with haloperidol, suggesting a greater risk with the second-generation antipsychotic agents[4]. Among those, no studies examined paliperidone alone. No significant association has been implicated between paliperidone and acute pancreatitis.

Paliperidone is an active metabolite of risperidone. Although no confirmed relationship exists between paliperidone and pancreatitis, there are some case reports of risperidone-induced pancreatitis[5]. In a case report of risperidone-induced pancreatitis, a 7-year, 10-month-old-boy was treated with risperidone in one drug trial, and the pancreatitis was subsided after risperidone was discontinued[5]. Another case report showed risperidone-induced hyperamylasemia, hyperlipasemia, and neuroleptic malignant syndrome in a patient with schizophrenia, and in this case, amylasemia and lipasemia are progressively reduced, returning within normal range in 20 days after stopping risperidone, which the patient had been taking for the previous two years[6].

Pancreatitis due to glimepiride, metformin, or sitagliptin use could not be totally ruled out; we tried to clarify the most possible medication related to pancreatitis chronologically. Tracing back to the medication history in our case, the most recent use of medication was paliperidone, and the patient received aripiprazole rather than paliperidone for preventing further pancreatitis. He had not had any new episode of acute pancreatitis at least for six months.

We also used Naranjo scale[7] to evaluate the likelihood of adverse drug reactions from paliperidone, and total scale reveals 2 (possible adverse drug reaction) [Table 1]. While there is still much to learn about the pathogenesis of atypical antipsychotic-induced pancreatitis, especially paliperidone, we suggest that further study is needed to investigate the actual relationship between paliperidone and risk of pancreatitis. (The institutional review board at National Cheng Kung University Hospital gave IRB-exempted status for this case report for publication [the IRB protocol number = A-EC-109-017, date of approval = June 22, 2020) without any need of obtaining the informed consent from the patient).
Table 1: The score of Naranjo scale[7] for this patient

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  Financial Support and Sponsorship Top


None.


  Conflicts of Interest Top


The authors declare no conflicts of interest.



 
  References Top

1.
Wolfe D, Kanji S, Yazdi F, et al.: Drug induced pancreatitis: a systematic review of case reports to determine potential drug associations. PLoS One 2020; 15: e0231883.  Back to cited text no. 1
    
2.
Buse JB, Bethel MA, Green JB, et al.: Pancreatic safety of sitagliptin in the TECOS study. Diabetes Care 2017; 40: 164-70.  Back to cited text no. 2
    
3.
Boden R, Bexelius TS, Mattsson F, et al.: Antidopaminergic drugs and acute pancreatitis: a population-based study. BMJ Open 2012; 2: e000914.  Back to cited text no. 3
    
4.
Koller EA, Cross JT, Doraiswamy PM, et al.: Pancreatitis associated with atypical antipsychotics: from the Food and Drug Administration's MedWatch surveillance system and published reports. Pharmacotherapy 2003; 23: 1123-30.  Back to cited text no. 4
    
5.
Hanft A, Bourgeois J: Risperidone and pancreatitis. J Am Acad Child Adolesc Psychiatry 2004; 43: 1458-9.  Back to cited text no. 5
    
6.
Ghio L, Fornaro G, Rossi P: Risperidone-induced hyperamylasemia, hyperlipasemia, and neuroleptic malignant syndrome: a case report. J Clin Psychopharmacol 2009; 29: 391-2.  Back to cited text no. 6
    
7.
Naranjo CA, Busto U, Sellers EM, et al.: A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239-45.  Back to cited text no. 7
    



 
 
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