Sertraline and acute pancreatitis: a case-report

Abstracts

A pancreatite aguda é uma patologia grave e com considerável morbidade e mortalidade. Vários fatores são apontados como possíveis causas de pancreatite aguda. Neste relato, será apresentado um caso de pancreatite aguda com possível associação causal com um inibidor seletivo de recaptura de serotonina: sertralina. Após um mês de tratamento com sertralina, uma paciente do sexo feminino, 55 anos, desenvolveu forte dor abdominal e elevação da amilase sérica. Após internação e retirada da sertralina, seus sintomas remitiram e os níveis de amilase voltaram ao normal. Pela potencial gravidade do quadro e pelo amplo uso desta medicação, tal associação deve ser lembrada em investigações de casos de pancreatite aguda.

Relato de caso; Pancreatite aguda; Sertralina; Inibidor seletivo de recaptura de serotonina

CASE REPORT

Sertraline and acute pancreatitis: a case-report

André Malbergier^I; Hercílio Pereira de Oliveira Júnior^II

^IInstitute of Psychiatry of the Clinical Hospital of the Medical School of the University of São Paulo. São Paulo, SP, Brazil

^IIDepartment of Psychiatry of the Clinical Hospital of the Medical School of the University of São Paulo. São Paulo, SP, Brazil

^{Correspondence}

ABSTRACT

Acute pancreatitis is a severe disease with considerable morbidity and mortality. Many risk factors are causally related to acute pancreatitis. In this report, a case of acute pancreatitis with possible causal relationship with the use of a selective serotonin reuptake inhibitor, sertraline, will be discussed. After one month of treatment with sertraline, a female patient, 55 years-old, developed a severe abdominal pain and showed a serum amylase elevation. She was admitted to the hospital and the use of sertraline was interrupted. After that, the symptoms remitted and the serum amylase level returned to normal. Because of the potential severity of this disease and the widespread use of sertraline, this association should be reminded when investigating possible causes for acute pancreatitis.

Keywords: Case report. Acute pancreatitis. Sertraline. Selective serotonin reuptake inhibitors.

Introduction

Acute pancreatitis is a severe disease with considerable morbidity and mortality. The incidence of acute pancreatitis is rising in Western countries.¹ Gallstones and alcohol consumption are the most important risk factors. Other risk factors include hyperlipidemia, hypercalcemia and trauma. In 10-25% of the patients with acute pancreatitis, no obvious risk factors are present.² Drugs are also associated with the event and pathogenesis of drug-induced acute pancreatitis has not been yet completely clarified.

Case-Report

A previously healthy 55-year-old woman was admitted to treatment for depression. She had quit smoking for five months and developed depressive symptoms (anhedonia, sexual impairment, depressive humor and weight loss). For several years before admission she has been taking methyldopa and thiazide diuretics for hypertension. She had no evidence of biliary tract and endocrine diseases or alcohol abuse.

She was treated with paroxetine, mirtazapine and diazepam without significant improvement of her depressive symptoms. These drugs were interrupted and the patient started to take sertraline 50 mg/day. One month later, the depressive symptoms started to improve and she was kept on sertraline, methyldopa and thiazide diuretic for three months. Suddenly she developed severe abdominal pain and was admitted to an emergency room. Laboratory results included: hemoglobin 13.1 g/dl (normal 10-12 g/dl), leucocytes 9.2X10³ u/mm³ (normal 5-10X10³ u/mm³), sodium 150 mmol/l (normal 140-148 mmol/l), potassium 3.5 mmol/l (normal 3.4-5.3 mmol/l), calcium 7.8 mmol/l (normal 8.5-10 mmol/l), aspartate transaminase 54 U/l (normal 15-37 U/l), alanine transferase 100 U/l (normal 30-65 U/l), alkaline phosphatase 131 U/l (normal 50-136 U/l) and serum amylase 708 U/l (normal 29-115 U/l). Abdominal ultrasound revealed a swollen pancreas.

Methyldopa is a widely used antihypertensive but has a high incidence of adverse effects.³ Acute pancreatitis has been described in association with methyldopa since 1978.^4-6 The majority of the patients experience a positive rechallenge reaction.

Acute pancreatitits secondary to the thiazides group of diuretics has been reported by many authors.^7,8 However, sometimes, this group of drugs is not included among the drugs which may produce acute pancreatitis.⁹

The patient described in this report had taken methyldopa and thiazide diuretics in association for many years without any side-effects, before the introduction of sertraline. Although the two antihypertensive drugs has been related to acute pancreatitis, sertraline was the first drug that was discontinued and two days later the serum amylase dropped to 62 U/l (normal 29-115 U/l) and she recovered completely. She was under observation for four months without taking any antidepressants and the depressive symptoms did not recur.

Discussion

Most evidence of association between drugs and acute pancreatitis is based on case reports.¹⁰

The World Health Organization (WHO) received a total of 2749 reports of drug-associated acute pancreatitis between 1968 and 1993. The most frequently reported drugs were: angiotensin-converting enzyme inhibitors (n=209), valproate (n=219), H2 receptor blockers (n=127), sulindac (n=121), azathioprine (n=73), genfibrozil (n=72), lovastatin (n=72), pentamidine (n=62) and didanosine (61)¹¹.

In the specific literature, drug-induced acute pancreatitis is labeled as definite when confirmed by computed tomography, laparotomy or autopsy. The diagnosis is also considered definite when positive findings on ultrasound are combined with abdominal pain and an elevated level of serum amylase or lipase. Probable diagnosis is labeled when two of the following three criteria are present: 1) positive findings on ultrasound examination, 2) abdominal pain and 3) elevated serum amylase or lipase. This patient had abdominal pain, increased serum amylase and positive findings on ultrasound, and therefore, a definite diagnosis.

Causality assessment between drug intake and development of acute pancreatitis is based on the temporal relationship, effect of dechallenge, rechallenge and the presence of other established causes (gallstones or alcohol abuse).¹⁰

The patient is still taking methyldopa and diuretics and she has no symptoms of pancreatitis. The patient had no other established causes like gallstones or alcohol abuse.

There are few reports of acute pancreatitis associated with psychiatric drugs. The most frequently described drugs are clozapine¹² and valproate. Valproate can cause a necro-hemorragic severe form associated with high mortality.¹³ The association between SSRI and acute pancreatitis is recognized by WHO, but so far there has been only one published case reporting acute pancreatitis in a Norwegian patient who was taking sertraline.¹⁴

In this case, besides the drugs, there were no other known risk factors for acute pancreatitis. The prompt recovery after the interruption of sertraline seems to be a strong evidence that her pancreatitis was induced by this drug.

References

1. Corfield AP, Cooper MJ, Williamsom RC et al. Prediction of severity in acute pancreatitis: Prospective comparison of three prognostic indices. Lancet 1985;2:403-7.

2. Steinberg W, Tenner S. Acute pancreatitis. N Engl J Med 1994;330:1198-210.

3. Bayne L, McLeod PJ, Ogilvie RI. Meyler's side effects of drugs. Amsterdam, Oxford Princeton: Excerpta Medica; 1980.

4. Rominger JM, Gutierrez JG, Curtis D. Methyldopa-induced pancreatitis. Am J Dig Dis 1978;23(8):756-8.

5. Warren SE, Mitas JA, Swerdlin AHR. Pancreatitis due to methyldopa: case report. Milit Med 1980;145:399-400.

6. Heide H, Haaft MA. Pancreatitis caused by methyldopa. Br Med J 1981;282:1981-2.

7. Johnston DH, Cornish AL. Acute pancretitis in patients receiving chlorothiazide. JAMA 1959;170:2054-56.

8. Herfort K. Effect of thiazide preparations on the pancreas. Gastroenterologia 1966;106:111-2.

9. Sharma P, Stein D. Acute pancreatitis and thiazides. Gastroenterology 1972;26(4):695.

10. Eland A, Puijenbrock EP, Sturkenboom MJC et al. Drug-associated acute pancreatitis: Twenty-one tears of spontaneous reporting in the Netherlands. Am J Gastroenterol 1999;9:2417-22.

11. Bergholm U, Langman M, Raulins M. Drug-induced acute pancreatitis. Pharmacoepidemiol Drug Safety 1995;4:329-34.

12. Meltzer HY. Clozapine and other atypical neuroleptics: efficacy, side effects and optimal utilization. J Clin Psychiatry 1994;12:38-42.

13. Buzan RD, Zibin T, Thomas M. Valproate associated pancreatitis and cholecystitis in six mentally retarded adults. Clin Psychiatry 1995;56:529-32.

14. Kvande KT, Madsen S. Selective serotonin uptake inhibitors and pancreatitis. Tidsskr Nor Laegeforen 2001;121(2):177-8.

None financial support and conflict of interests.

Received on 31/3/2003.

Approved on 24/7/2003.

Publication Dates

• Publication in this collection
  30 Mar 2004
• Date of issue
  Mar 2004

History

• Received
  31 Mar 2003
• Accepted
  24 July 2003