Abstract
Valproate-induced acute pancreatitis is a rare, potentially life-threatening idiosyncratic adverse effect. Although most reports involve children treated for epilepsy, adults with bipolar disorder may also be affected. We describe such a young woman in sustained remission on valproate who developed acute necrotising pancreatitis, improved after prompt discontinuation and conservative management, and remained stable after switching to lithium, with no recurrence over 30 months of follow-up. This case highlights the importance of early recognition, immediate drug withdrawal, and coordinated cross-disciplinary planning to ensure both clinical recovery and ongoing mood stability.
Case report
A 24-year old woman, with a five-year history of bipolar affective disorder (in sustained remission) and hypothyroidism, presented with three days of severe epigastric pain radiating to the back, worsened with oral intake, with vomiting and features of ileus and no history of alcohol use, prior pancreatitis, gallstone disease, hypertriglyceridaemia, or recent infection. She had been taking sodium valproate 750 mg od for approximately two years (serum valproate levels 97 μg/mL; normal 50–100 μg/mL).
On admission, vital signs were stable and there was no jaundice or cardiopulmonary compromise. Blood investigations showed leukocytosis (20 × 109/L), markedly elevated C-reactive protein (127 mg/L) and raised pancreatic enzymes (amylase 710 U/L; lipase 305 U/L). Liver function tests were not suggestive of biliary obstruction; calcium and triglycerides were within normal range. Abdominal ultrasonography showed a bulky heterogeneous pancreas without biliary disease. Contrast-enhanced computed tomography demonstrated marked peripancreatic inflammatory changes with <30% pancreatic necrosis.
Given the exclusion of common aetiology and her medication exposure, valproate-associated pancreatitis was considered the most plausible cause. Thus valproate was discontinued on admission, and our patient was monitored for mood or behavioural change during medical treatment. Conservative management was pursued with intravenous fluids, analgesia, antiemetics, and close monitoring. Pain and ileus improved within 72 h, and she tolerated oral intake. She was then discharged aftersix days with explicit documentation to avoid future valproate exposure.
After her medical stabilisation, lithium was initiated as an alternative maintenance mood stabiliser with regular monitoring. Over the 30 months of liaison psychiatry outpatient follow-up, she remained euthymic with good socio-occupational functioning on lithium 900 mg/day (most recent level 0.72 mmol/L; therapeutic maintenance range 0.6–1.0 mmol/L), with stable renal and thyroid parameters and no recurrence of pancreatitis.
Discussion
Valproate-associated pancreatitis appears idiosyncratic and can occur despite therapeutic dosing and typical serum levels. 1 Potential mechanisms include oxidative injury and mitochondrial dysfunction, but no predictive clinical marker exists. 1 Therefore, new severe epigastric pain with vomiting in a patient taking valproate should prompt immediate evaluation; as the presentation is clinically indistinguishable from other causes, clinicians should stop valproate promptly while investigations proceed.
In our patient, causality was supported by temporal association, exclusion of competing causes and improvement after discontinuation consistent with a probable adverse drug reaction (Naranjo score 7). 2 Factors such as patient age, valproate dose or serum levels do not appear to predict the onset or outcome of pancreatitis. 1 Though our patient improved rapidly with conservative management, fatal outcomes up to 16%, particularly in necrotising cases, have been reported. 1 Prior reports caution strongly against rechallenge given high recurrence rates and worse outcomes in necrotising presentations. 1
Another key management issue in our case was preventing the bipolar disorder relapse after abrupt cessation of an effective mood stabiliser. After medical stabilisation, lithium was initiated as a guideline-supported maintenance treatment. 3 Unlike valproate, lithium is not a well-established cause of pancreatitis and can be used with routine renal and thyroid monitoring.3,4 Our patient has maintained sustained remission without pancreatitis recurrence over the course of more than two years. This longitudinal follow-up is clinically useful because many reports lack long-term psychiatric and medical outcomes.
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Footnotes
Ethical consideration
Patient's and family members’ written informed consent was taken prior to writing this report.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.