Sulpiride induced agranulocytosis: a case report

ISSN 2397-5628 Journal of Geriatric Care and Research 2018, Vol 5, No 2 Case report Sulpiride induced agranulocytosis: a case report Deepak Kumar Shukla, Pravija Talapan Manikoth Abstract Sulpiride is an antipsychotic medication which is used commonly by some clinicians to treat schizophrenia and psychosis. It is prescribed both in out-patients clinic as well as on the wards. Sulpiride induced leucopenia is rare. Clinicians prescribing sulpiride do not routinely check for this side effect. The mortality from drug induced agranulocytosis is reported to range from 5-10%. In this case report, we describe an 80 year old woman treated with sulpiride, who developed leucopenia within a week of commencing treatment. If leucopenia is not detected promptly, it can progress to agranulocytosis. Although a rare side effect, clinicians prescribing sulpiride need to be aware of this potentially life threatening side-effect. Repeating full blood count within a week of prescribing sulpiride could be worthwhile. Unexplained fever or infection following treatment with sulpiride should prompt immediate haematological investigations. Key words Agranulocytosis, leucopenia, side effect, sulpiride, Introduction Agranulocytosis induced by antipsychotic drugs especially clozapine is well known; hence clozapine therapy requires mandatory monitoring of white blood cells and absolute neutrophil count.1 Leucopenia or agranulocytosis induced by sulpiride is very rare. This case report is about sulpiride induced leucopenia which was discovered incidentally during a routine blood test. symptoms. She was previously well and functioning independently. Preceding the mental health referral, she was evaluated by the medical team for worsening confusion. Her preliminary blood investigations showed raised liver enzymes (alkaline phosphatase 758 U/L and ALT 372 U/L), the cause of which was unclear. Full blood count (FBC) showed a raised white cell count (WCC) (13.2 × 109/L) which declined spontaneously to 7.7 × 109/L in six days and remained stable thereafter (7.8 × 109/L, a week later). A subsequent liver ultrasound scan was reported as normal. Electrocardiogram (ECG) showed prolonged QTc (484msec); blood tests did not demonstrate any electrolyte abnormalities that could have caused this. There was no history of blood dyscrasias. The patient had a background history of myocardial infarction two months earlier. Due to concerns over her liver function, her medication for hypercholesterolemia (atorvastatin) was discontinued. She was commenced on sertraline for low mood and was referred for further psychiatric evaluation. On initial assessment, the patient displayed low mood, psychomotor retardation, loosening of association of thoughts and a limited insight into her mental health difficulties. She expressed persecutory delusions and delusions of guilt. Auditory hallucinations were also reported. She became poorly compliant with medications and was refusing to have blood tests. Therefore, she was placed on compulsory admission under the Mental Health Act (Section 2), and was commenced on aripiprazole 2.5mg per day, whilst continuing sertraline. Case history The patient became increasingly restless and agitated on aripiprazole hence this was discontinued. In view of a history of myocardial infarction, prolonged QTc and abnormal liver function, and intolerance with aripiprazole, the available treatment options were discussed within the treating team including the pharmacist. Following discussion and agreement with the patient, she was started on sulpiride 100mg once daily initially, which was increased to 150mg once daily around five days later. Her medical treatment for cardiovascular co-morbidities included perindopril, bisoprolol, lansoprazole, aspirin and ticagrelor. An 80 year old Caucasian lady was referred to Old Age Psychiatry by the acute medical team due to ongoing concerns regarding depressive as well as psychotic The patient demonstrated a substantial improvement in mental state on sulpiride, with a prompt resolution of psychotic symptoms and improvement in mood. Eight Sulpiride is an antipsychotic medication which belongs to the substituted benzamide group. It is indicated in schizophrenia and it acts as a selective antagonist at the dopamine D2 and D3 receptors. In this case report we have highlighted that clinicians need to be careful when prescribing sulpiride and ensure that patients are closely monitored for this potential side effect. 68 Shukla and Manikoth, 2018 days into the treatment with sulpiride, her admission status was re-graded as voluntary (informal) because she expressed willingness to engage with the treatment plan. The FBC was rechecked on day 8; results showed leucopenia with a WCC of 1.8 × 109/L and neutrophil count of zero. The patient was asymptomatic from a medical perspective. Following a comprehensive discussion with the haematology team, a conclusion of sulpiride induced agranulocytosis was made and the drug was discontinued. The patient received three subcutaneous injections of granulocyte colony stimulating factor (G-CSF) 300 micrograms on alternate days. Her WBC and neutrophil count came back to normal values two days after the first injection of G-CSF. After this, the patient was prescribed olanzapine. She was also given electroconvulsive therapy (ECT) following a review and approval from the cardiology team. The patient responded well to a total of eight ECT treatment sessions. Her mental state improved and she became euthymic. She was subsequently discharged from the unit after four months of inpatient stay. Discussion induced by proton pump inhibitors (omeprazole and esomeprazole) however a genetic mutation was considered to be associated.5 However in the case described in this report, she continued to have lansoprazole before without any agranulocytosis. Besides, following discontinuation of the sulpiride the blood counts returned to normal levels, suggestive of possibility of the associations of sulpiride with the agranulocytosis. Conclusion It appears that leucopenia and neutropenia are rare side effects of sulpiride. However considering their seriousness, these rare side effects should be kept in mind and caution should be exercised while prescribing sulpiride. FBC monitoring may be considered, especially if there are suggestive symptoms. Author information: Deepak Kumar Shukla, MBBS, Diploma in Clinical Psychiatry, MRCPsych, Heath Lane Hospital, Heath Lane, West Bromwich B71 2BG, UK, Email: deepak.shukla@nhs.net; Pravija Talapan Manikoth, MBBS, MRCPsych, Consultant in Old Age Psychiatry, Edward Street Hospital, Edward Street, West Bromwich B70 8NN, UK, Email: pravijatm@doctors.org.uk Correspondence: Deepak Kumar Shukla, Heath Lane Hospital, Heath Lane, West Bromwich B71 2BG, UK, Email: deepak.shukla@nhs.net Competing interests: None. The authors received no financial support. This patient had deranged liver function test as well as a history of recent cardiovascular event hence sulpiride was commenced considering it as a safer option. It is also known that sulpiride has a low effect on the QTc interval. She was tried on other antipsychotic medication but her liver function was getting worse. Her physical health was being closely monitored considering co-morbidities and because of the reduced food and fluid intake. The baseline blood investigations were repeated on a routine basis and FBC showed agranulocytosis. She had no symptoms suggestive of agranulocytosis. There were no obvious causes for the agranulocytosis; except the possible side effect of suliride which was recently prescribed. Once sulpiride was discontinued and she was commenced on GCSF, WBC count improved quickly. Her LFT too gradually improved. Sulpiride induced leucopenia or agranulocytosis is rare and hence a yellow card (British National Formulary) was submitted.2 Many medications are reported to be associated with agranulocytosis. King and Wagner analysed surveillance data for reports of haemopoietic disorders with 16 antipsychotics in common use.3 They found no evidence of any increased risk with high-potency drugs such as haloperidol or pimozide or with the newer drugs such as sulpiride or risperidone. A systematic review of agranulocytosis induced by non-chemotherapy drugs did not find any evidence about sulpiride causing agranulocytosis.4 There is a case report of agranulocytosis Received: 28 June 2018; Revised: 11 October 2018; Accepted: 12 October 2018 Copyright © 2018 The Author(s). This is an open-access article distributed under the terms [CC BY-NC] which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Citation: Shukla DK Manikoth PT. Sulpiride induced agranulocytosis: a case report. Journal of Geriatric Care and Research 2018, 5(2): 68-69. References 1. Kar N, Barreto S, Chandavarkar R. Clozapine monitoring in clinical practice: Beyond the Mandatory Requirement. Clin Psychopharmacol Neurosci. 2016; 14(4):323-329. 2. https://yellowcard.mhra.gov.uk/the-yellow-card-scheme/ [cited 2018 October 11] 3. King DJ; Wager E. Haematological safety of antipsychotic drugs. Journal of psychopharmacology (Oxford, England); 1998; vol. 12 (no. 3); 283-288. 4. Andersohn F, Konzen C, Garbe E. Agranulocytosis induced by nonchemotherapy drugs; a systematic review. Ann Intern Med. 2007; 146(9):657-65. 5. Dury S, Nardi J, Gozalo C, Lebargy F, Deslee G. Agranulocytosis induced by proton pump inhibitors. J Clin Gastroenterol. 2012; 46(10):859. 69