ArticleBMC psychiatry2023
Valproate-related neutropenia and lithium-related leukocytosis in patients treated with clozapine: a retrospective cohort study.
Article in BMC psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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14 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Risk factors associated with blood dyscrasia during clozapine treatment: a systematic review and meta-analysis.Psychological medicine · 2026Pooled it
- Late-Onset Neutropenia in Clozapine Users: Unrelated or Drug-Induced? A Case-Registry Analysis of Incidence, Characteristics, and Rechallenge Attempts.Schizophrenia bulletin · 2026Article
- Clozapine for treatment-resistant schizophrenia with epilepsy: A case report.PCN reports : psychiatry and clinical neurosciences · 2026Article
- Modulatory effects of valproic acid and UGT polymorphisms on norclozapine plasma levels in clozapine-treated patients with schizophrenia.Scientific reports · 2026Article
- Assessment of the biological efficacy of gold Nannochloropsis oculata nano-extract against lithium-induced toxicity in rats.Scientific reports · 2026Article
- Application of a Nomogram Model in Predicting Postoperative Delirium Following Percutaneous Coronary Intervention.Bioengineering (Basel, Switzerland) · 2025Article
- Evaluating Reduced Blood Monitoring Frequency and the Detection of Hematological Abnormalities in Clozapine-Treated Patients With Schizophrenia: A Chart Review Study From the COVID-19 Pandemic.Schizophrenia bulletin · 2025Article
- Case Report: From lung to peritoneum: genomic and immunologic insights into a rare dual-siteFrontiers in immunology · 2025Article
- Significant haematological alterations in clozapine-treated patients: prevalence and clinical correlation.Acta neuropsychiatrica · 2024Article
- Review
- Decoding Clozapine-Induced Agranulocytosis: Unraveling Interactions and Mitigation Strategies.Pharmacy (Basel, Switzerland) · 2024Article
- Can lithium be used in the setting of clozapine commencement in patients with COVID-19 associated neutropenia: A case report.Clinical case reports · 2024Article
- Article
- Data Mining for Risks of Clozapine Side Effects, Including Neutropenia, Associated with Lithium Carbonate Administration: Analysis Using the Japanese Adverse Drug Event Report Database.Drugs - real world outcomes · 2023Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeutropenia is a noteworthy side effect of clozapine, which might warrant this drugs' discontinuance for safety. Studies have revealed that the risk of neutropenia increases with concurrent administration of valproate, but the evidence was limited. Conversely, lithium may have an ameliorating effect on clozapine-induced neutropenia. This study explored the effects of valproate and lithium on white blood cell counts in patients treated with clozapine.
methodsWe retrospectively investigated the electronic medical records from one tertiary psychiatric hospital in Taiwan and enrolled patients discharged between January 1, 2006, and December 31, 2017, with clozapine prescriptions. We scrutinized their demographic data, medications, and hematological results at discharge and during follow-up outpatient clinic visits over the subsequent 3 years. Patients were classified into four groups: clozapine only (CLO), clozapine and valproate (CLO + VAL), clozapine and lithium (CLO + Li), and clozapine, valproate, and lithium (CLO + VAL + Li). We also identified hematological events (neutropenia or leukocytosis) of these patients during outpatient follow-ups.
resultsOf the included 1084 patients, 55(5.1%) developed neutropenia. Concurrent valproate use (odds ratio [OR] = 3.49) and older age (p = .007) were identified as risk factors. Moreover, 453 (41.79%) patients developed leukocytosis. Younger age; male sex; and concurrent use of lithium (OR = 3.39, p < .001), clozapine daily dosage, and benzodiazepines were the risk factors for leukocytosis.
conclusionConcurrent valproate use and older age are associated with the development of neutropenia in patients treated with clozapine. Concurrent lithium usage, younger age, male sex, and concurrent benzodiazepine use might be related to leukocytosis.
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