Chlorprothixene 50mg tablets

IntroductionSupratherapeutic exposures to pharmaceuticals are a considerable cause of seizures, often leading to severe complications. This study aimed to identify the drugs most frequently associated with seizures in overdose and to evaluate their seizure potential, focusing on dosage and age-related differences.MethodsA retrospective analysis of single-agent pharmaceutical exposures, mostly overdoses, reported to Tox Info Suisse from 1 January 2011 to 31 December 2023 was conducted. Cases with seizures were compared to all cases ("seizure rate") and to all cases involving the same substance ("seizure potential"). The median ingested dose was compared to the maximum approved daily dosage ("relative overdose"), and relative overdose in seizure versus non-seizure cases with the same substance was compared ("seizure overdose ratio").ResultsThere were 20,176 single-agent pharmaceutical exposures, with seizures reported in 233 cases (1.2%). Antidepressants were the most frequently implicated drug class (34.3%). Mefenamic acid (15.7%), quetiapine (10%), and bupropion (10%) were most commonly associated with seizures. Cefepime (37.5%) and bupropion (23.7%) showed the highest seizure potentials. Seizures occurred at low relative overdoses for clozapine, chlorprothixene, and trimipramine (1.3×, 2.0×, 2.8×, respectively). Tricyclic antidepressants (notably trimipramine), mefenamic acid, tolperisone, and bupropion exhibited low seizure overdose ratios (1.4, 2.0, 2.1, 2.1, respectively). Age-related seizure rates did not differ significantly between adolescents (1.7%) and adults (1.5%).DiscussionBesides the established seizure association of antidepressants, this analysis confirmed the high seizure risk of overdoses of mefenamic acid and bupropion. A comparative assessment using relative overdoses and seizure overdose ratios revealed that even mild overdoses of clozapine or chlorprothixene induce seizures. For mefenamic acid, tolperisone and bupropion, seizures occurred at overdoses only about twice those not associated with seizures. Seizures from intravenously administered cefepime were caused by not adapting the posology to decreased kidney function.ConclusionOverdoses of mefenamic acid, quetiapine, bupropion, venlafaxine and tramadol, respectively, were most commonly associated with seizures. Cefepime exhibited the highest seizure potential, in patients with impaired renal function. Tricyclic antidepressants (trimipramine, amitriptyline), tolperisone, mefenamic acid and bupropion were associated with seizures at relatively small overdoses compared to respective non-seizure cases.

Abstract licence: CC BY

Introduction: Chlorprothixene is a typical antipsychotic, primarily used in the treatment of psychotic disorders. Overdose may result in severe cardiovascular and central nervous system toxicity. Evidence on the effectiveness of extracorporeal elimination is scarce. Case Presentation: A 19-year-old female ingested 5 g of chlorprothixene in a suicide attempt. Upon admission to the intensive care unit, she was awake, responsive, and oriented. Initial management included 50 g of activated charcoal. As doses of >2 g chlorprothixene can cause severe intoxication and death, attempts to enhance drug elimination by extracorporeal therapy were undertaken. Therapeutic plasma exchange (TPE) was initiated approximately 3 h after admission, exchanging 5,096 mL of plasma with albumin solution and FFP over 3 h 10 min. This was followed by a 10 h 10 min prolonged intermittent kidney replacement therapy (PIKRT). Serial blood, apheresis, and dialyzate samples were collected to quantify drug removal. Both procedures were well tolerated. The patient remained clinically stable and was transferred to a psychiatric facility 24 h post-admission. Conclusion: Although chlorprothixene plasma levels decreased, the amount of chlorprothixene removed by TPE and PIKRT was negligible, classifying the drug as “not dialyzable” per EXTRIP criteria. Given the limited clinical evidence and the pharmacokinetic properties of chlorprothixene, TPE cannot be recommended for the management of chlorprothixene overdose and should not be regarded as a standard treatment option. According to the available literature, this is the first description of chlorprothixene intoxication managed with both TPE and high-flux hemodialysis, highlighting the limited extracorporeal removal of this drug.

Abstract licence: CC BY-NC 4.0

Abstract Treatment with antipsychotics such as chlorprothixene, clozapine, olanzapine and quetiapine can be associated with cardiovascular and metabolic risks and poisoning, making them highly relevant in toxicological investigations. Since antipsychotics primarily act within the central nervous system, brain tissue serves as an alternative or complementary matrix to femoral blood in toxicological analysis. This study aimed to retrospectively evaluate brain concentrations and brain-blood ratios across toxic and non-toxic levels in 466 postmortem cases involving chlorprothixene, clozapine, olanzapine and/or quetiapine. Median concentrations in brain tissue across all cases were 0.20 mg/kg for chlorprothixene, 4.2 mg/kg for clozapine, 0.42 mg/kg for olanzapine and 0.34 mg/kg for quetiapine. Corresponding brain-blood ratios remained stable across the examined concentration range with median ratios of 3.1 for chlorprothixene, 2.9 for clozapine, 2.6 for olanzapine and 3.0 for quetiapine. The provided brain concentrations and ratios can support further toxicological evaluations of postmortem cases.

Abstract licence: CC BY 4.0