Hematological Effects of Atypical Antipsychotics (AAPs) in a Geriatric Population: What is the Role of 5-HT2 Receptors

NCT06107322 | Unknown

• 1 other identifier: 8902
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

White lineage abnormalities and in particular neutropenia and agranulocytosis are known and increasingly studied adverse effects of antipsychotics, particularly second generation. White lineage abnormalities have been found with each of the drugs in this class even if progression to agranulocytosis is rarer with drugs other than Clozapine. The infections, sometimes serious, induced by these adverse effects have largely led to limiting the use of second generation antipsychotics, and in particular clozapine, to the treatment of patients resistant to other first or second line treatments. Several hypotheses have been put forward: the first is that of an immuno-allergic reaction mediated by eosinophils with increased sensitivity depending on the HLA type, another that of a direct toxic effect of clozapine or its main metabolite, N -demethylclozapine and a third attributes hematological disorders to catecholaminergic inhibition which prevents the differentiation of CD34+ hematopoietic stem cells into leukocytes, after blocking dopaminergic and/or beta-adrenergic receptors. More recently, a new hypothesis is emerging following scandals particularly in France linked to Benfluorex (Mediator®), Dexfenfluramine (Isomeride®) and Fenfluramine (Pondéral®). Indeed, by studying the cellular mechanisms linked to the stimulation of the 5-HT2B receptor by their common metabolite Nordexfenfluramine, researchers from the NeuroCardiovascular pharmacology and toxicology laboratory in Strasbourg have demonstrated that the stimulation of 5-HT2BR mobilizes CD34+ cells in blood from the bone marrow and selective blocking of 5-HT2B receptors, reduces the number of leukocytes in the blood, mainly neutrophils and lymphocytes, further decreasing their blood concentration with exposure time.

Conditions

Neutropenia

Keywords

Neutropenia; Atypical antipsychotics (AAPs); 5-HT2 receptors; Hematological effects

Outcome Measures

Primary Outcomes (1)

• Number of neutrophils per liter of blood

  1 hour after blood collection

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Age Groups: Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Major subject (≥ 65 years old) having indication for the introduction of the neuroleptic indicated

You may qualify if:

• Major subject (≥ 65 years old)
• Subject hospitalized in Geriatric Internal Medicine, in Geriatric Follow-up Care and Rehabilitation, in a Long-Term Care Unit or Important Medical-Technical Care, in a Reinforced Accommodation Unit or in a Cognitive-Behavioral Unit at Strasbourg University Hospitals)
• Subject not opposing the reuse of their data for the purposes of this research.
• Indication for the introduction of the neuroleptic indicated
• Available dosage and frequency of administration and duration of treatment

You may not qualify if:

• Subject having expressed opposition to participating in the study
• Presence of a neuroleptic before admission to the University Hospitals of Strasbourg, excluding readmission of a patient included
• Neuroleptics not present on the discharge prescription for long-term treatment
• Neuroleptics prescribed for less than 48 hours
• Presence of a white lineage anomaly prior to the initiation of neuroleptic treatment
• Patient contraindicated for taking a long-term neuroleptic.
• Hematological disease with white lineage abnormality (lymphoma, leukemia, myelodysplasia, mye syndrome

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (1)

Service de Pharmacie - Stérilisation - CHU de Strasbourg - France

Strasbourg, 67091, France

RECRUITING

MeSH Terms

Conditions

Neutropenia

Condition Hierarchy (Ancestors)

Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Central Study Contacts

Estelle AYME-DIETRICH, Pharm, PhD

CONTACT

33 3 68 85 30 83; estelle.ayme@chru-strasbourg.fr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2023
• First Posted: October 30, 2023
• Study Start: March 1, 2023
• Primary Completion: March 1, 2024
• Study Completion: March 23, 2024
• Last Updated: October 30, 2023

Record last verified: 2023-10

Locations

FR (1)