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Bonelli, RM; Hofmann, P; Aschoff, A; Niederwieser, G; Heuberger, C; Jirikowski, G; Kapfhammer, HP.
The influence of psychotropic drugs on cerebral cell death: female neurovulnerability to antipsychotics.
INT CLIN PSYCHOPHARMACOL. 2005; 20(3): 145-149. Doi: 10.1097%2F00004850-200505000-00004
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Leading authors Med Uni Graz
Bonelli Raphael
Co-authors Med Uni Graz
Hofmann Peter
Kapfhammer Hans-Peter
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Abstract:
Tissue transglutaminase (tTG) is a marker for apoptosis, and its protein level is known to be increased in post-mortem Alzheimer's and Huntington's disease brains. tTG is increased in the cerebrospinal fluid of patients with Alzheimer's disease. However, the influence of psychotropic medication on acute cell death has not been studied so far in vivo, although some experiments performed in vitro suggest that antipsychotic drugs are neurotoxic. The protein level of tTG was examined in the cerebrospinal fluid obtained from 29 patients under neuroleptic medication in the last 24 h before lumbar puncture (eight patients diagnosed with Alzheimer's disease and 21 patients with other neurological diseases), and compared with those from 55 patients without antipsychotic medication (25 Alzheimer's patients and 30 others). In addition, the influence of several other psychotropic drugs on apoptosis was analysed. A significant influence (P<0.01) of antipsychotic drugs for both the Alzheimer's and the non-Alzheimer's group was found with respect to tTG protein levels in cerebrospinal fluid. By contrast to the male subgroups, the female groups showed a strong influence of neuroleptics on cerebral cell death. Surprisingly, atypical antipsychotics did not differ from typical neuroleptics in neurotoxicity. By contrast, no influence of antidepressants, cholinesterase-inhibitors, nootropics, tranquilizers and tramadol on cerebral cell death was found. The results suggest that typical and atypical antipsychotic drugs may induce cerebral cell death, especially in female patients. Subjects with Alzheimer's disease might be even more vulnerable to any antipsychotic. Therefore, subsequent research should aim to identify atypical neuroleptics without neurotoxicity. A limit on the use of first- and second-generation antipsychotics in elderly patients is proposed. Finally, the possible connection between the observed increased cerebral cell death and tardive dyskinesia, the most threatening side-effect in antipsychotic therapy, is discussed.
Find related publications in this database (using NLM MeSH Indexing)
Aged -
Aging - physiology
Alzheimer Disease - cerebrospinal fluid
Antipsychotic Agents - adverse effects
Apoptosis - drug effects
Biological Markers - drug effects
Brain - pathology
Female - pathology
Humans - pathology
Male - pathology
Middle Aged - pathology
Psychotropic Drugs - adverse effects
Retrospective Studies - adverse effects
Sex Characteristics - adverse effects
Transglutaminases - cerebrospinal fluid

Find related publications in this database (Keywords)
Alzheimer's disease
antipsychotic drugs
apoptosis
neurotoxicity
tardive dyskinesia
tissue transglutaminase
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