title: Flunitrazepam: psychomotor impairment, agitation and paradoxical reactions.
abstract: Benzodiazepines are sedatives used for anxiolysis, hypnosis, muscle relaxation and the treatment of epilepsy. Paradoxical reactions including agitation, talkativeness, confusion, disinhibition, aggression, violent behavior and loss of impulse control may, however, occur in some subjects. It has been claimed that high doses of flunitrazepam may cause aggression on a more regular basis in all individuals. The present study makes use of a Norwegian forensic toxicological database containing analytical results from drivers suspected of driving under the influence and suspects of violent crime to analyze the relationship between behavior and blood flunitrazepam concentration. Four-hundred and fifteen cases of drivers suspected of driving under the influence and seven cases of suspects of violent crime were studied. These selected cases had flunitrazepam as the only drug in blood samples and had been evaluated by a clinical test for impairment (CTI) performed by a police physician at the time of blood sampling. The impaired drivers had higher blood flunitrazepam concentrations than the not impaired drivers. Multivariate analysis revealed that both blood flunitrazepam concentration and age of the suspected drivers had independent impact on impairment, indicating tolerance with age. Most of the effects measured were sedative effects of flunitrazepam and these effects were related to flunitrazepam level. Possible paradoxical reactions were observed in a subgroup of 23 individuals (6%), but these reactions did not relate to blood flunitrazepam concentration. The suspects of violent crime showed similar degree impairment and had not more paradoxical reactions than the suspected drugged drivers. The findings were in agreement with other research that claims paradoxical reactions should be viewed as a reaction in certain individuals, and does not support the notion that flunitrazepam in high concentration produces aggression in all individuals taking the drug.
authors.affiliation: Norwegian Institute of Public Health, Department of Pharmacoepidemiology, PO Box 4404, Nydalen, NO-0403 Oslo, Norway. jorgen.bramness@labmed.uio.no
authors.forename: Jørgen G
authors.initials: JG
authors.lastname: Bramness
authors.forename: Svetlana
authors.initials: S
authors.lastname: Skurtveit
authors.forename: Jørg
authors.initials: J
authors.lastname: Mørland
mesh_terms: D000328:Adult; D000374:Aggression; D014151:Anti-Anxiety Agents / Q000009:adverse effects* / Q000097:blood; D001334:Automobile Driving / Q000706:statistics & numerical data*; D019955:Conduct Disorder / Q000097:blood / Q000453:epidemiology* / Q000209:etiology / Q000523:psychology; D003415:Crime / Q000706:statistics & numerical data; D016208:Databases, Factual; D005260:Female; D005445:Flunitrazepam / Q000009:adverse effects* / Q000097:blood; D005555:Forensic Psychiatry; D006801:Humans; D008297:Male; D009664:Norway / Q000453:epidemiology; D019966:Substance-Related Disorders / Q000097:blood / Q000453:epidemiology* / Q000209:etiology / Q000523:psychology; D014754:Violence / Q000706:statistics & numerical data*
chemical_list: D014151:Anti-Anxiety Agents; D005445:Flunitrazepam