Published on BCNC website 16th of January 2008
Increased Aggressive, Violent, and Impulsive Behaviour in Patients During Chronic-Prolonged Benzodiazepine Use
Can J Psychiatry. 2000 Feb;45(1):89-90
VM Mathew, MD, Phil, MRCPsych
SM Dursun, MD, PhD, FRCPC
MA Reveley, MD, PhD, FRCPsych
Leicester, United Kingdom
There is evidence that suicidal, aggressive, and impulsive behaviours are linked to putative dysregulation in central 5-hydroxytryptamine (c5HT) systems. Regardless of the underlying mechanisms, low serotonergic (5HTergic) functioning may be associated with increased vulnerability to a range of psychiatric disturbances, especially suicidal, aggressive, violent, hostile, antisocial, and impulsive behaviour (1). Indeed, c5HT systems are crucially involved in the control of aggressive behaviour in humans. For example, it has been shown that patients with low CSF 5-hydroxyindoleacetic acid (5HIAA) scored significantly higher in hostility (2). Asberg and coworkers demonstrated that suicide acts, but not suicide ideation, are related to a low CSF 5HIAA (1).
There is evidence that both acute and chronic administration of benzodiazepines (BZD) decrease c5HT neurotransmission (3,4). It would therefore be predicted that chronic BZD use may induce aggressive and impulsive behaviour. Indeed, there is some evidence that some BZD especially chlordiazepoxide and oxazepam enhance aggressive and violent behaviour (5,6). Gardos and others report an increase in verbal hostility in healthy volunteers medicated with chlordiazepoxide, but not with oxazepam (6). In another study, compared to diazepam, oxazepam caused fewer episodes of enhanced aggression in a prison population (7). Therefore, in this exploratory and retrospective chart-review study, we investigated the hypothesis that decreased 5HTergic neurotransmission by chronic BZD use may increase aggressive and impulsive behaviour. Patient charts were randomly selected, and the diagnosis of anxiety disorder was based on these files. Patients with a premorbid history of violent and criminal acts (forensic history), chronic alcoholism, and drug addiction were excluded from this study. Fifty-eight patients (14 male [age range = 32-68 years: mean ± SD = 49.2 ± 2.3 years]; 44 female [age range = 23-84 years: mean ± SD = 51.5 ± 1.87 years]) who were prescribed various BZD with a wide-dose range, (lorazepam: 22; diazepam: 20; chlordiazepoxide: 13; temazepam: 2; oxazepam: 1 patients) for a varying period of time (range = 5-43; mean ± SD = 21.7 ± 1.15 years with regular and/or irregular periods) were compared to 58 patients (14 male [age range = 30-70 years: mean ± SD = 48.8 ± 3.2 years]; 44 female [age range = 23-83 years: mean ± SD = 50.6 ± 1.9 years] duration of the illness range 5-55 years: mean ± SD= 20.1% 1.4) who received only behavioural psychotherapy. Aggressive, impulsive, and violent behaviour were recorded by a standard questionnaire from the progress notes. Statistical analysis (Fisher's Exact test, P 0.001) demonstrated that the BZD group was more likely to develop aggressive, impulsive, and violent behaviour than were the patients who received behavioural psychotherapy. Within the BZD group, 53.5% of the patients showed aggressive, impulsive, or violent behaviour whereas only 5.1% of the patients who received psychotherapy showed such behaviours. These results suggest that chronic and prolonged BZD use may increase impulsive behaviour. Alternatively, one might suggest that behavioural psychotherapy more effectivly reduced impulsivity. However, since patients with premorbid impulsivity were excluded, we suggest that BZD-induced impulsivity may be a more likely explanation and that low c5HT neurotransmission is the underlying mechanism. Prospective-controlled studies are required to confirm our data; in the meantime, patients with a premorbid history or susceptibility to impulsivity should be closely monitored if they are prescribed BZD, and long-term prescription should be avoided.
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