Catherine Frogley (UK) and team reviewed the evidence for Clozapine’s anti aggressive effect.
Why this question is important?:10 % of patients with schizophrenia or other psychotic disorders behave violently, compared to less than 2 % of the general public, with the risk of homicide up to 20 times higher (Fazel et al. 2009 ).In the inpatient setting, aggression is even more common with rates of assault by patients with schizophrenia between 16% and 28% (Joyal et al. 2008; Kru ̈ger & Rosema, 2010) .Up to 40% of patients will not respond favourably despite the sequential use of the rec- ommended doses for 6 to 8 weeks of at least two antipsychotics (NICE, 2010) and will meet criteria for ‘treatment resistance’ (Kane et al. 1996).
Results: Systematic Review shows that the majority of the studies that have investigated the effects of clozapine on violent behaviour in schizophrenia employed open-label or retrospective designs, with only four randomized controlled studies. Four RCTs included some consideration of clozapine’s anti-aggressive effects in schizophrenia (Citrome & Volavka, 2000 ; Glazer & Dickson, 1998 ; Topiwala & Fazel, 2011; Volavka & Citrome, 2008)
Authors Conclusion: The study data show that clozapine appears to offer an anti-aggressive effect in schizophrenia and psychosis, possibly greater than any other antipsychotic. This anti-aggressive effect is also seen in patients with other psychiatric disorders including emotionally unstable BPD, autistic spectrum disorders, post- traumatic stress disorder and learning disability, although the breadth and quality of data is even more circumspect.
Is it a specific Effect?: The majority of studies speculate, that at least some of clozapine’s anti-aggressive advantages were ‘ specific ’, i.e. independent both of its more generic antipsychotic and sedative effects. These conclusions were based primarily on the statistical independence of the results and secondly on observations that the reductions in violence exceeded the relatively modest improvements in psychotic symptom control and were temporally distinct and longer lasting than changes in sedation.
Problems :patient selection strategies were inconsistent across the studies, There are only 4 RCTS, definition of violence highly variable across studies,criteria of patient selection to Clozapine is not uniform.
Anti aggression How?: violence and aggression in schizophrenia are aetiologically heterogeneous, it is likely that clozapine exerts its anti-aggressive effects through a number of pathways . It might have specific advantage over other agents by 1. Reduce impulsivity 2. Increase adherence 3. Specific benefit on substance use 4. improvements in cognitive functions.
Clinical Practice: Clozapine is an effective antipsychotic for the treatment of psychotic symptoms and for the management of aggressive and violent behaviour in patients with schizophrenia, and other psychiatric disorders. Clozapine should always be considered as an option in this group of patients.
summary of the article:
Frogley C, Taylor D, Dickens G, Picchioni M. Int J Neuropsychopharmacol. 2012 Oct;15(9):1351-71