A systematic review of the evidence of clozapine's anti-aggressive effects

Abstract

Reducing the risk of violent and aggressive behaviour in patients with schizophrenia remains a clinical priority. There is emerging evidence to suggest that the second-generation antipsychotic, clozapine, is effective at reducing this risk in patients with schizophrenia and some evidence to suggest that it may be best in selected patients. We conducted a systematic literature search in March 2011 of all prospective and retrospective studies, which investigated clozapine's anti-aggressive effects in a variety of mental disorders. The review identified six animal studies, four randomized controlled trials, 12 prospective non-controlled studies and 22 retrospective studies, with four case studies. We found considerable evidence in support of clozapine's ability to reduce violent and aggressive behaviour. Clozapine's anti-aggressive effect was most commonly explored in patients with schizophrenia, with less evidence available for other psychiatric disorders, including borderline personality disorder, autistic spectrum disorders, post-traumatic stress disorder, bipolar disorder and learning disability. There was mixed evidence to address the question of whether or not clozapine was any more effective than other antipsychotics. In the case of schizophrenia, there was evidence to suggest that clozapine's anti-aggressive effect was more marked particularly in those with treatment-resistant illness. Its anti-aggressive effects appeared to be 'specific', being to some extent greater than both its more general antipsychotic and sedative effects. There were significant methodological inconsistencies in the studies we identified, particularly surrounding patient recruitment criteria, the definition and measurement of violence and the lack of randomized, controlled trials. Data on therapeutic monitoring were also limited. Clozapine can reduce violence and persistent aggression in patients with schizophrenia and other psychiatric disorders. It may offer an advantage over other antipsychotics, although perhaps exclusively in the case of traditionally defined 'treatment resistance' or more broadly defined 'complex cases' with co-morbidity. Larger, randomized, blinded, controlled studies with robust characterization of participants, and standardized measures of violence and aggression are, however, needed to fully understand this link and explore the possible mechanisms.

A Case of Drug-Induced Acute Dyskinesia Treated with Korean Medicine

“…It has also been suggested that earlier use (as a second line agent) can be recommended in individuals with persistent hostility/aggressive behaviour [47] and suicidalilty [39][40][41][42]. In fact the indication for recurrent suicidal behavior has been officially approved by the FDA [48].…”

“…Reasons for physicians' reluctance to prescribe clozapine have been evaluated and the relatively high incidence of agranulocytosis has certainly had great influence; however, the careful monitoring of WBC counts and ANC has almost completely abolished the risk of fatal agranulocytosis; frequency of blood tests has recently been simplified and once WBC counts and ANCs have been maintained within normal levels for one year, blood tests are now only required once every 4 weeks [27,47]. It is also of importance to note that in some European countries a more flexible monitoring schedule, which can be reduced to quarterly blood testing in individuals not at risk, has been proposed [59,60].…”

Pharmacobiological Treatments in Autism Spectrum Disorders

“…However, the major drawback of atypical antipsychotics are side effects such as weight gain, metabolic changes, sleep disturbances, higher risk of sedation and tremor, drooling, increased appetite, fatigue, dizziness, and withdrawal dyskinesias [29,30]. Another atypical antipsychotic drug, clozapine, has been shown to be effective against hyperactivity and aggression in children with ASD [31].Therefore, based on limited evidence with small sample sizes and short follow-ups, atypical antipsychotics may be more effective as short-term interventions for certain behavioral symptoms in patients with ASD.…”

Violence in Schizophrenia

“…Dolayısıyla şizofreni hastalarında şiddete giden yol çokludur ve bu sebepsel karmaşıklık tedavide de önem sergilemektedir. [47] Şiddet Olgusuna Akut Yaklaşım www.cappsy.org Öncelikle güvenlik sağlanmalı, tehlikeli olabilecek eşyalar uzaklaştırılmalıdır. Hastaya karşı saygılı, empatik ve ilgili bir tutumla görüşme yapılmalıdır.…”

“…[13,55] Olanzapinin; haloperidol, ketiyapin ve amisulpirid ajanlarının şiddet azaltıcı etkinliğine olan üstünlüğü bildirilmiş-tir. [47] Yapılan çalışmalarda, risperidonun şiddet davranışını azaltıcı etkisi bildirilmiş-tir. [56,57] Randomize çift-kör uygulanmış bir çalışmada şizofreni tanılı hastalarda şiddet davranışını azaltmakta plaseboya üstünlüğü gösterilmiştir.…”