Epidemiology
The groundbreaking epidemiological study that firmly established
the link between violence and schizophrenia determined one-year prevalence of
violent behavior in schizophrenia as 8.4%, compared with 2.1% in persons
without any disorder. The study has also reported clearly indicated that the
risk of violence is further increased by comorbid substance use disorders.
Swanson’s study was conducted in the United States. Many subsequent
epidemiological studies done in various countries have confirmed and expanded
Swanson’s original findings (Volavka 2002).
A meta-analysis of 20 studies compared risks of violence in 18,423
patients diagnosed with schizophrenia and other psychoses with general
population. There was a modest but statistically significant increase of risk
of violence in schizophrenia with an odds ratio of 2.1 (95% confidence interval
[CI] 1.7–2.7) without comorbidity, and an OR of 8.9 (95% CI 5.4– 14.7) with
comorbidity with substance abuse. Risk estimate of violence in individuals with
substance abuse (but without psychosis) showed an OR of 7.4 (95% CI=4.3-1)
(Fazel et al.,2009).
A study analyzed data from the National Epidemiologic Survey on
Alcohol and Related Conditions (NESARC), a two-wave project (N = 34,653: Wave
1: 2001-2003; Wave 2: 2004-2005). Indicators of mental disorder in the year
prior to Wave 1 were used to examine violence between Waves 1 and 2 (Elbogen et al., 2009). Surprisingly, severe
mental illness did
not independently predict future violent behavior.
Comorbid substance use disorder was one of the independent
predictors. However, we argued that the Elbogen analyses could be improved and
consequently we re-analyzed the same NESARC data (Van Dorn et al.,2012). We found that individuals with severe mental illness,
irrespective of substance abuse status, were significantly more likely to be
violent than those with no mental or substance use disorders. Those with
comorbid mental and substance use disorders had the highest risk of violence.
Historical and current conditions were also associated with violence, including
childhood abuse and neglect, household antisocial behavior, binge drinking and
stressful life events (Van Dorn et al.,2012).
Thus, substance abuse is a very important risk factor for violence in
schizophrenia. However, the weight of evidence suggests that features of
schizophrenia such as psychotic symptoms and comorbid personality disorders
are also likely to be independent risk factors for violence in
individuals with schizophrenia (Volavka & Swanson 2010).
Clinical features of schizophrenia
Violence in schizophrenia is heterogeneous in its origin and
manifestations. It may be directly related to clinical symptoms. One hypothesis
links elevated rates of violence among people with mental illness to a small
set of delusional psychotic symptoms-so called threat/ control-override (TCO)
symptoms. These symptoms are elicited by questions like "dominated by
forces beyond you", "thoughts put into your head", and
"people who wished you harm". However, a large study suggested that although
delusions can precipitate violence in individual cases, they do not increase
the overall risk of violence (Appelbaum et
al.,2000). Delusional motivation of violence appears to be rare.
Command hallucinations to harm others may increase risk of violence,
although the level of compliance with such commands varies. In general,
positive symptoms of schizophrenia are associated with an increased risk of
violence, whereas negative symptoms show the opposite relationship (Swanson et al.,2006). Finally, there is
consistent evidence linking impaired insight to violence (Lera et al.,2012). This effect may be
indirect, mediated through the reduced adherence to treatment that is
associated with poor insight (Czobor et
al.,2013). Contrary to the belief of many clinicians, much of
the violence committed by schizophrenia patients does not seem so
be directly related to psychotic symptoms. Recent evidence suggests that
violence among adults with schizophrenia may follow at least two distinct
pathways-one associated with premorbid conditions, including antisocial
conduct, and another associated with the acute psychopathology of schizophrenia
(Swanson et al.,2008).
In that study, adherence with antipsychotic medications was
associated with significantly reduced violence only in the group without a
history of conduct problems. In the conduct problems group, violence remained
higher and did not significantly differ between patients who were adherent with
medications and those who were not (Swanson et
al.,2008). Since the outcome did not depend on whether these patients
actually did take the medication, we can infer that a history of conduct
disorder is associated with reduced effectiveness of antipsychotics.
This hypothesis remains to be tested. These findings are
consistent with previous observations indicating that only about 20% of
assaults on a psychiatric ward was directly attributable to psychotic symptoms
like delusions or hallucinations (Nolan et
al.,2003). The other assaults appeared to be due to confusion,
impulsiveness, or co-morbid antisocial personality disorder/psychopathic. Thus,
there are multiple pathways to violence in schizophrenia, and this etiological
heterogeneity has implications for treatment (Volavka & Citrome 2011).
Long-term Treatment
(Pharmacological treatment)
Atypical antipsychotics are the mainstay of the longterm treatment
of aggressive behavior in schizophrenia.
Clozapine is the gold standard for the treatment
of schizophrenia patients exhibiting violent behavior. Two randomized
controlled double-blind trials confirmed the antiaggressive effects of
clozapine. The first trial compared clozapine, olanzapine, risperidone, and
haloperidol in patients with schizophrenia or schizoaffective disorder.
Analyses of the hostility item of the PANSS have demonstrated superior efficacy
of clozapine in comparison with risperidone and haloperidol. Neither
risperidone nor olanzapine showed superiority to haloperidol. Additional
analyses of the same trial focused on incidents of overt physical aggression
instead of hostility The results demonstrated overall superiority in
antiaggressive efficacy of all three atypicals over haloperidol. (Volavka et al.,2004).
The second trial compared clozapine, olanzapine, and risperidone
in patients with schizophrenia or schizoaffective disorder who were selected
for being violent. Efficacy of clozapine to reduce incidents of overt physical
was superior to olanzapine, which was in turn superior to haloperidol.
Although its antiaggressive efficacy is firmly established, clozapine
is not a panacea (Volavka 2012). Many patients, perhaps as many as 50% , fail
to respond to this medication (Lieberman et
al.,1994). These non-responders could be the patients with a history of
conduct disorder as discussed above (Swanson et al., 2008).
Furthermore, clozapine does not exhibit its full antiaggressive
effect until an effective dose – around 500 mg/day – is reached (Volavka et al., 2004). Also, patients sometimes
refuse or discontinue clozapine for various reasons, including the need for
blood monitoring. Finally, some patients cannot receive or continue clozapine
treatment for medical contraindications or adverse effects. (Krakowski et al., 2006).
Olanzapine is effective against overt physical aggression
(Krakowski et al., 2006) and against
hostility (Volavka et al.,2002) in
long-term schizophrenia patients. Olanzapine’s antiaggressive effects were weaker
than those of clozapine (Krakowski et
al., 2006), and not distinguishable from other atypical antipsychotics
(Swanson et al.,2008). However, in
first episode schizophrenia, it was superior to haloperidol, quetiapine, and
amisulpride in its effect against hostility (Volavka et al., 2011).
Risperidone reduced violent behavior and hostility in
open studies of schizophrenia (Chengappa et
al., 2000). An analysis of a randomized doubleblind study of risperidone in
schizophrenia patients confirmed its superiority over placebo in reducing hostility.
Other comparisons of risperidone with various antipsychotics in randomized trials
showed mostly no significant differences in antiaggressive effects (Swanson et al., 2008).
Aripiprazole. Five randomized, double-blind studies of
patients with schizophrenia or schizoaffective disorder compared aripiprazole
with placebo. Three of the studies included haloperidol as a comparator.
Posthoc analyses showed that aripiprazole was superior to placebo and not
significantly different from haloperidol in reducing hostility (Volavka et al., 2005).
Quetiapine. Open studies supported effectiveness of quetiapine
against hostility and aggression Villari et
al., 2008). These observations were confirmed by post-hoc analyses of
randomized doubleblind trials demonstrating superiority of quetiapine over
placebo in reducing aggression in schizophrenia patients (Arango
& Bernardo 2005). In another study, quetiapine’s antiaggressive effects
were similar to other atypical antipsychotics, but they were weaker than those of
perphenazine (Swanson et al., 2008).
Ziprasidone. Post-hoc analyses of effects on hostility
used data from a randomized, open-label study comparing ziprasidone with
haloperidol in schizophrenia and schizoaffective disorder (Citrome et al. 2006).
Both drugs reduced hostility; ziprasidone was superior to haloperidol only
during the first week of the study. Ziprasidone’s anti-aggressive effects were
similar to other antipsychotics (Swanson et
al., 2008).
Other medications
Anticonvulsants and lithium are widely used for the
adjunctive treatment of aggressive behavior in schizophrenia patients. However,
this treatment is not supported by adequate empirical evidence. While it may be
effective in individual patients, such treatment must be closely monitored, and
it must be stopped if it fails to show clear benefits (Citrome 2009).
Adrenergic beta-blockers showed antiaggressive action in several
studies and case reports and this approach has been recommended for violence in
schizophrenia as a second-line treatment (Kane et al., 2003).
Beta-blockers reduce blood pressure and pulse rate; and these adverse
effects are partly responsible for the recent lack of interest in exploring
beta-blockers as a treatment of violence. Beta-blockers have been supplanted by
antipsychotics. Nevertheless, antipsychotics are not always effective; efficacy
of adjunctive betablockers
in the treatment of persistently aggressive schizophrenia patients
should be studied further.
Recently published meta-analyses indicating an association between
the polymorphism of the catecholo- methyl transferase (COMT) gene and violence
in schizophrenia may rekindle interest in this area (Singh et al.,2012).