BIPOLAR DISORDER | EPIDEMOLOGY | CLINICAL FEATURES | TREATMENT | PHARMACOLOGICAL MANAGEMENT



The prevalence of violent behavior in bipolar disorder is at least as high as in schizophrenia. Clinicians have been aware of the problems with violent behavior in bipolar disorder for a long time. However, research efforts in this area have lagged behind analogous work in schizophrenia (Latalova et al., 2009).


Epidemiology
A sample representing the population of the United States was collected for National Comorbidity Survey (NCS) between 1990 and 1992. Diagnoses (“lifetime” and “last year”) and history of aggressive behavior during the preceding year were determined by interviews. Aggressive behavior (or its proxy, “trouble with the police or the law”) was reported by 12.2% of individuals with the diagnosis of bipolar disorder, 8.2% with alcohol abuse, 10.9% with drug abuse and 1.9% with no disorder. (Watson et al., 2005).
All diagnoses mentioned above are lifetime. The analogous numbers for “last year” diagnoses were 16.0%, 9.1%, 19.8%, and 2.0%. Thus, when the patient was exhibiting symptoms of bipolar
disorder (or substance abuse) during the 12-month period covered by the aggression survey, the frequency of reported aggression increased. Thus, comorbidities increased the frequency of aggressive behavior. The NESARC study conducted in 2001-2002 involved interviews to assess lifetime prevalence of aggressive behavior as well as the lifetime DSM-IV psychiatric disorders in 43093 adults representing the population of the United States (Pulay et al. , 2008). The lifetime prevalence of aggressive behavior after age 15 was 0.66% in persons without lifetime psychiatric disorder, but 25.34% and 13.58% in bipolar disorder I and II, respectively. The respective odds ratios were 3.72 (2.94-4.70) and 1.77 (1.26-2.49). These numbers represent a mixture of pure bipolar disorders (without comorbid diagnoses) and bipolar disorders with comorbid diagnoses. The prevalence of aggressive behavior in pure bipolar (without comorbidity) was 2.52% and 5.12%, respectively. Comparable prevalence of aggressive behavior for pure alcohol dependence and drug dependence was, respectively, 7.22% and 11.32%.
The rates of comorbidity of bipolar disorder with alcohol dependence, drug dependence, paranoid personality disorder, and antisocial personality disorder were significantly elevated (Grant et al. 2005). These comorbidities increase the risk of violence. (Pulay et al., 2008).
Another set of analyses of the NESARC study sought to determine the prevalence of criminal justice involvement during episodes of mania and to identify whether specific manic symptoms contribute to this risk (Christopher et al. 2012). Analyses aimed to determine the rate of legal involvement (being arrested, held at the police station, or jailed) of individuals with bipolar I disorder during the most severe lifetime manic episode. Among the 1,044 respondents (2.5%) who met criteria for having experienced a manic episode, 13.0% reported legal involvement during the most severe manic episode. Legal involvement was more likely among those with symptoms of increased self-esteem or grandiosity, increased libido, excessive engagement in pleasurable activities with a high risk of painful consequences, having more manic symptoms, and having both social and occupational impairment (Christopher et al. 2012).
Data on diagnoses, sociodemographic information, and violent crime in Sweden from January 1, 1973, through December 31, 2004 were obtained for a study of bipolar disorder (Fazel et al. 2010b). Individuals with 2 or more discharge diagnoses of bipolar disorder (n=3743), general population controls (n=37 429), and unaffected full siblings of individuals with bipolar disorder (n=4059) were the subjects. After the first diagnosis, 355 individuals with bipolar disorder (9.5%) committed violent crime compared with 629 general population controls (1.7%) (adjusted odds ratio, 6.6; 95% confidence interval, 5.8-7.6). The risk was most increased in patients with substance abuse comorbidity (adjusted odds ratio, 19.9; 95% confidence interval, 14.7-26.9). However, there was still a significant risk increase even in patients without substance abuse comorbidity (adjusted odds ratio, 3.1; 95% confidence interval, 2.6-3.8) (Fazel et al. 2010a). Clinical observations during hospitalization and immediately prior to it suggest that the risk of violence is high during acute manic.
A study compared the prevalence of aggression in bipolar disorder patients with persons showing other psychopathology and healthy controls. Subjects with bipolar I and bipolar II disorder
(n=255), other psychopathology (n=85), and healthy controls (n=84) were recruited. Aggression was measured using a questionnaire. Bipolar disorder patients showed significantly higher aggression scores than the other groups. Independent of the severity of bipolar disorder and polarity of the episode, those in a current mood episode showed significantly higher aggression
scores than those not in a current mood episode. (Ballester et al., 2012)
Subjects with current psychosis showed significantly higher total aggression scores, hostility, and anger than those without current psychosis (Ballester et al., 2012).
Clinical features
A factor analysis showed that aggression in bipolar disorder was associated with paranoia and irritability. This irritable aggression remained stable in time across consecutive manic episodes.
In a more detailed study, aggression was associated with irritability, uncooperativeness, impatience, and lack of insight. Subsequent cluster analysis of this data set revealed four subtypes of mania, one of them labeled as “aggressive”. In a study of patients with bipolar disorder, manic or mixed, aggression appeared with similar frequency in the two subtypes.
Thus, aggression is a feature of manic and mixed episodes of bipolar disorder, develops in the context of irritability, and may be an enduring individual trait.
The preceding studies investigated symptoms occurring contemporaneously with aggression. We will now take a broader perspective, looking at concomitants of aggression in bipolar disorder that are not necessarily contemporaneous with aggressive behavior.
Psychological links between inward and outward aggression have been of interest to psychiatrist since Freud. Relation between suicide and aggression in bipolar disorder is particularly important. Patients with bipolar disorder who had a history of suicide attempt were compared with those without such a history (Oquendo et al., 2000).The attempters scored higher on scales assessing hostility and lifetime history of aggression.
In a similar study of bipolar patients, suicide attempters were compared with non-attempters. The attempters scored significantly higher on a hostility scale particularly on the subscale that assesses overt physical aggression. They also showed higher level of impulsiveness. Impulsiveness and hostility were correlated in the attempter subset.
A study compared impulsivity and aggression between 143 controls, 138 bipolar disorder and 186 major depressive disorder patients with or without a history of suicide attempt (Perroud et al. 2011). The patient groups showed higher impulsivity scores and more severe lifetime aggression than controls.
Impulsivity distinguished major depressive disorder subjects without a history of suicide attempt from those with such a history, but not in bipolar disorder subjects.
Impulsive and aggressive traits were strongly correlated in suicide attempters (independently of the diagnosis) but not in non-suicide attempters. Thus, impulsivity may be a suicide risk marker in major depressive disorder but not in bipolar disorder, and its strong correlation with aggressive traits seems specifically related to suicidal behaviors (Perroud et al. 2011) As noted in the epidemiological studies described above, comorbidity with other disorders elevates the risk of aggression in patients diagnosed with bipolar disorder, and the comorbidity rates are high. Clinical studies are consistent with the epidemiological ones. A study showed that alcohol abuse/dependence comorbidity ranged between 31.9% and 47.3%, drug abuse/ dependence abuse range was 15.1-34.2% , depending on age of onset (Perlis et al. 2004). Early onset was
associated with higher risk of comorbidity. Other studies yield a range of 17-64% for substance abuse comorbidity with bipolar disorder (Baldassano 2006).
The impact of alcohol abuse on symptom presentation was examined in patients with acute bipolar mania with and without current alcohol abuse (Salloum et al., 2002). The comorbid group showed higher levels of impulsivity and aggressive behavior. In general, the evidence for the role of substance use disorders in the pathophysiology of aggression in the mentally ill is overwhelming (Fazel et al., 2010).
Comorbidity of bipolar disorder with antisocial personality disorder was demonstrated in the NESARC sample as described above (Grant et al., 2005). It was also described in clinical vignettes and observations in forensic facilities and prisons (Good 1978). This comorbidity would of course elevate the risk of aggression since the diagnosis of antisocial personality disorder is partly defined by it.
The NESARC analysis does not give specific comorbidity rate of bipolar disorder with borderline personality disorder (Grant et al., 2005). However, that comorbidity does elevate the risk of aggressive behavior, as demonstrated by a study of bipolar patients (Garno et al., 2008). In that study, trait aggression was assessed by the Brown-Goodwin scale, and history of childhood trauma was ascertained by a questionnaire. Trait aggression was strongly related to the presence of comorbid borderline personality disorder as well as the history of childhood trauma and the severity of current manic and depressive symptoms (Garno et al., 2008).

Treatment and Management of aggression in bipolar disorder
Acute agitation is a common presentation of a manic episode. Staff training in behavioral management of acute agitation is extremely important, since their intervention may prevent an escalation of behavioral dyscontrol. The first interventions include clearing the room, having staff available to assist, and encouraging the patient to talk about his\her needs and concerns
(Volavka et al. 2012). Prompt use of sedating or calming agents is important.
Benzodiazepines: Benzodiazepines are commonly used, particularly where alcohol or sedative withdrawal is a possibility.
Lorazepam is a benzodiazepine that is reliably absorbed intramuscularly, has no active metabolites and has a half-life between 10 and 20 hours; usual dose is 0.5–2.0mg every 1–6 hours. Caution is required when respiratory depression is a possibility. Lorazepam is not recommended for long-term daily use because of the potential for tolerance and dependence.
Pharmacological management
Irritability and aggression comprise a core feature of mania, and successful treatment of the underlying manic episode is therefore expected to reduce or eliminate the concurrent aggressive behavior. Thus, long-term antiaggressive pharmacological treatment of manic patients is co-extensive with the general management of bipolar disorder. Such general information is outside of the scope of this review. The reader is referred to generally available guidelines (Collins et al. 2010).
Non-pharmacological management
Cognitive-behavioral therapy (CBT) has been used to address many aspects of bipolar disorder that raise the risk of aggression, including comorbid personality disorders and substance use disorders as well as treatment nonadherence. A randomized controlled study of CBT in bipolar patients focused on treatment adherence. In comparison with a control group, the patients who received six CBT sessions demonstrated superior adherence to medication, better understanding of their treatment, and fewer hospitallizations. Manuals for the use of CBT in bipolar disorder are available (Basco & Rush 2007). Parts of the manuals are specifically directed towards treatment adherence and substance use problems.
Family members are among the most frequent victims of assaults by patients diagnosed with mental disorders. Family-focus psychoeducational treatment addresses problems in communications in the family, lack of information about the illness, and lack of skills in conflict resolution (Herman et al. 2004).
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