Violent
Behavior in Youths with Bipolar and Related Disorders:
Evaluation and Treatment
By Arline Kaplan © 2000 (All Rights Reserved)
Bipolar disorder and related problems are "clearly over represented"
among delinquent and incarcerated youth, said Hans Steiner, M.D., director of
training for the Division of Child Psychiatry at Stanford University School
of Medicine in California.
Steiner spoke on violent behavior in adolescents with bipolar disorder at the
American Psychiatric Association’s 153rd annual meeting in Chicago.
The prevalence of bipolarity in incarcerated juvenile populations has been under
studied, according to Steiner, who is also professor of psychiatry and behavioral
sciences at Stanford. To date, there is a study by Frederick A. Marsteller,
Ph.D., and colleagues at Emory University School of Medicine; a study from South
Carolina with a much smaller number and an ongoing study by Steiner and colleagues.
Marsteller and colleagues (unpublished data) assessed the prevalence of psychiatric
diagnoses in juvenile offenders in Georgia using a Diagnostic Interview Schedule
for Children, Version 2 (DISC-2), based on the Diagnostic and Statistical
Manual of Mental Disorders, Third Edition, Revised (DSM-III-R).
The rates of bipolarity were 2.2% in white males, 4.4% in black males, 6.3%
in white females, and 3.1% in black females. Overall, the rates were 3.8% (95%CI,
2.3% to 5.3%).
Currently, Steiner and his colleagues are conducting a study of 1,000 juvenile
offenders housed in the California Youth Authority (CYA). Funded by National
Institute of Justice grant, the study’s purpose is to estimate the prevalence
of mental health problems in the CYA population, evaluate assessment tools,
and examine the relationship among mental health problems, prior criminal behavior,
and personality characteristics and functioning within institutional environments.
Steiner shared some preliminary results of the study.
"We looked at the first 300 [juvenile offenders], so what I will show …must
be taken with a grain of salt. But still what you will see is that bipolar disorders
are clearly over represented in this population," he said.
Using
the Structured Clinical Interview for DSM-IV (SCID), the investigators found
that 2% of the incarcerated juveniles have bipolar 1 disorder, 4% have bipolar
II and 7% have cyclothymia (Steiner, 1999; Steiner and Wilson., 1999; Steiner
et al., 1997 ). For comparison, the incidence of bipolar disorders in the general
adolescent population is about 1% (Carlson and Kashani, 1988; Lewinsohn et al.,
1995, as cited in Chang et al., 2000).
In a 1999 study, Steiner and colleagues looked at the clinicians’ diagnoses
on the charts of clinically referred incarcerated youth.
"What we found is that about 12% of 383 clinically referred males, and
20% of 90 females fulfilled criteria of some form of bipolar disorder, and the
most predominant form was cyclothymia," he said. "So clearly these
rates are elevated, although it is also quite clear that they will not explain
most of violent delinquent behavior. There are other factors."
"Tremendously high comorbidity" exists between attention-deficit/hyperactivity
disorder [ADHD] and bipolar incipient types of behavior, conduct disorder [CD],
oppositional defiant disorder [ODD], anxiety disorder, major affective disorder,
and later on, substance use disorder and somatization disorder, Steiner said.
Prepubertal bipolar disorder may present with sustained conduct and impulse-control
problems (Chang et al., 2000).
Steiner cited a study he completed with Kiki Chang, M.D., and Terence Ketter,
M.D., that look at psychopathology among 60 children ranging in age from 6 to
18 years old who had at least one biological parent with bipolar I or II disorder
(Chang et al., 2000). They found that 28% of the sample had ADHD, compared to
a 3% to 5% prevalence in school-age children generally. Additionally, 15% had
major depressive disorder or dysthymia, 15% had bipolar disorder or cyclothymia,
10% had ODD, 3% had obsessive-compulsive disorder, 3% had tic disorder and 5%
had other anxiety disorders. Eighty eight percent of the children with bipolar
disorder had comorbid ADHD, and both bipolar disorder and ADHD were more likely
to be diagnosed in males.
"What we got from this study of children of extremely high risk is essentially
the same kind of overlap and comorbidity that has been described before,"
Steiner said.
Because of the overlap between disruptive behavior disorders and bipolar disorder,
Steiner devoted much of his presentation to a discussion of aggression and the
pharmacological treatment of aggression in juveniles. He approached the topic
from a developmental perspective that presumes some adaptive value in aggression,
properly socialized and channeled.
Aggression is defined in Webster’s Dictionary, Steiner said, as
"the practice or habit of being aggressive (i.e. starting attacks, being
hostile, pushy, bold, full of initiative," containing both a very negative
and positive pole of connotation.
"The idea is not that aggression is always pathological and bad and needs
to be eradicated, the idea is that aggression is part of a signal system that
gets you to conduct your life in useful and adaptive ways." Steiner said.
"So if the heart of your treatment plan is eradication of aggression, I
don’t think that is a particularly useful concept."
Other related concepts Steiner defined were violence: a use of force aiming
at physical injury; anger: "the emotion that fuels this whole system and
gets it going," serving as a trigger for aggressive and violent acts; and
impulse control: a subsystem of personality trait of restraint that "channels
and guides anger, aggression and violence."
"The [aggression] system can be influenced by pure coincidental environmental
factors, constitutional factors, active socialization, and then most relevant
to us, environmental trauma, psychiatric trauma and psychiatric illness, such
as bipolar disorder," he said.
There are multiple ways of subtyping aggression, according to Steiner.
o By target (e.g., territorial, sexual, homicidal)
o By channel of expression (e.g., verbal, behavioral)
o By pattern (e.g., escalating versus intermittent)
o By motive and anticipated outcome (e.g., predatory, defensive) or
o By some trait associations (e.g., underrestrained, overrestrained).
The literature on aggression subtypes is "fairly voluminous," Steiner
said. One distinction that he believes has held up well in the literature is
that of reactive versus proactive aggression (Dodge et al., 1997), mirrored
somewhat by the affective versus predatory distinctions of Vitiello and Stoff
(1997) from the National Institute of Mental Health.
"In predatory or proactive aggression, what you have is a careful mapping
out of what it is that you are going to do. If you are aroused, it is not very
much…From a motivational point of view, you anticipate that something good
will happen as a function of your aggressive act," he said.
In contrast, the reactive, affective or defensive act usually arises in reaction
to a negative emotion, according to Steiner.
"Something bad has happened, you now become upset, and you become aggressive
in order to avert a negative outcome," he said.
In the delinquent population and conduct disorder populations, the affective/defensive/reactive
kinds of aggressive acts are much more common than the predatory acts, Steiner
added.
As they have worked with the juvenile delinquent population at the California
Youth Authority, Steiner and his colleagues have further divided the reactive,
affective, defensive violence subtype into escalating versus intermittent violence
(Steiner, 1997). Characteristics of escalating violence include increasing affect
leading to increasing aggression and diverse precipitants, such as trauma, frustration.
Characteristics of intermittent violence include affect which is tightly controlled
for long periods, homogenous precipitants specific to the person and the involvement
of significant others.
Steiner also briefly discussed Hans Eysenck’s theory of impulsivity which
links aggressive acts and impulsivity to low cortical arousal related to poor
functioning of the reticular activating system (RAS). Eysenck’s theory
"makes plausible why stimulants are sometimes quite effective in averting
antisocial acts," since stimulants improve RAS functioning, he said.
Another link described by Steiner was that of serotonin and aggressivity. That
line of investigation was actually started by Frederick Goodwin, M.D., research
professor of psychiatry at George Washington University, who in the 1970s discussed
the connection between serotonin and aggressivity, Steiner said.
"Several people have followed up on his leads, and essentially have shown
that serotonin not only leads to mood dysregulation problems but also to increased
impulsivity and heightened aggression [Apter et al., 1990; Coccaro and Kavoussi,
1997]," he said. "You also have problems with aggression if you are
lacking in tryptophan which is a precursor of 5-hydroxytroptophane, which is
the precursor of 5-hydroxytryptamine (Maas et al., 1993). Serotonin [dysfunction],
in particular, is associated with impulsive (i.e., reactive/affectively-charged
aggression) but not with predatory aggression (Linnoila et al., 1983)."
Typology in Clinical Cases
Having
summarized his research-based typology of aggression, Steiner then discussed
how to apply it to clinical cases and select appropriate treatment.
"When somebody comes to you and says ‘This particular kid is at risk,’
what do you do?" Steiner asked. He recommended first subtyping the youth’s
aggressive behavior into one of three categories: predatory; affective/reactive/defensive;
or situational.
"Situational acts are driven by peer influences," Steiner said. "Hanging
out with gang-affiliated friends will almost by necessity get you involved in
aggressive acts that are neither predatory nor affective/defensive….Needless
to say, those kinds of acts are not particularly amenable by psychopharmacology
but would be better addressed by peer intervention strategies, such as those
mapped out by the Oregon Social Learning Center [OSLC]. People there have shown
essentially if you deprive delinquent antisocial adolescents of a peer group
that is sort of admiringly, encouraging antisocial acts, antisocial acts of
[this type] decrease rather dramatically in frequency." (Located in Eugene,
Oregon, OSLC is a nonprofit, independent research center. It also receives National
Institute of Mental Health funding as a Prevention Research Center for conduct
disorders.)
Predatory aggression essentially consists "of premeditated acts of attack,
aggression and violence, and those acts cluster usually in kids with conduct
disorder without any particular comorbidity," Steiner said. "Later
on, of course, they cluster in antisocial personality disorders."
The vast majority of aggressive acts, Steiner said, are affectively driven.
"Now then you have to differentiate two other things. You have to look
at a pattern with which these aggressive acts unfold, and decide whether you
have a gradually escalating path or an intermittently explosive path. And there
is some evidence that two different acts will probably respond to different
forms of intervention," Steiner said. "What they both have in common
is that a negative outcome is anticipated, driven by negative emotion, and aggression
is used as a means to avert a negative outcome. In the escalating variety, kids
will describe the fact that they are in a bad mood, in response to a frustration,
and about anything that happens after that serves to essentially to put them
into a worse mood and makes it more and more likely that ultimately they will
become aggressive in some form or another."
In contrast, there is another subgroup of kids who in response to negative emotions
will hold onto their anger and aggression for considerable periods of time,
sometimes weeks and even months and then explosively discharge, Steiner explained.
This was the pattern that Steiner and colleagues found most commonly in youths
that have a combination of conduct problems and mood dysregulation.
A variety of treatment modalities are used in the management of aggression,
depending upon the child’s age and circumstances. With regard to the management
of aggression in young children, Steiner said "the best evidence we have
now is that early on, [the clinician] really needs to concentrate on the home
and the parenting."
Once the child enters school, manualized treatments can help the clinician intervene
on school sites with peers in school and school groups. Steiner recommended
using materials from Oregon’s Social Learning Center.
"Then in adolescence, you are adding a much more intensified peer intervention,"
Steiner said. He recommended that some form of psychotherapy be incorporated
into the treatment plan at all times.
"All of these techniques—behavioral, cognitive, psychoeducational,
explorative, psychodynamic, interpersonal—have some utility, he said, adding
that clinicians would find an excellent summary by Kazdin and Wassell (2000).
Psychopharmacological treatment of aggression in children and adolescents involves
several classes of drugs: antipsychotics (dopamine [DA] blockade); anticonvulsants
(gamma aminobutyric acid [GABA] agonism); mood modulators (serotonin [5-HT]
increase), sedatives (sedation), anxiolytics and beta-blockers (reduction in
noradrenergic [NA] activity), stimulants (increase in RAS system), Steiner said.
However, the list gets drastically curtailed when limited to controlled clinical
trials of medications for the treatment of conduct disorder, he said. In randomized,
placebo-controlled trials, a total of 483 subjects were involved, predominately
male (Campbell et al., 1984; Campbell et al., 1995; Findling et al., 1999; Klein,
1991; Klein et al., 1997; Malone et al., 1998; Rifkin et al., 1997; Sheard et
al., 1976; Silva et al., 1991; Steiner et al., 1999). Most of the subjects were
in a controlled, structured setting.
"All of these trials are of very short duration, ranging from one to three
months…We have studied about six agents: lithium [Eskalith, Lithobid],
divalproex [Depakote], carbamazepine [Tegretol], haloperidol [Haldol], methylphenidate
[Ritalin] and risperidone [Risperdal]," he said. "One of the problems
of this literature is that everybody uses different outcome measures. There
is no appropriate, developmentally sensitive norm or standardized measure of
aggression than spans from ages 5 to 18."
"Of these studies, seven showed a drug effect over placebo …of the
studies that showed an effect, most of them used mood stabilizers—lithium,
carbamazepine, or as in our case, divalproex sodium," Steiner added.
In their own research, Steiner and colleagues sought to evaluate the effectiveness
of the divalproex in preventing angry and aggressive outbursts and other uncontrollable
emotions among 61 violent, conduct disordered youths, aged 14 to 18.
"These are convicted, aggressive kids who have committed murder, manslaughter,
etc. We had to screen about 205 to get these 61," he said. Of the 61, 58
completed all necessary outcome measures and were retained in the final analyses
The youths were randomized into two groups, one that received low-doses of divalproex
(up to 250 mg/day in divided doses) and the other, high doses (usually about
1000 mg/day in divided doses).
"It took about two weeks to get the kids into therapeutic range. They were
then managed by the clinical team, and there was a research team that blindly
assessed their progress and outcome," he said. "The primary recruitment
target was conduct problems."
Youths with comorbid bipolar disorder or schizophrenia were excluded from the
study, but "we had the usual culprits in terms of comorbidity," he
said. All the youths were diagnosed with conduct disorder, but 88.5% also had
comorbid substance abuse disorder; 61%, some learning disability; 54%, some
affective disorder, primarily dysthymia; 51%, ADHD; and 21.3%, posttraumatic
stress disorder.
At the end of the seven-week trial, those in the high-dose group, had a much
more positive response than those in the low-dose group. The overall response
rate was in the low 30s, "which sort of maps onto the comorbidity with
mood and affect problems," Steiner said. (Kowatch et al. [2000] found
response rates to lithium and carbamazepine in children and adolescents to be
38%. In their study, the overall response rate was less than the response rate
in bipolar adolescents treated with divalproex—Ed.)
Steiner and his team also sought to determine which variables were affected
by divalproex. On a weekly basis, the investigators measured impulsivity and
negative affect. Both conditions improved.
"The differential effect came in the impulsivity factor. The effect size
was fairly good, it was .76, which is respectable. The group that was in high-dose
condition…essentially showed an increase of impulse control as the kids
got treated," he said. "Parenthetically, I can tell you that a lot
of the kids had a lot of trouble after they stopped being on the medicine."
Other Studies
Subsequent
to Steiner’s presentation at APA, two other controlled studies were published
looking at pharmacological approaches for treatment of disruptive behaviors
in youths.
Malone et al. (2000) conducted a controlled trial of lithium in hospitalized
children and adolescents with conduct disorder that had histories of severe
aggression. Forty young people were randomized to treatment, and all completed
the study; 20 received lithium, and 20 received placebo. Sixteen of the 20 subjects
in the lithium group were rated as responders on the Global Clinical Judgements
(Consensus) Scale, compared to six of 20 in the placebo group. Ratings on the
Overt Aggression Scale decreased significantly for the lithium group versus
placebo group (P=.04). More than half of the subjects in the lithium group experienced
nausea, vomiting and urinary frequency.
A randomized, double-blind, placebo-controlled trial conducted by Donovan and
colleagues (2000), found divalproex to be effective in treating explosive temper
and mood lability in children and adolescents who were being treated as outpatients.
Twenty children and adolescents (ages 10 to 18) who were diagnosed with either
conduct disorder or oppositional defiant disorder and who also had explosive
tempers and mood lability entered the study. The study had a two-phase, double-blind
crossover design with patients randomly assigned to phase I with divalproex
treatment for six weeks, immediately followed by phase II with placebo for six
weeks or vice versa. In phase I, eight of the 10 youths receiving divalproex
responded, whereas none of those receiving placebo did. In phase II, six of
eight medication responders in phase I received placebo and began relapsing.
Six of seven youths that had not responded to placebo in phase I did respond
to divalproex during phase II. (Response was defined by an independent evaluator
as a substantial [>70%] reduction from baseline in scores on both the Modified
Overt Aggression Scale and the SCL-90 anger-hostility items—Ed.)
"This preliminary study," Donovan et al. said, "replicates open-label
findings showing that divalproex is an efficacious treatment for explosive temper
and mood lability in disruptive children and adolescents."
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(AK102)
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