08-09-1362-carlson.fm

Treatment in Psychiatry
Treatment in Psychiatry begins with a hypothetical case illustrating a problem in current clinical practice. The authorsreview current data on prevalence, diagnosis, pathophysiology, and treatment. The article concludes with the authors'treatment recommendations for cases like the one presented. Treating the Childhood Bipolar Controversy:
A Tale of Two Children
Gabrielle A. Carlson, M.D.
low frustration tolerance. He too was severely hyperac-
tive and impulsive, and he had fine motor problems. Be-
cause he was close to grade level, his school was un-
w il l i n g to p rov id e s e r vi c es . He h a d ta k en m i xed
amphetamine salts from ages 5 to 9; this medication was
hildren for whom the differential diagnosis includes stopped when his aggressive outbursts intensified and a
bipolar disorder and/or attention deficit hyperactivity dis- diagnosis of bipolar disorder was made. He was then
order (ADHD; combined type) are usually complex and treated with a series of atypical antipsychotics and anti-
present thorny assessment and treatment problems. The convulsants, together and separately, but his behavior
cases of “Seth” and “Eric” illustrate these issues. They are and performance deteriorated so badly that he could
not be maintained in school. Eric’s outbursts occurred
presented in tandem to illustrate how information might when he was asked to work in school or do homework,
unfold and how the flow of information directs treatment when he wanted something that his teachers or parents
in situations where the question of bipolar disorder and/ would not give him, and during transitions from subject
to subject in class or when asked to go anywhere without
being given a great deal of warning.
Background Information on Seth
Other than being very fidgety and easily distracted and
repeatedly asking when the interview would end, Eric’s
Seth, age 10, was referred by his school principal for
mental status was normal.
his impulsive behavior (e.g., pulling fire alarms), aggres-
Eric’s daily medication regimen consisted of 750 mg of
sive behavior (e.g., pushing everything off the principal’s
divalproex and 400 mg of quetiapine.
desk and trying to tip it over when brought to his office),
Eric’s maternal grandmother had bipolar I disorder,
and frequent outbursts. His outbursts consisted variously
which was treated successfully with ECT. His father had a
of cursing and screaming, hitting others and himself, and
childhood history of ADHD and had been in recovery
throwing objects. They occurred several times a week
from alcohol and cocaine abuse for 10 years.
when he felt thwarted, insulted, or provoked. His mother
was frightened for the safety of Seth’s younger sisters.
The Clinical Problem
When seen for emergency consultation, Seth appeared
agitated and had rapid, pressured, off-topic speech. He
Seth and Eric highlight the “bipolar disorder versus claimed that he did not remember what happened in
ADHD” or “bipolar disorder and ADHD” controversy in the principal’s office.
preadolescent children. They both had symptoms of Intake information revealed that Seth had been a
ADHD, but they also had symptoms of severe mood labil- mildly language delayed, hyperactive, dangerously im-
pulsive toddler who could not sleep at night. By age 4,
ity, inadequate response to ADHD treatment (or any other he had experienced many moves and observed domes-
medication for that matter), and family histories of mood tic violence. In his Head Start program, he began to
disorders. Youngstrom et al. (1) attribute some of the bipo- throw “megawatt fits.” Methylphenidate made his be-
lar/ADHD controversy to researchers’ use of different con- havior worse, and by age 5 a diagnosis of bipolar disor-
ceptualizations of bipolar disorder, different diagnostic in- der was made because of his rages. Subsequently, he
terviews, and different criteria to define study samples.
was treated unsuccessfully with risperidone, aripipra-
They also note that researchers’ definitions may alter the zole (which caused a 40 lb weight gain), divalproex, ox-
DSM-IV criteria and do not necessarily reflect how the di- carbazepine, and topiramate, ultimately arriving at his
current regimen, which consisted of 25 mg of atomoxe-
agnosis is used in clinical practice.
tine, 0.1 mg of clonidine, and 25 mg of lamotrigine, all
The question of the prevalence, pathophysiology, and administered nightly.
treatment of bipolar disorder in children (versus adoles- Seth’s mother had experienced a postpartum depres-
cents) will obviously depend on how one diagnoses it. Liter- sion. His father had numerous learning disabilities and a
ature review is unhelpful since most authors combine child substance abuse problem. They were divorced.
and adolescent data or data on bipolar I disorder, bipolar IIdisorder, and bipolar disorder not otherwise specified.
Background Information on Eric
Whether research groups have used more liberal or more Eric was also age 10. Consultation was sought because
conservative definitions of episodes, euphoria, and grandi- of his unpredictable, explosive behavior and extremely
osity, they can marshal data to validate their approach.
This article is featured in this month’s AJP Audio.
Am J Psychiatry 166:1, January 2009 TREATMENT IN PSYCHIATRY
Besides the question of how broadly or narrowly to de- that has been conducted on acute mania in children and fine mania in youths, there is the related question of how adolescents with lithium was negative (13).
to diagnose children with explosive, aggressive behavior.
Treatment for ADHD includes stimulant medications or Previously these symptoms in children were included atomoxetine, behavior modification, and academic ac- within the broad definition of hyperkinesis, the predeces- commodations if needed (14); data also suggest that in sor of ADHD. Laufer and Denhoff (2) described “behavior cases where ADHD is accompanied by extreme aggression of almost volcanic intensity” and changeability such that in the absence of a mood disorder, stimulants are some- the child could be “sometimes good and sometimes bad.” what beneficial (15–17). There is, in fact, a mandate to be- In DSM-III, this emotion component of hyperkinesis was gin controlled studies of children whose aggression is not split off from the “core” attention and hyperactivity symp- satisfactorily addressed by ADHD treatments alone (3).
toms, and the explosive, aggressive behaviors were There have been three small but systematic studies indi- absorbed into the “associated symptoms” of ADHD, oppo- cating that the addition of ADHD medications to anti- sitional disorder/oppositional defiant disorder, and con- manic medications in children with bipolar disorder and terms—“affective,” “impulsive,” or mind, and to continue to do not cause children to develop bipo- lar disorder (21–23), and where there is the presence of prominent and chronic (at least 1 year) an- moxetine-induced mania in children with ADHD, but to ger/irritability or sadness, with severe tantrums occurring date, placebo-controlled trials of children with ADHD and several times a week in multiple settings. Other symptoms depression have not provided evidence of a placebo-drug that may be seen in both mania and ADHD—insomnia, difference (27). The phenomenon of switching and drug- distractibility, flight of ideas, pressured speech, and intru- induced disinhibition is difficult to study (28), and non- siveness—are also present. More than 80% of these chil- stimulant treatment of ADHD needs such attention.
dren have comorbid ADHD and oppositional defiant dis- Finally, evidence suggests that atypical antipsychotics, lithium, stimulants, and valproate are effective for treating Although debate rages about whether severe ADHD aggression (29). The ADHD practice parameter thus recom- symptoms, fluctuating behavior, and short temper with mends the addition of these medications to ADHD treat- significant aggression represent a virulent form of ADHD ments for patients who have ADHD plus aggression (14).
or a juvenile subtype of bipolar disorder, there is an evi-dence base, albeit a small one, for treating both conceptu- Applied Assessment and Treatment
alizations—that is, mania with or without ADHD as well asADHD with explosive aggression. Thus, practice parame- Diagnosis Expectations
ters (6) and consensus documents (7) suggest that in bipo- Until we truly understand early-onset bipolar disorder, lar disorder mood and/or mania should be treated first, it will be important to acknowledge the different view- and if ADHD symptoms remain, they should be addressed points about the condition and to determine both what with evidence-based treatments for ADHD. Most of the parents’ understanding is and why they want to know data for effective treatments for mania in children (down whether the diagnosis pertains to their child. For instance, to age 10) and adolescents come from FDA-requested, in- Seth’s mother had been told that his rages had prompted dustry-sponsored studies of medications approved for the bipolar disorder diagnosis. She had not described mania in adults. Data have been published or presented manic episodes—that is, distinct periods when Seth’s demonstrating that for acute or mixed mania, about 50% mood was clearly different from usual, lasting at least sev- of the patients treated with olanzapine, risperidone, que- eral days with concurrent elation/irritability, grandiosity, tiapine, or aripiprazole improve about 50%, compared and accelerated verbal and physical activity. Rather, she with a response of about 25% with placebo (8, 9). Results noted that he became incredibly enraged for up to an hour for divalproex are mixed (10, 11), and results for other when he did not get his way, was disappointed, or felt in- mood stabilizers (e.g., oxcarbazepine) are disappointingly sulted. Some investigators (30) would concur that this pre- negative (12). A large-scale placebo-controlled study of sentation is likely bipolar disorder; others (4) would not lithium is under way, but at this time the only similar study diagnose bipolar disorder in the absence of discrete manic Am J Psychiatry 166:1, January 2009 TREATMENT IN PSYCHIATRY
episodes. Seth’s mother wanted to know if he really had bi- ously at grade level, experienced a drop in grades over the polar disorder in order to “find the right medication.” past several years. It will be important to try to under- Eric’s bipolar disorder diagnosis was made by his refer- ring clinician after the apparent worsening of his symp- Parent and Child Interview
toms on stimulant medication, and it was additionallysupported by his positive family history. Unlike with Seth, Although interviews developed for the study of mood in Eric’s case there appeared to be a distinct period, after disorders in children have good reliability, what is rarely he began treatment with a stimulant, in which his mood discussed is the fact that reporting on one’s own behavior was markedly worse than usual, although it was not clear may pose a difficult cognitive task, and both parent and whether this period met other DSM-IV criteria for a manic child reports can be profoundly influenced by question episode. Regardless, some investigators view increased ir- ritability on stimulants and other medications as evidenceof a manic switch, which is especially portentous in the Seth’s Mood Disorder History and Mental Status
context of a family history of bipolar disorder (31). Unlike Even after careful questioning, Seth’s mother did not
Seth’s mother, Eric’s parents wanted to know their son’s make a case for episodes (distinct periods of markedly
trajectory. Current treatment was also important, but the different mood than usual) of mania or depression. On
long-term implications concerned them more.
the other hand, she was so overwhelmed and immobi-
lized by Seth’s behavior, and so desperately wanted him
Comprehensive Assessment
out of the house, that Seth’s psychiatrist did not feel that
Comprehensive, standardized parent and teacher rating her information was diagnostically reliable.
scales are an important preliminary part of an ADHD eval- Nor was Seth able to shed light on his “mood swings,”
uation (14). Screening measures have likewise been since he denied or forgot them. He did appear agitated
advocated for bipolar disorder (6). The best screens cover during the interview. His language impairment was obvi-
ous but could have reflected manic flight of ideas or (re-
the important comorbidities and “rule-outs,” including call that Seth was also language delayed) the chronic
ADHD, oppositional defiant disorder, conduct disorder, problems with pragmatic language seen in some chil-
anxiety and depressive disorders, psychosis, tic disorders, dren with ADHD (35). His cognitive difficulties may have
autism, and, of course, mania. These measures do not precluded his being able to truly understand the intent
make a diagnosis but, accurately completed, alert the cli- of questions about mania or depression. Note that the
nician to important problem areas to be pursued further.
mental status examination is more than a cross-exami-
Seth’s ratings showed parent and teacher concordance nation of the child about symptoms; it is an opportunity
to observe his mood, relatedness, language, and think-
for high levels of hyperactivity, impulsivity and distracti- ing ability.
bility, oppositional defiance, conduct disorder, general- For safety and diagnostic reasons, Seth was hospital-
ized anxiety, and deviant language items (rapid, excessive, ized and taken off medication while further information
off-topic speech). There were differences in mania ratings and observations were obtained. The working hypothe-
on the Child Mania Rating Scale (32), however. A parent sis was that he had ADHD, oppositional defiant disorder,
score of 16 was made up of items reflecting irritability, ex- and severe mood dysregulation (based on the frequency
plosive behavior, distractibility, and rapid speech. (Often it and severity of his explosiveness, the presence of other
is helpful to know not only a score but what items were ADHD symptoms, and the absence of clear episodes), al-
rated to achieve the score.) The teacher score was 24, re- though bipolar disorder had not been ruled out.
flecting, in addition to irritability and explosiveness, peri- Eric’s Mood Disorder History and Mental Status
ods when Seth was “wound up and excited” or had higherthan usual energy. Like Jensen et al. (33), we find that the Although Eric’s parents had endorsed many manic
reasons ratings are discordant, in this case between parent symptoms on rating scales, they had not really under-
and teacher, are as informative as specific scores. For in- stood the intent of the questions. The example given for
stance, Seth was explosive both at home and at school, but elated mood was how excited Eric got when his parents
his teacher noted additional symptoms. We need to know ca pitulated to his relen tless demands. Indeed, it
why there is a discrepancy between his mother’s and his sounded like he got more excited than the situation war-
ranted, but the thrill was short-lived. They agreed that
he was often silly, but the silly behavior was clearly at-
Seth’s school report underscored a notable disability in tention-seeking, not motivated by feeling wonderful or
math and written expression, which had been present euphoric. This behavior had caused peers to think of
since first grade. He had a full-scale IQ of 84, with espe- him as “immature,” and indeed, his silly behavior
cially poor performance in working memory and process- tended to be annoying, rather than infectiously funny, as
one often sees in hypomanic or manic children or adults.
Eric did became explosive when told “no,” but that had
Eric’s ratings evidenced different inconsistencies be- been a lifelong response. As he had gotten physically big-
tween parents and teachers. His parents noted manic and ger, the damage he inflicted was also greater. His parents
depressive symptoms in addition to severe ADHD and also thought his wish to continue playing instead of go-
oppositional defiant behavior, whereas his teachers en- ing to bed was evidence of decreased need for sleep. In
dorsed only ADHD and oppositional defiance. Eric, previ- this case, not only was the problem chronic but when he
Am J Psychiatry 166:1, January 2009 TREATMENT IN PSYCHIATRY
did manage to wangle a later bedtime, he was tired and
wild crush, and he began writing hundreds of incoherent
even more grumpy the next day.
poems to her. When the attending psychiatrist showed an
A careful medication history revealed that Eric’s stimu-
interest in the poems, Seth redoubled his efforts. His
lant appeared to have become less effective by the time
rapid speech increased, and he responded to interrup-
he was in third grade. Increased academic demands ex-
tions with anger. His weekly nurse-rated Child Mania Rat-
acerbated his frustration and led to outbursts in school
ing Scale score was 38, made up of observations indicat-
and at home. Stimulant-induced hypomania had proba-
ing increased irritability and energy (despite decreased
bly not occurred. When Eric’s referring psychiatrist
sleep), elevated mood, rapid and pressured speech, gran-
changed Eric’s diagnosis to bipolar disorder, stimulants
diosity, and erotic and hypersexual behavior.
were replaced with other medications, as recommended
Several explanations of Seth’s behavior were enter-
in guidelines for bipolar disorder (6), but Eric’s behavior
tained, including the possibility that his previous im-
deteriorated further.
provement had simply been a “honeymoon” (37), that
Eric candidly said that he knew if he persisted long
the mixed amphetamine salts had induced mania, or
enough in nagging his parents, they would relent. If that
that he was spontaneously experiencing a manic epi-
did not work, he would become enraged. While he felt
sode. A call to Seth’s outside teacher confirmed that she
bad for the trouble he caused, he felt entitled to what he
had observed similar episodes prior to the start of stimu-
wanted. This entitlement had been called grandiose by
lant medication. Seth’s mother agreed and was now able
his parents. He was very distressed in school because he
to distinguish mania from symptoms of ADHD plus oppo-
could not pay attention, was constantly in trouble, was
sitional defiant disorder. Thus, the rating scale differ-
rejected by peers, and hated anything to do with written
ences were now explained.
work, such as homework, since he could barely print, let
Neither increasing the dosage of Seth’s stimulant med-
alone write. He described himself as more happy than
ication nor stopping the medication altered his behavior.
sad, but he often felt discouraged. He did not meet crite-
He was impervious to the behavior management plan.
ria for major depression or dysthymic disorder.
Given a persistently elevated mood over a 1-week pe-
The hypothesis was raised with Eric’s parents that his
riod, in tandem with increased energy and signs of hy-
worsening behavior in third grade may have resulted
persexuality, Seth was considered to be exhibiting a DSM-
from frustration stemming from the increased demand
IV manic episode. Lithium was started both because it
for written work, homework, and more mature social
had never been tried and because his mother did not
skills. In addition, he had developed what has been
want him to take an atypical antipsychotic again. His be-
called a “coercive relationship” with his parents (36).
havior continued for several weeks and clearly consti-
That is, his behavior was so toxic that his parents gave in,
tuted an episode different from his “usual” self—which,
rewarding his outbursts and teaching him that aggres-
we had seen, was already compromised by his ADHD, op-
sive behavior was how to get what he wanted. His grand-
positional behavior, and difficult home situation.
mother’s history of bipolar I disorder had raised the
On lithium, Seth’s behavior eventually improved, but
specter of bipolar disorder, which was one reason his
not enough for his mother to manage. Since the alterna-
stimulant medication was stopped; yet his behavior and
tive was residential placement, his mother agreed to the
academic performance deteriorated further, and none
addition of risperidone (0.5 mg twice a day). On risperi-
of the bipolar treatments had helped. Bipolar disorder
done, Seth’s irritability diminished further. Mixed am-
could not unequivocally be ruled out, but Eric’s history
phetamine salts were started again, which improved his
suggested a diagnosis other than mania.
concentration; repeat IQ testing revealed a 16-point in-
crease, mostly due to improvements in working memory
Treatment and Discussion
and processing speed.
Seth was discharged to a combined behavioral pro-
Seth’s Treatment and Follow-Up
gram and a special education setting, on a regimen of
1200 mg of lithium daily, 0.5 mg of risperidone twice a
Seth was admitted to the hospital, his medications
day, and 15 mg of mixed amphetamine salts twice a day.
were discontinued, and he was observed with standard-
His discharge diagnoses were bipolar disorder, most re-
ized ratings for a week. His score on a nurse-rated Child
cent episode manic; ADHD, combined type; oppositional
Mania Rating Scale was similar to the parent-rated score
defiant disorder; reading and math disorder; and lan-
of 16. Depressive symptoms were not observed. Seth
guage disorder not otherwise specified. Since Seth
learned that there were consequences for his outbursts
clearly had more than bipolar disorder, attention to all
and was able to control them better. Seth’s mother was
of his challenges was necessary. He has remained stable
given the skills and backup needed to make it clear that
for a year but continues to need treatment. His mother
such behaviors would not be tolerated at home.
was advised that he indeed had bipolar disorder but that
Academically, Seth was woefully behind and needed a
medication continuation should be decided on a year-to-
less frustrating academic placement than the one he
year basis rather than worrying about the need for med-
ication for “the rest of his life.”
Seth had unequivocal symptoms of ADHD, which were
treated with mixed amphetamine salts since his mother
Eric’s Treatment and Follow-Up
was convinced that methylphenidate had made his be-
havior worse. This treatment reduced but did not elimi-
Eric’s parents were relieved to learn that he might not
nate his distractibility, impulsivity, and excessive talking.
have bipolar disorder and that ADHD is as heritable as bi-
After several weeks of gradual improvement, Seth’s be-
polar disorder (both have a heritability ratio of about 0.8
havior suddenly worsened. He became more disruptive
[38]). They understood that they had not caused Eric’s
at bedtime, and he responded explosively to any kind of
problem but had possibly exacerbated it, and they
limit. The positive relationship with his teacher became a
agreed that he needed a different medication approach,
Am J Psychiatry 166:1, January 2009 TREATMENT IN PSYCHIATRY
stability and consistency at home, and appropriate ex-
operationalize the accelerated energy, thinking, and hy- pectations and placement at school.
perhedonic activity that underpin mania. Seth was actu- Eric’s previous treatment trials suggested that medica-
ally observed to have such a period lasting several weeks tions had been adequately dosed and tried for reason-
during which he appeared different—that is, excessively able lengths of time. Thus, his lack of response to medi-
elated, even more explosive than previously, grandiose, cations was not due to poor management. The decision
and “constructively” energetic (in contrast to his back- was made to obtain behavior ratings of Eric’s ADHD
ground hyperactivity), with changes in sleep behavior.
symptoms and ratings of the frequency and severity of
outbursts while on his current regimen, and then to stop
Once these features were pointed out, his teachers and his his medications and observe him for deterioration; if
mother confirmed that they had occurred previously.
there was none, methylphenidate would be used alone
A case might be made that Eric also had an episode, initially. His behavior did not worsen appreciably off
starting around third grade, when his behavior worsened.
quetiapine and divalproex.
His aggression and frustration intolerance increased, but Although long-acting stimulant medications are usu-
he did not experience a simultaneous co-occurrence of ally preferred in order to avoid the need for an in-school
other manic symptoms. His ADHD was inadequately midday dose, Eric’s insurance would only cover the
treated, but his psychiatrist, concerned about his family much less expensive, short-acting form. Nevertheless, at
20 mg of methylphenidate three times a day, Eric’s be-
history of bipolar disorder, chose to initiate treatment for havior and academic performance in school improved.
He was also placed in a smaller classroom with more
Both Seth and Eric, even when treated with the best support for written work and for difficult behavior. His
medication and parent and school interventions, re- outbursts diminished but did not disappear, and his par-
mained somewhat symptomatic, which illustrates the fact ents now bore the brunt of these at home when the last
that we simply do not yet have completely effective treat- dose of his medication had essentially worn off (Eric
ments for many children with this constellation of symp- could not tolerate an evening dose). The addition of ari-
piprazole, more consistent child management tech-
niques, and the threat of hospitalization helped some-
In diagnosing bipolar disorder in children, it is neces- what, as did the fact that school was more satisfying and
sary to keep an open mind, and to continue to do so after that he had made a few friends. Eric’s referring physician
the first interview; ongoing observation is critical. A family continued to seek a medication that was as helpful in the
history of bipolar disorder is important but does not, in evening as methylphenidate was during the day. Eric’s fi-
and of itself, make a diagnosis. A full assessment, using nal diagnosis was ADHD, combined type; oppositional
defiant disorder; severe mood dysregulation; and disor-
multiple informants, is needed to address differential di- der of written expression.
agnosis, including learning and language disorders. Ulti-mately, it is important to understand the child, not just to Conclusion
There are important reasons why mania and severe Received July 30, 2008; revision received Sept. 14, 2008; accepted ADHD should be understood as different conditions.
Sept. 22, 2008 (doi: 10.1176/appi.ajp.2008.08091362). From the Di- However, from a therapeutic standpoint, the difference vision of Child and Adolescent Psychiatry, Stony Brook UniversitySchool of Medicine. Address correspondence and reprint requests to between mania and severe ADHD (plus aggression) is not Dr. Carlson, Director, Division of Child and Adolescent Psychiatry, in the use of atypical antipsychotics and mood stabiliz- Stony Brook University School of Medicine, Putnam Hall-South Cam- ers, both of which are supported by a substantial evi- pus, Stony Brook, NY 11794-8790; gabrielle.carlson@stonybrook.edu dence base for use in both disorders. Nor is it in the need Dr. Carlson has received research funding from Bristol-Myers to provide psychoeducation and specific parenting help Squibb, GlaxoSmithKline, Eli Lilly, NIMH, and Otsuka and has con- for families. There is a robust literature on behavioral treatment for ADHD and a growing literature on psycho-social treatments for bipolar disorder (39). Although theterms used to describe interventions to control dysregu- References
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