10
Editorial
Special Report
Category 1 CME
Expressive Arts Therapy
Substance Abuse and Addiction
Neurocognitive Impairment in Borderline Disorder?
,PsvchiatricTlmes
I . -.
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A CMPMedica Publication”
Issue Highlights
Integrative Management
of Anxiety
James Lake, MD
Treating Catatonia
in Autism
Max Fink, MD
Endocrine/Metabolic
EfYects of Antipsychotics
and Mood Stabilizers
Harold E. Carlson, MD and
Christoph U. Correll, MD
Neurobiology of PTSD
John J. Medina, PhD
Treatment for
Methamphetamine
Dependence
Kevin P. Hill,
MD. MHS
~
www.PsychiatricTimes.com
J a n u a r y 2008
~~~~~
Vol. MV.No.
11
Why Girls Starve Themselves:
New Research in Anorexia Nervosa
by Arline Kaplan
~
T
he November death of an Israeli
fashion model whose weight had
dropped below 60 Ib was chilling
even in a world that prizes rail-thin models as an ideal of feminine chic. Social
critics have long blamed the fashion industry’suseofsuchmodelsforinspiring
teenagers and young women to engage
in extreme dieting. But at the recent Annual Meeting of the California Psychiatric Association, in Huntington Beach,
eating disorders expert Walter Kaye,
MD, reminded attendees that the causes
of anorexia nervosa (AN)relate more to
genetics and neurobiology than to sizezero models on catwalks.’
While a perception persists that AN
and bulimia nervosa (BN) are culturally
detelnuneddisorders, anorexiapredates
our current culture, said Kaye, professor
of psychiatry and director of the eating
disorders program at the University of
California,SallDiego(UCSD). Hecited
anorexiasymptomsdescribedin 1689as
“newons consumption” by Sir Richard
Morton in his work. Plrthisiologitr, o r ( [
7 k r t i s e o f 1 Consurnp/iorr.
Despite our societal obsession with
dieting and weight, Kaye said, theprevalenceof:u1orexiasubtypesislow(0.25%
for AN-restricting type, and 0.25% for
AN-binge-eatingpurging type), which
indicates that factors beyond culture are
at work.
Sytnptomsexhibitedbypatientswith
AN can be puzzling, Kaye noted. They
seethemselvesas tat but seeotherpeople
with unorexin as thin. They tend to restrict their eating and have odd food
(Please see Anorexta Nervosa, page 6)
Medications for Agitation in Dementia:
Seeking Efficacy With Safety
by KennethJ. Bender. PharmD. MA
___
lnlost 3 years after the FDA
warned of increased mortality in
elderly patients who received
atypical antipsychotics off-label for neuropsychiatric syndromesofdementia, no
medication has been approved as safe
and effective for this increasingly challenging problem. Recent publications,
however, including a white paper from
the American College of Neuropsychophanuacology (ACNP). indicate that
clinical investigators are wrestling with
the dilenuna and considering potential
A
alternatives to antipsychotics.
“To prescribe or not to prescribe‘’ the
second-generationantipsychoticsforbehavioral symptoms in elderly patients
with dementia is the question posed by
DilipV. Jeste, MD. and Thomas Meeks.
MD,’in 1 of 3 conunentarieson this topic
in the October issue of the So[rtlwrrt
M~dicdJorrrrrtrl.Jeste is also lead author of the ACNP white paper, in which
he and colleagues acknowledge this
question as “a clinical conundrum for
which there are no immediate or simple
solutions.”’
The white paper laments the lack of
clinical trials with psychotropics i n older
adults in general and in those with dementia i n particular, “with consequent
lackofevidence-basedtherapeuticalternatives.” Alter the ACNP paper was issued, however. the NovenlberAfrrc.~ic,cIr,
.lorrrrrtr/ ofCcricrtric. Psyclritr/rp carried
the first head-to-head comparison of an
SSRl and a second-generntioll antipsychoticfornoncognitivesynlptolnsassociated withdementin.’
Bruce Pollock. MD, PhD. and colleagues found citnloprm (Celexn) and
risperitlone (Risperdal) to he cornpara(Please see Asitation in Dementia. uaae 81
www.psychiatrictimes.com
Anorexia Nervosa
Continued frompage 1
In This Issue
~.
~~
~
~~~~
-
EDl-rORlAL
Summoning the Muse:
The Role of Expressive Arts
Therapy in Psychiatric Care
CLINICAL ARTICLES
Ronald Pies, MD
Adverse Effects of
Antipsychotics and Mood
Stabilizers
DEPARTMENTS
~
Exposure to Violence
in Schools
Sheryl Kataoka, MD, MSHS
BOOK/DVD REVIEWS
The Lobotomist
Harold E. Carlson, MD and
Chrlstoph U. Correll, MD
Ronald Ples, MD
Brain Stimulation Therapies for
Treatment-Resistant Depression
Lewis’s Childhood and
Adolescent Psychiatry
David R. Block, MD
Arden 0. Dingle, MD
Healing Addiction
Darlene H. Moak, MD
WASHINGTON REPORT
Congress Expands JaiVPrison
Grant Programs, Moves to
Avert Medicare Cuts for 2008
Stephen Barlas
NEWS
Why Girls Starve Themselves:
New Research in Anorexia
Nervosa
Arline Kaplan
COLUMNS
INTEGRATIVE MEDICINE
Integrative Management
of Anxiety, part 2
James Lake, MD
CONVULSIVETHERAPY
Treating Catatonia in Autism
Max Fink, MD
MOLECULESOFTHEMIND
Neurobiology of PTSD, Part 1
John J. Medina, PhD
Medications for Agitation in
Dementia: Seeking Efficacy
With Safety
POETRY OFTHE TIMES
White Coat at Midnight
Kenneth J. Bender, PharmD, MA
Richard M. Berlln, MD
NCDEU Report, part 2
CHILD &ADOLESCENT
PSYCHIATRY
CATEGORY 1 CMEARTICLE
New Findings in Youth
Neurocognitive Impairment in
Borderline Personality Disorder? Anxiety %orders
Kenneth J. Bender, PharmD, MA
Jeannette LeGris, M H k and
Rob Van Reekum, MD
SPECIAL REPORT
SUBSTANCEABUSE
AND ADDICTION
Advances and Challenges in
Addiction Medicine
Mark J. Albanesa, MD
Culture and Substance Abuse
Patrick Abbott, MD
Duane M. Chase, MD
Anabolic Androgenic
Steroid Use
Lawrence M. Weisbeich, MD
Prescription Drug Misuse
in Youths
Oscar 6. Bukstein, MD, MPH
Treatment for Methamphetamine
Dependence
Kevin P. Hill, MD, MHS
Karen Dlneen Wagner, MD, PhD
PsychiatricTimesservesas an impartial forum for
informationaffecting mental health care professionals and their practices.The content of articles
(including lettersand book reviews)and the opinions expressed In PTare not necessarilyendorsed
byltseditors,editorialboard,orCMP.Toprotectpatlent confidentiallly,dlaloguesandpatientdescrlption represent a composite of patients, not a particularperson.
Unsolicitedmanuscriptswillbeconsidered,but can
only be returnedwhen accompaniedby a self-addressed stampedenvelope.
Copyright 0 2008 CMP Healthcare Media LLC.All
rights reserved. No part of this publicationmay be
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Darien. CT 06820. Periodicals postage paid at
Darien,CT,and additionaloffices.
choices, yet they also have an obsessive interest in diet, recipes, andcooking for others. They often exercise
compulsively, are anhedonic and ascetic, and find little in life rewarding
other than the pursuit of thinness.
Lack of insight on the part of individuals with AN makes it difficult for
clinicians toengagethemin treatment,
Kaye said.They do not see themselves
as having problems, do not learn very
well from experience, and do not think
logically.
Familystudies and
links to anxiety
Recent research, Kaye said, indicates
that biology plays a substantial role in
determining an individual’s vulnerability to an eating disorder. Family
studies show an increased rate of AN,
BN, and eating disorders not otherwise specified in first-degree relatives,
and the cross-transmission of AN and
BN in families.
Twin studies reveal that AN and BN
are highly heritable disorders (50% to
80%), so genes are more important
than culture or environment, Kaye
noted.
“One important new insight over
the past decade is that we have come
to realize there are traits people have
in childhood that put them at risk for
eating disorders,” Kaye said. “These
kids tend to be anxious, perfectionistic, and have an obsessive personality
and negative self-evaluation before.. .
an eating disorder [develops].”
While malnutrition may exaggerate the behavioral traits. Kaye noted
that the traits tend to persist after recovery. He described clinical studies
from 3 different continents showing
that between 60%and 80%of individuals with AN or BN have an anxiety
disorder during their lifetime and that
the onset of the anxiety disorder usually precedes the onset of the eating disorder. The most common anxiety disorders comorbid with AN and BN are
obsessive-compulsivedisorder(4 I %)
and social phobia(20%).?
Hypothesizing about the link between anxiety and AN, Kaye suggested that restricting or binge behavior
might be used as a means of reducing
dysphoric feelings.
Brain imaging
New brain imaging studies in AN,
using functional MRI (fMRI) and
positronemissiontomography (PET),
are enabling researchers to identify
and understand the brain circuits that
may contribute to such symptoms as
altered reward, anxiety, and appetite
modulation; altered body image; and
obsessiveness.
For example, several lines of evidence support the possibility that disturbances of dopamine function could
contribute to alterations of weight,
feeding behavior, motor activity, and
reward mechanisms in persons with
AN. Using PET scans, Frank and colleagues’ studied 10 women at least I
year after they recovered from AN.
Compared with 12 healthy control
subjects, they had significantly higher [“Clraclopride binding potential in
the basal ganglia’s anteroventralstriatum irrespective of their age, body
mass index, or time since recovery.
The researchers also found increased
dopamine D1and D, receptor activity
in another part of the basal ganglia
called the dorsal caudate, which was
related to anorexics’responses to and
avoidance of h a m . Such differences,
the research team concluded, might
explain why women with AN often exhibit exaggerated worry and concern
about what might happenin the future.
In addition,they said, individuals with
AN may haveadopamine-relateddisturbance of reward mechanisms that
contributes to their ascetic temperament and a lack of pleasure in eating
and other activities.
Another newly released study used
the fMRI approach to test the idea that
individuals with AN have differential
neural activation in primary and secondary taste cortical regions after sucrose and water administration. Individuals with AN often avoid normally
pleasurable foods and fail to appropriately respond to hunger.
In that study led by Wagner and
Kaye,’ the researchers looked at images of the brains of 16 women who
had recovered from AN and of 16
control subjects. They measured their
brains’ reactions to pleasant taste (sucrose) and neutral taste (distilled
water). Compared with the control
group, individualswho had recovered
frotnAN showed a significantly lower
neural activation in the insula, including the primary cortical taste region
andventral anddorsal striatum, toboth
sucrose and water. In addition, insular
neural activity correlated with apleasantness rating for sucrose in the control group but not in the recovered AN
group. The results of the study are the
firstevidence that individuals with AN
process taste in a different way from
those without aneatingdisorder.
Just last month, Wagner and associates’ published results from another
M R 1 study to assess the response of
the anteroventral striatum to reward
and loss in persons with AN. They
used event-related fMRI to examine
the blood oxygen level-dependentsignal while participants (13 women
who had recovered from AN and I3
PSYCHIATRICTIMES
71
www.psychialrictimes.com
healthy comparison women) performed a simple choice and feedback
test. Incontrast to the healthy controls,
the wonlen who had recovered from
AN showed greater activation of the
dorsal caudate and did not differentiate between reward and punishment in
the anteroventral striatum limbic circuits. On the basis of these findings,
the researchers concluded that individuals with AN have an impaired
ability to identify the emotional signilicance o f a stimulus but have increased traffic in neural circuits that
are concerned with planning and
consequences.
antidepressants and neuroleptics“without a lot of proof that they were
actually successful,”-as well as providing treatment in structuredsettings.
Relapse rates were high.
Goals for the second generation of
treatment, Kaye said, includepreventing relapse; developing specialized,
effective psychotherapies; using controlled trials to identify useful medications: and treating patients without
hospitalization.
We are not there yet, he said, because “we have not understood the
r-
I Maudsley treatment focuses on
Treatment approaches
Over time, many people recover from
AN and BN, Kaye said, with as many
as 50% to 70% getting better in their
20s. Still.30~ofindividualswithAN
remain chronically ill and 10%die of
the disorder, making it the psychiatric
disorder with the highest
- mortality
rate. Weight restoration is very important in the short run, to keep patients
from starving t o death, but many patients continue to have symptoms.
Developing more effective treatments for acute symptoms is fixstrating, Kaye added. The first generation
of treatment involved weight restoration, using behavior modification,
persons with AN, Kaye said. In one
study, CBT was evaluated as a posthospitalization treatment for AN in
adults and was found to be more effective than nutritional counseling in improving outcome and preventing relapse.R
Family-based therapies appear
promising, Kaye said. The familybasedMaudsley treatment, developed
in England, appears to be effective
early in the course of the illness. The
treatmentfocusesonsymptomsrather
than blame and takes a nonauthoritarian therapeutic stance in which the
family is made responsible to re-feed
the child.
TheNIMH is supportinga6-center
study (including UCSD) of persons
aged 12to 18 years who have AN. The
study will compare the Maudsley
treatment with psychodynamic family therapy and fluoxetine with placebo. Maudsley family therapy already
has become an integral part of the intensive family-based treatment prodividuals with ANoftenreadabout the gram f o r m at UCSD, one of the first
weight gain that canbe associatedwith of its kind in the country.
Unfortunately, communities often
atypical antipsychotics and then refuse to take them.
do not have a therapist or program SFcialized in the treatment of AN, so inRole of Maudsley treatment
dividuals end up being sent to a resiFewcontrolledstudieshavebeendone dential treatment facility, usually at
so far on the use of psychotherapy for
(Please see Anorexia Nervosa, page 8)
patients were randomized to receive
fluoxetine (Prozac) or placebo for up
to 1 year along with cognitive-behavioral therapy (CBT), no benefit forfluoxetine was shown over placebo.’
While some modest improvement
in persons with AN (weight gain, reduced agitation, less treatment resistance) has been seen in case reports
and open trials with atypical antipsychotics,suchasolanzapine(Zyprexa),
risperidone (Risperdal), orquetiapine
(Seroquel),controlledtrialsareneeded. In any case,Kaye has found that in-
I
symptoms ratherthan blame and
takes a nonauthoritarian therapeutic
stance in which the family is made
responsible to re-feed the child.
pathogenesis and physiology of these
illnesses. Until we do that, it is hard to
come up witheffective treatments.”
Drugs do not improve weight restoration very much. Kaye said, but
SSRIs may prevent relapse in some
peopleafterweightrestoration.6However, in a recent study’ in which out-
~~
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www.psychiatrictimes.com
Anorexia Nervosa
igitation in Dementia
Continued hrn page 7
ontinued Fmm page 1
some distance, making family involvement with treatmentdifficult.To
address this issue, a new treatment
program at UCSD has the individual
with AN, the siblings, and the parents
stay a t a nearby residential hotel for
about a week. The 40-hour program
consists of a comprehensive medical
and psychological evaluation of the
patient:illtensivepsychoeducatiollfor
the entire family. including a discussion ol‘the symptoms and causes of
AN; a5-sessionilltroductionto Maudsley family therapy; other treatments;
and discharge planning
“Before they return to their home
states, we do a consultation with the
patient‘s home therapist or physician
regarding follow-up care,” Kaye said.
“We have had some good success with
this new approach.”
de in their effect on behavioral and
lsychotic symptoms. The finding of
omparable effect from agents with
lisparate mechanisms, they suggest,
nay contribute to the understanding of
mderlying pathophysiology. “Neurohemical data consistently point to donnunergic deficits in dementia,” Polock and colleagues said, “casting
loubt about the rationale for using
)2-blocking agents in these patients.
n contrast, serotonergic deficits are
tronglyassociatedwithimpulse-conrol disorders and aggression.”
References
1. Kaye W. Why do they keep doing it? How the brain
drives thoughts and behaviors in anorexia nervosa.
Presenled at: 19th Annual Premier Conference of the
CaiiforniaPsychiatricAssociation;October5-7,2007;
HuntingtonEeach.Calif.
Z.KayeWH.EulikCM,ThorntonL,etal.Comorbidityof
anxiety disorderswith anorexia and bulimia newosa.
ArnJPsychiaby2004;161:2215-2221.
3.FrankGK.EailerUF,HenrySE,etal.lncreaseddopamine D / O receptor binding after recovery from
anorexi: nlrvosa measured by positron emission tomography and [“clraclopride.BiolPsychiaty 2005;
58.908-912.
4.WagnerA,AizensteinH.MazurkewiczL,etal.Altered
insula response to taste stimuli in individuals recovered from restricting-type anorexia nervosa. Neuropsychopharmacology 2007 May 9;[Epub ahead of
print].
5. Wagner A, Aizenstein H. Venkatraman VK. et ai. Altered reward processing in women recovered from
anorexianervosa.ArnJPsychiaby.2007:164:18421849.
6. Kaye WH, Nagata T, Welkin TE. et al. Double-blind
placebo-controlledadministration of fluoxetine in restricting- and restricting-purging type anorexia nervosa. BiolPsychiaby 2001;49:644-652.
7. Waish ET, Kaplan AS, Attia E, et al. Fluoxetine after
weight restoration in anorexia nervosa:a randomized
controlledtrial.JAMA.2006295:2605-2612.
8. Pike KM, Walsh BT,Vitousek K, et al. Cognitive behavior therapy in the posthospitaiizationtreatment of
anorexia nervosa. Am JPsychiaby 2003;160:20462049. fl
Opinionated
PsychiatristsWanted
Psychiatric 7intes invites readers
to suggest Commentaries and
PointlCounterpoint articles. Topics should be relevant to practicing psychiatrists and mental
health care professionals. Pointl
Counterpoint issues should have
2 distinct viewpoints with a corresponding author for each. Proposals andarticles shouldbegrounded
in scientific literature and include
references. Send proposals to:
PTEdit@cmp.com.Please note
that manuscripts may be sent for
peer review. 0
I n indication awaiting
nedication
n the editorial accompanying the
italopram-risperidone comparative
rial, Clive Ballard, MD,1 notes the
lressing need [or safe, effective treatnent of the aggression and nonagyessive agitation that occurs in about
!O% of patients with Alzheimer dis:ase in the community and in about
LO% to 60% of these patients in care
‘acilities. Although hallucinations
lave been found in prospective studes to often resolve over a few months,
3allard points out that delusions and
lgitation are more persistent.
Ballard noted that behavioral probems develop in 90% of people with
lementia during their illness. “These
symptoms are frequently distressing
‘or the patients who experience them,
Ire problematic for their caregivers,
md often precipitate institutional
:are.”
Atypical antipsychotics have gen:rally replaced olderantipsychotics in
&label use for dementia-relatedbehavioral symptoms in the elderly be:ause of their advantages of less anti:holinergic effect and liability for
tardive dyskinesia. This trend came
intoquestion,however, with theemergence of other adverse effects, particularly metabolic, and with mixed results fromefficacy studies.’
The trend toward using secondgeneration antipsychotics forthis population was further disrupted by FDA
warnings of stroke associated with
risperidone, olanzapine (Zyprexa),
and aripiprazole(Abilify),as wasevidenced in a meta-analysis of 11 trials
with risperidone or olanzapine and 3
with aripiprazole.5AsubsequentFDA
warning in2005 associatedallsecondgeneration antipsychotics witha 1% to
2% increased mortality rate (a 4.5%
mortality rate among patients who received antipsychotics vs 2.6% with
placebo in 17 short-term trials).b
In addition to adverse effects, second-generation antipsychotics have
shown no more than modest efficacy
for patients with dementia in metaanalyses of clinical trials and in the
risperidone, whilediscontinuationbecause of adverse events favored placeIargeCATIE-AlzheimerDisease(AD) bo. Dementia patients with neurostudy. In a meta-analysis of trials be- psychiatric disturbances other than
fore the CATIE-AD, including a total psychosis did better with the antipsyof more than 3300 patients with de- chotics than did those with psychotic
mentia, there was a statistically small symptoms.
Although the FDA warnings on
effect size in symptom rating scale
scores, supportingevidence of effica- cerebrovascular events and mortality
cy of aripiprazole and risperidone but rates were specific to the second-gennot of olanzapine; and insufficientdata eration antipsychotics, there is evito ascertain efticacy of quetiapine.’ dence that the first-generationantipsyIn theCATIE-ADstudy, withmore chotics are no safer. A retrospective
than 400 patients, olanzapine, queti- population-based cohort study with
apine, and risperidone were not sig- more than 27,000 matchedpairsfound
nificantly better than placebo in the a higher risk of death with these neuprimary outcome of time to discon- roleptics at all monthly points in the
tinuation.’Discontinuationforlackof 4- non nth study period.*Anotherretroefticacy did favor olanzapine and spectivestudy, published shortly after
Mental Problems in
Returning Vets:
Delayed Testing
Shows Higher Rates
Many veteransface mental illnesses
onretumfromduty,butforhowlong
and to what extent? Psychiatrist
Charles S. Milliken and colleagues
are on a mission to measure the mental health needsofreturningsoldiers
from Iraq, including soldier assessment and use of mental health care,
using 2 surveys-the Post-Deployment Health Assessment (PDHA)
and the Post-Deployment Health
Reassessment (PDHRA). The results oftheiranalyses werereported
in the November 2007 issue of
JAMA .
To identify mental health concerns among soldiers, the Department of Defense administers the
PDHA almost immediately on return from deployment. However,
this raisesconcernsthatcertain mental health issues (such as posttraumatic stress disorder [PTSD], depression, and alcohol abuse
disorder) may be overlooked because of the screening’s timing.
Therefore, the Department of Defense introduced a second assessment, the PDHRA, to be administered 3 to 6 months after soldiers’
return.
The PDHRA is administered
using a self-report questionnaire followedbyabriefinterviewwithaprimary care physician, physician assistant, or nurse practitioner. Upon
completion, theclinicianreviewsthe
answers and is directed to use his or
her judgment in determining who
needs a referral for further evaluation. The results of both the PDHA
and PDHRA become part of a sol-
dier’s pennanent medical record and
part of the Defense Medical Surveillance System.
A total of 88.235 soldiers were
accounted for in this analysis;90.8%
were men, 58.2% were married, and
the mean age was 30.4years. Active
(n=56,350)andNationalGuardand
Reserve (n = 31,885) soldiers’ results were separated.
As expected, soldiers indicated
more mental health distress on the
PDHRA than on the PDHA and
were referred at higher rates following administration of the PDHRA.
Of the symptoms, concerns about interpersonal conflict increased the
most (3.5% to 14% active; 4.2% to
2 I . 1% reserve). In addition. PTSD,
depression, and overall mental
health risk also increased in both
groups; 6669 Active soldiers
( I 1.8%) endorsed alcohol misuse.
Of the total, 3925 (4.4%) were referred for mental health care on the
basis of the PDHA. and 10,288
( I 1.7%) were referred on the basis
of the PDHRA-a sharp increase.
Among National Guard and
Army Reserve soldiers,referrals for
mental health concerns were substantially higher on the PDHRA
than they were for active soldiers
( 3 6 . 2 % 14.7%).Theyalsoreport~~
ed more health concerns and were
referred at higher rates for any health
concern(20.8%vs 16.58).
The authors concluded that the
rates detennined on the basis of the
PDHA“substantia1lyunderestimate
the mental health burden.”They note
that the combined PDHA and
PDHRA screening identified 20.3%
to 42.4% of soldiers requiring mental health treatment, which is similar
to the reported rates at Veterans Affairs facilities. fl
-Corrrlq M m r s