insights - cleveland clinicprofile in brain regions but suffers from long data acqui-sition times....

Insights 2013A publication of the Center for Behavioral Health

Whole Brain 3-D Magnetic Resonance SpectroscopyNew Windows into the Abnormalities Underlying Neuropsychiatric DiseaseSee page 4

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Insights 2013

In tHIS ISSue

neuRoIMAgIng In PSYCHIAtRIC DISeASe

4 Whole Brain 3-D Magnetic Resonance Spectroscopy: Advancing the exploration of neuropsychiatric Disorders — Amit Anand, MD, and Pallab K. Bhattacharyya, PhD

CLInICAL tRIALS In ALZHeIMeR DISeASe

7 ‘Multiple Shots on goal’ Strategy Aims to empower Patients Against Alzheimer Disease — Jeffrey Cummings, MD, ScD, and Kate Zhong, MD

PSYCHo-onCoLogY

10 Psycho-oncology update: Innovating an Approach to Systematic Distress Screening in Patients with Cancer — Beth Gardini Dixon, PsyD, and Isabel Schuermeyer, MD

funCtIonAL IMAgIng In neuRoPSYCHIAtRY

12 Magnetoencephalography Provides new Window into Brain Connectivity Across Diverse neuropsychiatric Conditions — Patricia Klaas, PhD, and John C. Mosher, PhD

ADDICtIon MeDICIne

14 Medication-Assisted treatment with Suboxone: finding Success with a nontraditional Approach to opiate Dependence — Jason M. Jerry, MD

BRAIn StIMuLAtIon In neuRoPSYCHIAtRIC DISeASe

16 Development of Innovative technologies for Brain Stimulation: going Microscopic to overcome earlier Limitations — John T. Gale, PhD

IntenSIve outPAtIent tHeRAPY

19 outcomes Collection effort Showcases value of an evolving Intensive outpatient Program — Daniel Jones, PhD

PSYCHIAtRY eDuCAtIon

21 Medical Students and the eMR: Improving the educational experience by tailoring templates — Margo C. Funk, MD

PeDIAtRIC BeHAvIoRAL HeALtH

24 early Intensive Behavioral Intervention for Autism Spectrum Disorders Maximizes Mainstream educational Placements — Thomas W. Frazier II, PhD

BeHAvIoRAL HeALtH In CARDIovASCuLAR DISeASe

26 Hearts and Minds: offering Behavioral Health Services in a Cardiology Clinic to Boost Patients’ Spirits — and Outcomes — Leo Pozuelo, MD, and Leslie Cho, MD

ADoLeSCent PSYCHIAtRY

28 electroconvulsive therapy: underutilized Modality Can Be Safe, effective for Severe Mood Disorders in Adolescents — Joseph Austerman, DO

ALSo InSIDe

31 Staff Listing

32 Resources for Physicians

on tHe CoveR: three-dimensional maps of brain metabolites using a high- spatial-resolution 3-D PePSI pulse sequence. See article on page 4.

Dear Colleagues,

Donald A. Malone Jr., MD

Medical Editor

glenn Campbell

Managing Editor

Anne Drago

Art Director

Insights is published by Cleveland

Clinic’s Center for Behavioral Health to

provide the latest information about the

center’s clinical services and research.

Insights is written for physicians and

should be relied on for medical educa-

tion purposes only. It does not provide

a complete overview of the topics

covered and should not replace the

independent judgment of a physician

about the appropriateness or risks of a

procedure for a given patient.

the Center for Behavioral Health is part

of the multidisciplinary Cleveland Clinic

neurological Institute, which is dedi-

cated to the diagnosis and treatment of

common and complex neurological dis-

orders of adult and pediatric patients.

Its more than 300 specialists combine

expertise and compassion to achieve

measurably superior results. By

promoting innovative research and care

models, the neurological Institute ac-

celerates development and application

of new treatments and technologies to

patient care. the neurological Institute

is one of 27 institutes at Cleveland

Clinic, a nonprofit academic medical

center ranked among the nation’s top

hospitals (U.S. News & World Report),

where nearly 3,000 physicians in 120

specialties collaborate to give every pa-

tient the best outcome and experience.

clevelandclinic.org

Psychiatric research and discovery have deep roots at Cleveland Clinic. Did you know

that in 1948 researchers here were the first to isolate a batch of a substance in blood that

we know today as serotonin?1 Those Cleveland Clinic researchers gave the substance its

name, to reflect its presence in blood serum (sero) and its effect on vascular tone (tonin).

While the early characterization of serotonin sets a high bar for research achievement,

today’s clinicians and researchers in Cleveland Clinic’s Center for Behavioral Health are

committed to upholding that legacy, as demonstrated by the diverse research initiatives

profiled in this issue of Insights. Here are a few examples:

• Inourcoverstory,Drs.AmitAnandandPallabBhattacharyyaoutlinetheinsights

they are gaining through whole brain 3-D magnetic resonance spectroscopic imaging

and how they plan to build on these insights with Cleveland Clinic’s new 7-tesla (7T)

MRIscanner,whichourNeurologicalInstituteacquiredinmid-2013.

• Onpage7,Dr.JeffreyCummings,oneoftheworld’spremierAlzheimerdisease(AD)

researchers, and Dr. Kate Zhong share the rationale and potential benefits of the

nearlymatchless“multipleshotsongoal”ADresearchstrategythey’veputinplace

at Cleveland Clinic Lou Ruvo Center for Brain Health.

• Onpage12,Drs.PatriciaKlaasandJohnMosherexplainwhyandhowtheyarelever-

aging Cleveland Clinic’s highly prolific magnetoencephalography (MEG) laboratory

to pursue innovative MEG research in multiple neuropsychiatric applications.

• Onpage16,Dr.JohnGaleupdatesusonpromisingworkhisgroupisdoingtoover-

come limits of current brain stimulation methods with a novel modality known as

microscopic magnetic stimulation.

Inbetweentheseandotherresearchprofilesarereportsofmanynotableclinicalactivi-

ties across our center, from an innovative tool to systematically screen for psychosocial

distress in cancer patients to our nontraditional but highly successful approach to treat-

ing opiate dependence.

We intend this publication as a launching pad for dialogue with you, our colleagues

aroundthenation.Ifyouseesomethingofinterest,don’thesitatetocontactmeormy

colleagues featured within to continue the exchange.

Sincerely,

DonaldA.MaloneJr.,MD

Director, Center for Behavioral Health

Chairman, Department of Psychiatry and Psychology

President, Lutheran Hospital

[email protected]

RefeReNCe

1.RapportMM,GreenAA,PageIH.Serumvasoconstrictor,serotonin;isolationandcharacterization. J Biol Chem.1948;176(3):1243-1251.

© the Cleveland Clinic foundation 2013 CLeveL AnD CLInIC CenteR foR BeHAvIoRAL HeALtH | 866.588.2264 3

Whole Brain 3-D Magnetic Resonance Spectroscopy

MRSI,alsoknownaschemicalshiftimaging,records

spectroscopicdataforagroupofvoxelsusinganMRI

scanner. To date, attempts to characterize the neuro-

biological basis of psychiatric illness have used proton

MRSItononinvasivelymeasuretheneurochemical

environment within the brain. The neurochemicals most

commonly visualized are:

• Lactate

• ThemetabolitesN-acetylaspartate(NAA),creatine(Cr)

and choline (Cho)

• Theaminoacidsγ-aminobutyricacid(GABA),glutamate

and glutamine

Asimagingtoolsarerefined,knowledgeofbrainneu-

rochemistry in neuropsychiatric disorders will expand,

promising better disease detection, superior therapy

monitoringandimproveddrugdevelopment.New

imagingmethodsandtechniquestomapmetabolites

in larger volumes of the brain are being developed to

accomplishthesegoals.Advancesinhardwareandpulse

sequenceshavealreadymadeitpossibletoscanamuch

larger portion of the brain in three dimensions (3-D) with

good signal-to-noise ratio and in reasonable scan time.1-3

This article highlights the advantage of building on

theseadvancesbyperforming3-DMRSItogainclinical

insights and discusses the potential for future insights

withtherecentarrivalofa7-tesla(7T)MRIscannerat

Cleveland Clinic.

Whole Brain 3-D Magnetic Resonance Spectroscopy: Advancing the exploration of neuropsychiatric Disorders

By Amit Anand, MD, and Pallab K. Bhattacharyya, PhD

n E u R o i M A G i n G i n P S y C H i A t R i C D i S E A S E

Figure 1. Single-slice spectra of N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) using three-dimensional proton echo-planar spectroscopic imaging (PEPSI). A total of eight slices were scanned for this study.

Mapping biochemical information in the brain has the potential to unlock the biochemical processes involved in neu-

ropsychiatric disorders, which remain poorly understood. Although techniques such as proton magnetic resonance

spectroscopy (MRS) have yielded insight into the workings of the brain, these techniques are mostly restricted to

single voxels (to obtain relatively large signal over a homogeneous area of brain) and thus to small areas of the brain

that sometimes may not be relevant to psychiatric illness. in addition to single-voxel spectroscopy, multivoxel MR

spectroscopic imaging (MRSi) has long been used in spectroscopy studies, but MRSi studies often scan over a single

slice and require long scan times to obtain useful information.

4 inSiGHtS | 2013 CLeveL AnDCLInIC.oRg /PSYCHIAtRY


Abnormalitiesinconcentrationsofthesemetabolites

are indicators of abnormal neuronal energy metabolism,

which is known to occur in several neuropsychiatric

disorders. For technical reasons, a single-voxel design

that allows signal detection from a well-defined area and

requiresshortermeasurementtimestypicallyhasbeen

employed. Unfortunately, measuring localization limits

measurement to brain areas that may not be involved in

psychiatric illness (e.g., the occipital cortex) and therefore

does not provide a meaningful and comprehensive

picture of whole brain metabolite concentrations.

Althoughacquisitiontimesareshorterwithsingle-voxel

spectroscopy, that approach is best suited to imaging

when a volume of interest is known. Multivoxel spectro-

scopicmethodscanpresentdatain2-Dor3-Dimages.

Multivoxel spectroscopy is able to identify the metabolite

profileinbrainregionsbutsuffersfromlongdataacqui-

sition times.

Building on insights from 2-D Studies

Inarecentstudy,Dr.Anandandcolleagues,4 using a sin-

gle-slice2-Dtechnique,reporteddifferentconcentrations

of glutamate in different brain regions among patients

with bipolar depression, patients with bipolar mania and

healthy controls, whereas concentrations of lactate were

uniformly high in all regions.

Thisdiscoveryhasignitedaquesttostudychemical

changes in large volumes of brain simultaneously. By

using 3-D proton echo-planar spectroscopic imaging

(PePSI),brainmetabolitescanbemeasuredsimultane-

ously from multiple brain regions to accelerate spectra

acquisitiontimes.Usingahigh-spatial-resolution3-D

PePSIpulsesequenceat3Tfieldstrength,high-quality

spectra of the metabolites from a large part of the brain

were obtained (Figure 1). The scan also generated excel-

lent3-DmapsofNAA,CrandCho(figure2).

Figure 2. Three-dimensional maps of N-acetylaspartate, creatine and choline using a 3-D PEPSI sequence.

n-Acetyl Aspartate

Creatine

Choline

CLeveL AnD CLInIC CenteR foR BeHAvIoRAL HeALtH | 866.588.2264 5


new opportunities with 7t MRi Scanner

ClevelandClinic’sCenterforNeuroimagingrecently

acquireda7TSiemensMRIscannertoconductstate-of-

the-artMRI/MRSstudies,makingoursoneofthefirst

institutionstousea7TMRIscannerinaneuropsychiat-

ric research setting. The advantages of MRS at 7T include:

• Ahighsignal-to-noiseratiotoenhanceimagequalityby

decreasing voxel size

• Improvedspatialresolutionrelativetoothernoninvasive

imagingtechniques

WewillbeworkingtodevelopMRSIsequencessuited

for ultra-high fields to take advantage of the increased

spatial and spectral resolution they provide.

With our new ability — made possible by ultra-high field

strengths — to map metabolite distribution in the entire

brain, we hope to gain further insight into the pathophys-

iology of neurological and psychiatric disorders. n

KEy PointS

Magnetic resonance spectroscopy (MRS) provides an invaluable tool to noninvasively study the neurochemis-try of the living brain in neuropsychiatric disorders.

Whole brain 3-D MRS imaging could potentially be an extremely important tool to study the distribution and concentration of metabolites in the whole brain, provid-ing a comprehensive picture of what abnormalities may underlie neuropsychiatric disorders.

7t MRI scanners offer improved signal-to-noise ratio and faster imaging to facilitate whole brain study, over-coming limitations of traditional MR imaging modalities in neuropsychiatric disease. Cleveland Clinic is one of the first institutions to use a 7T scanner in a research setting to study brain neurochemistry in neuropsychiat-ric disorders.

RefeReNCeS

1.MaudsleyAA,DomenigC,GovindV,etal.Mappingofbrain metabolite distributions by volumetric proton MR spectroscopicimaging(MRSI).Magn Reson Med. 2009;61(3):548-559.

2.PosseS,OtazoR,DagerSR,AlgerJ.MRspectroscopicimaging: principles and recent advances. J Magn Reson Imaging.2013;37(6):1301-1325.

3.OtazoR,TsaiSY,LinfH,PosseS.Acceleratedshort-Te3D proton echo-planar spectroscopic imaging using 2D-SeNSewitha32-channelarraycoil.Magn Reson Med. 2007;58(6):1107-1116.

4.XuJ,DydakU,HarezlakJ,NixonJ,DzemidzicM,GunnAD,KarneHS,AnandA.Neurochemicalabnormalitiesinunmedicatedbipolardepressionandmania:A2D1HMRS investigation. Psychiatry Res Neuroimag. 2013;213:235-241.

Dr. Anand is Vice Chairman for Research and Director of the

Mood Disorders Clinical and Research Program in Cleve-

land Clinic’s Center for Behavioral Health and Department

of Psychiatry and Psychology. His specialty interests include

mood and bipolar disorders, depression, brain imaging,

clinical psychopharmacology and personalized medicine.

He can be reached at 216.636.2840 or [email protected].

Dr. Bhattacharyya is an assistant staff member in the

Department of Diagnostic Radiology, Imaging Institute,

and in the Mellen Center for Multiple Sclerosis Treatment

and Research, Neurological Institute. He can be reached at

216.444.5364 or [email protected].


C l i n i C A l t R i A l S i n A l z H E i M E R D i S E A S E

CLeveLAnD CLInIC Lou Ruvo CenteR foR BRAIn HeALtH:

‘Multiple Shots on goal’ Strategy Aims to empower Patients Against Alzheimer Disease

By Jeffrey Cummings, MD, ScD, and Kate Zhong, MD

CurrenttreatmentsforAD,whichincludecholinesterase

inhibitors and memantine, offer temporary symptomatic

benefit. They improve cognition, function and behavior

in some patients and delay disease progression in most.

They do not modify the underlying disease process. There

is an urgent need to identify disease-modifying therapies

thatwillpreventAD,delayitsonsetorslowitsprogres-

sion.Inaddition,newagentsareneededtofurther

improveAD’ssymptomaticmanifestations.

Morethan80agentsarecurrentlyinclinicaltrialsforthe

treatmentofsomephaseofAD,includingnoveldisease-

modifying and symptomatic treatments. Cleveland

Clinic Lou Ruvo Center for Brain Health (LRCBH) has

one of the largest clinical trials programs in the United

StatesforADtherapeutics.Ourinnovativemultisite

organization, detailed below, helps develop strategies to

transformtheclinicaltrialsprocess,improvethequality

oftrialsanddevelopnewtherapiesforAD.

Addressing the Pathophysiology of AD

ThemolecularneurobiologyofADisincreasinglywell

understood.Amyloidproteinabnormalitiesinthebrain

are among the first identifiable biological changes in

the disease and are manifested by a reduction in beta

amyloid levels in the CSF and deposition of amyloid

in the brain on amyloid imaging (Figure 1). There is

increasingcelldeathasADprogresses,withlibera-

tion of tau protein into the spinal fluid and exposure of

intercellular neurofibrillary tangles to the CSF, leading

to increases in CSF tau and hyperphosphorylated tau

(p-tau).Neurodegenerationalsoleadstoincreasing

atrophyonMRI.Cerebralmetabolismiscompromised,

as demonstrated by reduced cerebral metabolic activity

on FDG-PET studies. There are biomarkers for the major

milestonesofAD.

Multiple Shots on Goal

Approximately95percentofdrugsaddressingCNS

diseases fail, and disease-modifying interventions have

proved particularly difficult to develop.2 To advance

therapies, it is important to have “multiple shots on goal”

since only a very few test agents become successful drugs.

With this in mind, the LRCBH has developed a balanced

matrix type of clinical trials program, with agents target-

ing multiple disease stages in a variety of formulations

andwithdiversemechanismsofaction(figure2).

Multiple treatment options are being assessed to match

patients’ needs and preferences, from immunotherapies

administered by intravenous or subcutaneous injection

to oral medications to device-based therapies such as

transcranialmagneticstimulation.Dextromethorphan/

quinidine(Nuedexta™)isbeinginvestigatedforits

potential impact on agitation, while other interven-

tions are being assessed for cognitive and functional

outcomes.Anti-amyloiddisease-modifyingtherapies,

non-amyloid targeted disease-modifying therapies and

symptomatic interventions are all being assessed by the

LRCBH clinical trials program (Figure 3).

Empowering Patients

ThefDA’srequirementthatnewtherapieshavetheir

efficacy demonstrated by randomized, placebo-con-

trolledtrialsbeforeapprovaliswellestablished.Oneof

its underappreciated implications is that patients must

be engaged in the drug development process in order for

The challenge posed by Alzheimer disease (AD) is stark: If no means of preventing or delaying AD is identified, the

number of Americans suffering from the disease is projected to rise from 5.3 million today to over 13 million by 2050.1

Figure 1. Amyloid imaging scans show contrasting findings in a patient with Alzheimer-type dementia, with heavy amyloid deposition (left), and in a healthy control subject of similar age (right).



it to succeed. Patients are thus empowered to contrib-

ute in an essential way to the development of therapies

for the diseases that afflict them. This motivation is

strengthened by the realization that the children and

grandchildren of affected individuals are at increased

riskforADunlessnewinterventionsarefound.

The scope of the LRCBH’s clinical trials program signals

ourcommitmenttoofferingADpatientsbroadoppor-

tunitiesforsuchempowerment.Oneofthewayswe

do so is through a network of trial sites with extensive

nationalreach.TheLRCBHhaslocationsinLasVegas,

Nev.;atClevelandClinic’smaincampusinCleveland;in

Lakewood,Ohio,outsideofCleveland;andinWeston,

fla.ThesesitesformauniqueADclinicaltrialsconsor-

tium that matches patient location with available studies.

The consortium amplifies our ability to engage multiple

patients in clinical trials and accelerate therapeutic

testing,anditpromisestoimprovetrialqualityand

efficacy.

impacting trial Methodology

AleadinggoaloftheLRCBHclinicaltrialsprogramis

to transform trials by identifying methodologies that

improvequalityandacceleratedrugdevelopment.Recent

LRCBH publications address important issues that

impactdrugdevelopmentforAD.Globalizationisoccur-

ring rapidly, but the science of globalization remains

poorly developed.3Avarietyofclinicaltrialdesignshave

alsobeenfostered,bothforADandfornon-ADneuro-

degenerativedisorders.ArecentreviewfromtheLRCBH

highlighted the importance of matching the design

of a clinical trial to the trial’s goal.4 Studies of placebo

groups recently showed that older patients in clinical

trials decline more slowly than younger patients.5 This

has important implications for sample size determina-

tions since a larger number of older patients would be

needed to show a drug-placebo difference compared

with trials enrolling younger subjects. Recent reviews

from the LRCBH have addressed the translation of data

from animal models to human clinical trials,6 use of

repurposedagentstotreatAD7 and use of translational

research methodologies to enhance drug development.8

Summary

AsADprevalencecontinuestoriseatanalarmingrate,

new therapies are urgently needed. The LRCBH is testing

multiple diagnostic and therapeutic interventions in a

balanced matrix approach with a multiple-shots-on-goal

philosophy.Ourdistributednetworkofclinicaltrialsites

utilizing the geography of Cleveland Clinic is an innova-

tive advantage for clinical trials and drug development.

Ourapproachrecognizesthattrialsdependonpatients

acting as citizen-scientists who empower themselves to

help fight the diseases that afflict them. n

Prevention Prodromal AD AD Dementia

ADnI ADnI ADnI

Professional fighters Study Aclarus Dx® blood test Aclarus Dx blood test

Pioglitazone MK-8931 MK-8931

Immunotherapy ACC-001 Immunotherapy ACC-001

Immunotherapy BIIB037

Immunotherapy MABt5102A

Immunotherapy IvIg

Bexarotene

Resveratrol

DM/Q (agitation)

transcranial magnetic stimulation

AC-1204

Amyloid imaging

Biomarker study

Disease-modifying treatment

Symptomatic treatment

Figure 2. Balanced matrix of therapeutics and diagnostics being assessed in the LRCBH clinical trials program. Agents/studies are grouped according to whether they represent prevention approaches in patients with normal cognition, drugs addressing mild cognitive symptoms in patients with prodro-mal AD, or drugs for more severe behavioral and cognitive symptoms in patients with Alzheimer dementia. ADNI = Alzheimer’s Disease Neuroimag-ing Initiative; DM/Q = dextromethorphan/quinidine.



KEy PointS

Clinical trials can empower patients to help overcome the diseases that afflict them and, in the case of AD, threaten their children and grandchildren.

Cleveland Clinic Lou Ruvo Center for Brain Health (LRCBH) has one of the nation’s most active clinical trials programs for AD, with a repertoire of disease-mod-ifying and symptomatic approaches under investigation for patients at risk of AD and those with prodromal AD or AD dementia.

the LRCBH’s distributed network of clinical trial sites takes advantage of the wide-ranging geography of Cleveland Clinic to expand patient access to investiga-tional therapies and accelerate therapeutic testing.

RefeReNCeS

1.Alzheimer’sAssociation.2013Alzheimer’sdiseasefactsand figures. Alzheimers Dement.2013;9:208-245.

2.BeckerRe,GreigNH.WhysofewdrugsforAlzheimer’sdisease?Aremethodsfailingdrugs?Curr Alzheimer Res. 2010;7:642-651.

3.CummingsJ,ReyndersR,ZhongK.GlobalizationofAlzheimer’sdiseaseclinicaltrials.Alzheimers Res Ther. 2011;3:24-33.

4.CummingsJL,GouldH,ZhongK.AdvancesindesignsforAlzheimer’sdiseaseinclinicaltrials.Am J Neuro-degen Dis.2012;1:205-216.

5.BernickC,CummingsJ,RamanR,SunX,AisenP.AgeandrateofcognitivedeclineinAlzheimerdisease:implica-tions for clinical trials. Arch Neurol. 2012;69:901-905.

6.SabbaghJJ,KinneyJW,CummingsJL.AnimalsystemsinthedevelopmentoftreatmentsforAlzheimer’sdisease:challenges, methods, and implications. Neurobiol Aging. 2013;34:169-183.

7.ApplebyB,NacopoulosD,MilanoN,ZhongK,CummingsJ.Areview:treatmentofAlzheimer’sdiseasediscoveredin repurposed agents. Dementia Geriatr Cog Disorder. 2013;35:1-22.

8.CummingsJL,BanksS,GaryR,KinneyJ,LombardoJ,WalshR,ZhongK.Alzheimer’sdiseasedrugdevelop-ment: translational neuroscience strategies. CNS Spectr. 2013;18(3):128-138.

Dr. Cummings is Director of Cleveland Clinic Lou Ruvo

Center for Brain Health. His specialty interests include

Alzheimer disease and drug development. He can be reached

at 702.483.6029 or [email protected].

Dr. Zhong is Senior Director for Research at Cleveland Clinic

Lou Ruvo Center for Brain Health. Her specialty interests

include Alzheimer disease, mood disorders and drug develop-

ment. She can be reached at 702.483.6049 or [email protected].

Disclosures

Dr. Cummings has provided consultation to the follow-

ing pharmaceutical or device companies: Abbott, Acadia,

ADAMAS, Anavex, Avanir, Baxter, Bristol-Myers Squibb,

Eisai, Elan, EnVivo, Forest, Genentech, GlaxoSmithKline,

Lilly, Medtronic, Merck, Neuronix, Novartis, Otsuka, Pfizer,

Prana, QR, Sanofi, Sonexa, Takeda and Toyama.

Dr. Zhong has provided consultation to the following phar-

maceutical or device companies: Baxter, Janssen and Pfizer.

Figure 3. Organization of the LRCBH clinical trials program according to the mechanism of action targeted.

Amyloid disease-modifying

• Bexarotene

• Immunotherapy

• BACE inhibitor

non-amyloid disease-modifying

• Resveratrol

• Pioglitazone

Symptomatic

• Dextromethorphan/quinidine

• Transcranial magnetic stimulation

• Axona®


P S y C H o - o n C o l o G y

Recognizing the significant mental health needs of

oncologypatients,theNationalInstitutesofHealthand

theInstituteofMedicine(IOM)assembledamultidisci-

plinary committee to investigate barriers to psychosocial

healthcare in ambulatory oncology centers. The com-

mittee’sfindingswerepublishedina2007IOMreport,

Cancer Care for the Whole Patient: Meeting Psychosocial

Needs,1 which outlined a new standard that integrates

psychosocial health services into cancer care. Part of this

new standard calls for routine psychosocial “distress”

screeningofoncologypatients(figure1).TheAmerican

College of Surgeons Commission on Cancer has adopted

theIOMrecommendations,addingevaluationofdistress

asarequisiteforaccreditationeffectivein2015.

Some studies suggest that patients tend not to disclose

their psychological concerns to their medical providers

and that depression and anxiety are underrecognized and

undertreated in oncology settings. Systematic screening,

however, encourages early identification of and interven-

tion for at-risk individuals, offering the opportunity to

mitigate the emotional burden and medical care-related

costs resulting from mental health problems.

Making Screening Systematic

Challenges to the implementation of screening include

enabling easy completion by patients and delivering

clinically relevant results to providers in a rapid, acces-

siblemanner.Asmorehealthcaresystemsincorporate

electronic medical records (EMRs), integrating screening

data into the chart is critical.

Ourpsychosocialoncologyprogramhasdeveloped

ascreeningsystemthatusesauniqueCleveland

Cleveland-designed tool called the Knowledge Program.

The Knowledge Program immediately imports screen-

Distress Screening: A Call to Action

The prevalence of depression is markedly higher in

theoncologypopulation,at25percent,comparedwith

the general population, where lifetime prevalence is

16percent.Ratesofanxietyarenotablyhigheraswell,

particularly in patients with advanced cancer. These

psychiatric disorders directly impact medical care and

may result in prolonged hospitalizations, delays in

starting treatment, reduced adherence to therapy, lower

pain tolerance and a tendency to receive more aggressive

therapies at the end of life. Moreover, individuals with

cancer are three times more likely to commit suicide

than the general population, with poor cancer prognosis

conferring greater risk.

Psycho-oncology update: Innovating an Approach to Systematic Distress Screening in Patients with Cancer

By Beth Gardini Dixon, PsyD, and Isabel Schuermeyer, MD

KEy PointS

Beginning in 2015, routine psychosocial distress screening of oncology patients will be a requisite for accreditation by the American College of Surgeons Commission on Cancer.

Cleveland Clinic’s psychosocial oncology program has developed a screening system that uses an eMR-integrated screening tool to assess patients for psy-chosocial distress, enabling providers to view results at the time of patient visits.

use of this eMR-integrated screening tool has enabled us to gauge whether we are meeting program goals and has guided our selection of screening instruments.

Systematic screening for psychosocial distress in oncol-ogy patients helps uphold standards in care quality and facilitate optimal patient outcomes.

Receiving a cancer diagnosis is a significant stressor for even the most resilient individuals. Factors such as disease

severity, complex treatment regimens and uncertainty about prognosis can magnify distress for patients and their

families. Research has demonstrated that a cancer diagnosis increases the risk for depression, anxiety and reduced

quality of life. not only are these risks present during active oncology treatment, but emerging literature on survivor-

ship suggests that distress may persist beyond the period of active care. new standards in oncology prioritize emo-

tional well-being as a key aspect of treatment, and Cleveland Clinic’s taussig Cancer institute, in collaboration with

the Center for Behavioral Health, is responding with innovative screening strategies.


P S y C H o - o n C o l o G y

ing results into the EMR. Patients

complete the screening tool on a

tablet computer when checking in for

appointments. Screening informa-

tion is then transferred electronically

into the EMR so that the provider has

the immediate results prior to seeing

the patient. This system allows for

intervention during the appointment

and helps guide referrals to specific

services.

letting Data Drive improvements

Anotherdistinctivefeatureofthe

Knowledge Program-based screen-

ing method involves compilation of

results into a database for analysis.

Data may be sorted according to

multiple variables, such as demo-

graphics, disease type and test

scores. Comparing aggregate data

to expected patterns based on the

published literature has enabled us

to gauge whether we are meeting the

program goals.

During our pilot phase of screening

implementation, this data analysis

capability highlighted limitations of the trial screening

instrument we were using, which appeared to under-

estimate clinically significant distress levels in our

outpatient oncology population. For instance, this instru-

mentfoundonly9percentofpatientsinthefirstquarter

of2013tohavemoderateorhighlevelsofdistress,which

is markedly lower than the expected rate of approxi-

mately35percent.Thesefindingspromptedustorevise

our selection of screening instruments.

ongoing need Calls for a Systems Solution

Psychosocial healthcare needs to be addressed through-

out the continuum of cancer care. Systematically

monitoring and tracking distress — as one element of a

comprehensive psychosocial health services program —

servestoupholdnewqualitystandardsinoncologyand

facilitate optimal treatment outcomes. n

RefeReNCe

1.InstituteofMedicine. Cancer Care for the Whole Patient: Meeting Psychosocial Needs. Washington, D.C.: The NationalAcademiesPress;2007.

Dr. Dixon is a staff clinical psychologist in the Psycho-Oncol-

ogy Program in Cleveland Clinic’s Taussig Cancer Institute.

She can be reached at 216.442.5229 or [email protected].

Dr. Schuermeyer is Director of Psycho-Oncology and a staff

psychiatrist in Cleveland Clinic’s Center for Behavioral

Health and the Department of Psychiatry and Psychology.

She can be reached at 216.444.5965 or [email protected].

The authors wish to acknowledge the Psycho-Oncology

Program social workers and the Knowledge Program team

for their contributions to the work reported here.

Standard of Psychosocial Care

facilitate effective communication between:

Patient/family

team

Provider

Identify patient/family psychosocial needs

Design and implement plan

follow up, re-evaluate and adjust plan

Coordinate biomedical and psychosocial care

engage patient/family in the management of illness

Link patient/family to services

Figure 1. Model for psychosocial services in oncology. Adapted

from the Institute of Medicine.1


Making Sense of the Brain’s Weak Magnetic Fields

UnlikefunctionalMRI,whichusesstrongmagnetic

fields, MEG instead measures the extraordinarily weak

magnetic fields generated by brain functions. Using no

radiation or magnetic fields, sensors in a helmet (gradi-

ometersand/ormagnetometers)pickupthemagnetic

fields generated by the brain’s electrochemical activity.

Becausethegeneratedmagneticfieldisquitesmall,

about 1 billion times smaller than the earth’s magnetic

field,itsacquisitionrequiresspecializedelectronicsand

a magnetically shielded room.

MEG offers advantages over electroencephalography

(eeG)inthatitprovidesforeasyacquisitionofvery-high-

density(approximately100-300channels)wideband(DC

–2000Hz)recordingsofcurrentswithinthebrainand

with high dynamic range. Magnetic fields, in contrast to

scalp potentials, suffer minimal attenuation and distor-

tion from the various tissues that the electrical currents

have to cross to reach the scalp surface. Whereas more

frequentlyusedfunctionalimagingmodalities(fMRI,

SPECT and PET) have poor temporal resolution, MEG

records activity in real time with excellent temporal reso-

lution (< 1 ms). Single focal sources can be localized with

goodresolution(1-5mm).

How MEG is used

MeGisfrequentlyusedtohelplocalizeseizuresin

patients with intractable epilepsy as well as to examine

neurophysiological responses (evoked magnetic fields)

tovisual,auditoryandtactilestimuli.AfteraMeGstudy

has been obtained, the information is processed to allow

determination of dipoles that indicate the area in which

the activity (or the highest amount of activity) is occur-

ring. The analyst uses coregistration software to localize

thedipoleonthepatient’sMRI.Theresultisanimage

that identifies the areas (in the case of epilepsy) where

spikes or asynchronous activity were observed during

MeGacquisition(figure1).

The MEG lab at Cleveland Clinic has obtained MEG studies

fromalmost700patientssinceitsinceptionin2008.Our

ongoing research involving MEG is examining language

lateralization, the use of MEG with neurosurgical mapping

techniquestohelplocalizeepileptogeniczonesinpatients

with medically intractable epilepsy, and the development

of algorithms to improve the information obtained.

neurophysiological Responses to Stimuli

Inthecaseofneurophysiologicalresponsestostimuli,

many studies have examined the median nerve response

to electrical stimulation. This research has determined

that different patient populations may respond more

slowly than control subjects due to changes in conduc-

tivitycausedbythediseaseprocess.Otherstudieshave

determined that age is a significant mediating factor to

beconsideredwhenanalyzingMeGresults.Otherfactors

to consider when using MEG include medications the

subject is taking and, in some cases, the subject’s height,

Magnetoencephalography Provides new Window into Brain Connectivity Across Diverse neuropsychiatric Conditions

By Patricia Klaas, PhD, and John C. Mosher, PhD

F u n C t i o n A l i M A G i n G i n n E u R o P S y C H i A t R y

KEy PointS

Meg enables examination of changes in brain activ-ity with greater temporal and spatial resolution than is possible with traditional brain-mapping and imaging modalities.

Meg is increasingly being used in research examining brain connectivity in diverse disease states ranging from depression to schizophrenia to autism.

Cleveland Clinic has one of the most clinically prolific Meg laboratories in the united States and is pursuing research with Meg in multiple applications.

Magnetoencephalography (MEG) is useful in a number of patient populations to identify pathways of connectivity

in the brain so that we can better understand why things go wrong when they go wrong. Cleveland Clinic has one

of the most clinically prolific MEG laboratories in the United States and is researching MEG’s use for a number of

applications. this article reviews MEG’s emerging utility for examining brain connectivity across various neuro-

psychiatric conditions.


F u n C t i o n A l i M A G i n G i n n E u R o P S y C H i A t R y

as taller individuals have longer latencies to median

nerve stimulation due to the necessarily longer path to

thecortex.figure2depictsthemediannerveresponse,

as determined by MEG after processing of the evoked

magneticfield,inthepre-andpostcentralcortexat36

ms. Patients with intractable epilepsy show a great deal

of variability in their response to this stimulation.

Psychiatric Applications

OtherresearchhasusedMeGtoassesspre-attentive

dysfunction in bipolar disorder and has determined

that at the pre-attentive level, information processing is

impaired in patients with bipolar disorder.1 MEG also

enables analysis of temporal correlations or coherence

within a number of populations. Clinical research has

examined neural coherence in dementia and band-

width differences in patients with schizophrenia, and

other studies have sought to develop a neural marker in

patients with depression to help distinguish them from

patients with bipolar disorder. Patients with autism

have been studied to determine whether MEG can help

identify a neural marker2 or if differences exist in connec-

tivity. Studies in connectivity, like the one conducted by

Hinkley et al, have examined the role of corpus callosum

development “in integrating information and mediating

complex behaviors.”3

MeGisanextremelyusefultechniquethatisbeingused

morefrequentlyinresearchexaminingbrainconnectiv-

ityinpopulationswithdepression,Alzheimerdisease,

Parkinson disease, schizophrenia, leukemia, multiple

sclerosisandmanyotherdiseases.Itshightemporaland

spatial resolution allows for examination of changes in

brainactivitywithgreatertemporalresolutionthanfMRI

and greater spatial resolution than EEG. n

RefeReNCeS

1.TakeiY,KumanoS,MakiY,etal.Preattentivedysfunc-tion in bipolar disorder: a MEG study using auditory mismatch negativity. Prog Neuropsychopharmacol Biol Psychiatry.2010;34:903-912.

2.WilliamsMA,SachdevPS.Magnetoencephalographyinneuropsychiatry: ready for application? Curr Opin Psychiatry.2010;23:273-277.

3.HinkleyLBN,MarcoeJ,findlayAM,etal.Theroleofcorpus callosum development in functional connectivity and cognitive processing. PLoS One.2012;7(8):e39804.

Dr. Klaas is an associate staff member in Cleveland Clinic’s

Center for Behavioral Health and Department of Psychiatry

and Psychology. She also has appointments in Cleveland

Clinic Lou Ruvo Center for Brain Health, the Epilepsy

Center and the Department of Neurosciences. Her specialty

interests include epilepsy, magnetoencephalography, neu-

ropsychology and behavior research. She can be reached at


Dr. Mosher is a staff member in Cleveland Clinic’s Epilepsy

Center whose specialty interests include magnetoen-

cephalography. He can be contacted at 216.444.3379 or

[email protected].

Figure 1. MEG-enabled dipole localization on MRI demonstrating epileptogenicity (yellow markers).

Figure 2. Activity in the pre- and postcentral cortex, as determined by MEG after processing of the evoked magnetic field, following median nerve stimulation.


Abstinence-Based Models: the Acute Approach

Most abstinence-based approaches to opiate dependence

presume that patients should enter into residential treat-

ment, where they will be weaned off narcotics during the

“detox” phase of treatment and then spend a few more

weeks in a rehabilitation program. Such programs typi-

callyembracea12-step-basedapproachtoaddressingthe

issues underlying the patient’s addiction.

Abstinence-basedaddictionrehabilitationcenters

abound in the United States and remain the predomi-

nant modality of treatment despite taking an acute-care

approach to what is well recognized as a chronic disease.

Patients who enter such programs are expected to go

away to treatment (usually outside their geographic area)

for approximately four weeks and then return home,

freeofdrugsanddeemed“inrecovery.”Ifsuchapatient

subsequentlyhasanyexacerbationofhisorherchronic

disease that leads to use of drugs — even on a single occa-

sion — the patient is considered a “treatment failure.”

traditional MAt Programs: Effective but impractical

MATprogramsthatusemethadoneastheirmaintenance

medicationarerequiredtobefederallylicensed.federal

restrictions on methadone programs limit their avail-

ability, and most moderately sized metropolitan areas

have only one or two such programs. Patients in these

programs must initially go to the methadone clinic every

day to receive their dose of medication, which presents a

major inconvenience if they have transportation issues or

are trying to reintegrate into the workforce. Many, if not

most, of these clinics are located in crime-afflicted areas,

and savvy drug dealers often loiter around the clinics to

entice patients to abandon recovery and buy their illicit

drugs.Itisnosurprisethat,despitemethadoneclinics’

A D D i C t i o n M E D i C i n E

proven efficacy, it is difficult to sell patients on the idea

of engaging in long-term treatment at these clinics.

MATprogramsthatuseSuboxoneasamaintenance

medication are typically run out of outpatient physician

offices — often in primary care settings, where Suboxone

is provided as a service to opiate-dependent patients by

doctorswhoarenotaddictionologists.AlthoughSuboxone

programs are typically not managed by addiction special-

ists, it is hard to argue with their effectiveness, which

closely parallels that seen with methadone maintenance.

A nontraditional Evidence-Based Approach that Works

ClevelandClinic’sADRChasbeeninexistencefornearly

30yearsandhasarichhistoryoftakingevidence-based

approaches to address the complex issues often inherent

in the treatment of patients suffering from addiction.

OuroutcomeswithSuboxonehaveconsistentlyexceeded

those reported with traditional office-based programs.

For instance, prospective follow-up data from patients

startedonSuboxoneinApril2012thatlookedatnegative

urine drug screens and treatment retention at three and

sixmonthsshowedthatpatientstreatedattheADRChad

outcomes superior to those reported in the literature by

other respected programs2 (Figure 1).

Combined Approach Drives Success

Ourprogram’ssuccessisdrivenbyacombinedapproach

to treatment: We are neither a traditional residential

program nor a typical office-based provider of Suboxone.

We provide inpatient services for those in need of detoxi-

fication,primarilyfromalcoholand/orbenzodiazepines.

Patients who have undergone detoxification or are start-

ing Suboxone typically begin the next phase of treatment

in our partial hospitalization program (PHP), where they

Medication-Assisted treatment with Suboxone: finding Success with a nontraditional Approach to opiate Dependence

By Jason M. Jerry, MD

opiate dependence is a chronic relapsing and remitting illness — few experts will argue this fact. the body of evi-

dence shows that chronic approaches to opiate dependence, such as medication-assisted treatment (MAt) with either

methadone or Suboxone® (buprenorphine-naloxone), are superior to acute-care models that involve detoxification and

residential treatment.1 Yet the addiction treatment field has long been polarized over whether to pursue abstinence-

based approaches or MAt. At Cleveland Clinic’s Alcohol and Drug Recovery Center (ADRC), we believe a fresh

approach to this question is long overdue. A “one size fits all” strategy cannot be employed in real-world clinical set-

tings to effect long-lasting change.


A D D i C t i o n M E D i C i n E

engagein12-step-basedtreatmentfivedaysaweek.On

completion of the PHP, patients transition into one of

three intensive outpatient programs.

Close monitoring of patients, especially during the criti-

calfirst90days,alsocontributestoimprovedoutcomes.

Patientsarerequiredtoprovideweeklyurinesamples

and are given only one-week prescriptions for Suboxone

throughout their first three months in treatment. Patients

who struggle in treatment are typically moved to a higher

level of care that may involve staying at a local halfway

house if they wish to continue in our program.

Ourprogramsarestaffedbythreeboard-certifiedpsychi-

atrists who are certified medical review officers and also

board-certified in either addiction medicine or addiction

psychiatry. Such heavy staffing in psychiatry allows us to

attend to the psychiatric comorbidities that so commonly

plague those suffering from addictive disorders.

AttheADRC,weprideourselvesondevelopingtreatment

plans for our patients that are consistent with the

evidence base yet tailored to patients’ idiosyncrasies.

The validity of our approach is evidenced by our

outcomes measures, the fact that our program has

thrivedfornearly30years,andthestrongsupportof

alumni who volunteer their time to help those just

entering treatment. n

RefeReNCeS

1.JerryJM,CollinsGB.Medication-assistedtreatmentofopiate dependence is gaining favor. Cleve Clin J Med. 2013;80:345-349.

2.SoeffingJM,MartinDL,fingerhoodMI,etal.Buprenor-phine maintenance treatment in a primary care setting: outcomes at 1 year. J Subst Abuse Treat.2009;37:426-430.

Dr. Jerry is a staff psychiatrist in Cleveland Clinic’s Alcohol

and Drug Recovery Center and Clinical Assistant Professor

of Medicine, Cleveland Clinic Lerner College of Medicine.

His specialty interests include drug and alcohol addiction,

with a focus on novel substances of abuse including synthet-

ic legal intoxicating drugs (“bath salts,” “spice/K2,” phenaz-

epam, etc.). He also works with professional athletes and is

an approved provider for the NBA-NBA Players Association

Anti-Drug Program. He can be reached at 216.363.2357 or

[email protected].

KEy PointS

evidence shows that chronic approaches to opiate dependence are superior to acute-care models, but debate surrounds whether to pursue abstinence-based approaches or medication-assisted treatment (MAt).

Abstinence-based models are limited by taking an acute-care approach to a chronic disease, while tradi-tional MAt programs can be impractical to run or often are not managed by addictionologists.

using a combined approach that draws on elements of Suboxone-based MAt and inpatient services, Cleveland Clinic’s Alcohol and Drug Recovery Center achieves patient outcomes that consistently exceed those reported with office-based MAT.

Neg

ativ

e ur

ine

drug

scr

eens

(%

)

0

20

40

60

80

100

Negative Urine Drug Screen RateDuring First Six Months of Treatment

84

70

Cleveland ClinicADRC

(N = 87)

Soeffinget al2

Figure 1. Rates of negative urine drug screens among participants in Cleveland Clinic’s Alcohol and Drug Recovery Center (ADRC) compare favorably with some of the best rates reported in the literature.


B R A i n S t i M u l A t i o n i n n E u R o P S y C H i A t R i C D i S E A S E B R A i n S t i M u l A t i o n i n n E u R o P S y C H i A t R i C D i S E A S E

Development of Innovative technologies for Brain Stimulation: going Microscopic to overcome earlier Limitations

By John T. Gale, PhD

Despite the success of these technologies, a few techni-

cal and practical limitations have impeded our ability to

take advantage of their full potential. To overcome these

limitations, researchers in Cleveland Clinic’s Department

ofNeurosciences,inassociationwiththeDepartment

of Psychiatry and Psychology, are evaluating a new brain

stimulation technology called microscopic magnetic stim-

ulation(µMS).Ourfindingsthusfarprovidearationalefor

further exploration of µMS as a prospective therapeutic

tool with both preclinical and clinical applications.

Microscopic Magnetic Stimulation: How it Works

This new µMS technology involves the use of millimeter-

to submillimeter-sized coils (Figure 1, left), which avoid

the metal contact needed to modulate brain activity with

electricalstimulationmodalities.Incontrasttothecoils

used in TMS, µMS coils’ small size allows them to be

implanted directly into the brain or in close proximity to

thebrainsurface.Onceimplanted,coilscanbesupplied

with electrical current via implanted impulse genera-

tors, similar to those used for cardiac pacemakers. When

current is applied to a coil, a magnetic field is generated

around the coil (Figure 1, right) that penetrates into the

tissue.Asthemagneticfieldspreads,itcausesachange

in electrical charge around the brain tissue that can

make brain cells change their activities.

induction Coil is not in Contact with Brain tissue

OneofthepotentialusesofµMSistoimprovedelivery

of stimulation to the brain. The principal problem with

standardtechniquessuchasdeepbrainstimulation(DBS)

is that the metal stimulation conductor comes into direct

contact with brain tissue. This interface induces a neuro-

inflammatory response and promotes scarring at the

electrode contacts, which can affect charge densities at the

stimulation site and possibly reduce therapeutic efficacy.

Onewaytoovercomethereductioninchargedensitiesis

simply to increase the amplitude of stimulation.2 However,

increasing stimulation amplitudes might result in

inadvertent activation of surrounding structures, which

can lead to stimulation side effects. Two such side effects

are paresthesias and diplopia, secondary to inadvertent

activation of the medial lemniscus and corticobulbar

fibers, respectively.3

Inadditiontothesepotentialinflammatorycomplica-

tions,performingMRIproceduresonpatientswith

implanted DBS leads calls for specific precautions.

Reports indicate that heating of the leads may cause

tissuedamage.Asisthecasewithinflammatorypro-

cesses, heating occurs as a result of the direct interface

between the stimulation contact and the brain tissue.

Specifically, the cabling of the DBS lead can absorb

radiofrequencyenergyproducedbytheMRIscanner

and transfer this energy (in the form of heat) to the

brain at the site of the leads.4,5

Electrical stimulation and transcranial magnetic stimulation (TMS) have proved to be beneficial for patients with certain

neurologic disorders, including Parkinson disease, essential tremor and dystonia. these treatments are also being ex-

plored as a surgical option for patients with neuropsychiatric conditions such as major depression and obsessive-com-

pulsive disorder.1

KEy PointS

Current brain stimulation modalities present possible surgical options for neuropsychiatric conditions such as major depression and obsessive-compulsive disorder, but technical and practical limitations impede their use at full potential.

A new brain stimulation technology called microscopic magnetic stimulation (µMS) overcomes many of these limitations through use of tiny coils that do not directly contact brain tissue.

Our research group was the first to demonstrate that µMS is capable of activating neuronal circuitry on the systems level, which is an important step toward clini-cal use.


B R A i n S t i M u l A t i o n i n n E u R o P S y C H i A t R i C D i S E A S E

Incontrast,µMSovercomestheselimitationsbykeeping

the induction coil out of direct contact with the target

tissue. The coil can be enclosed in a biocompatible

coating (such as parylene), which mitigates both the

inflammatoryprocessesandpotentialMRIhazards.In

addition, due to inherent properties of magnetic field

spread, it may be possible to shape the spread of the neu-

ronal activation field to prevent unintended activation of

adjacent brain structures, thus limiting side effects.

tiny Size Allows for implant Flexibility

Althoughdirectelectricalstimulation(stimulationofthe

brain through the scalp) and TMS offer advantages over

invasive technologies, they have limited applications.

Specifically,bothtechnologiesrequireprecisecontact

placement in order to modulate specific brain regions.

Therefore, highly trained personnel are needed to ensure

that contacts are appropriately positioned to maximize

outcomes.Inaddition,TMSrequireslargepowersources

to drive the magnetic fields because the coils are large

andsituatedfarfromthestimulatedtissues.Asaresult,

TMStherapyrequiresthatpatientsmakerepeatedoffice

visits to receive treatment. Together, these drawbacks

limit the feasibility of long-term neuroprosthetic applica-

tions, reducing both their efficacy and accessibility.

Incontrast,thesmallsizeofµMScoilsenablesneurosur-

geons to implant them close to (either within or adjacent

to)thespecificbraintargets.Also,theµMSdevicesuse

farlessenergythandotheTMSdevices.Anotherareain

which µMS has proved effective is in activating the local

neural circuitry of the retina in vitro.6

First in Vivo Evidence of trans-Synaptic neuronal Activation

Inourcurrentstudies,wehavedemonstratedthatµMS

technology is capable of activating neuronal circuitry on

the systems level with use of an in vivo rodent prepara-

tion. Specifically, µMS of the dorsal cochlear nucleus

activatesneuronsoftheinferiorcolliculus(figure2,

top).Additionally,wehavedemonstratedtheefficacyand

characteristics of trans-synaptic activation using differ-

ent amplitudes of stimulation, where higher amplitudes

reduce latencies and decrease variability. These findings

represent an important step toward clinical use, as they

are the first to demonstrate that µMS is capable of trans-

synaptic neuronal activation in vivo.

Computer Simulations of µMS

Inadditionalstudies,weareexaminingandoptimizing

the design of µMS technologies using computer simula-

tions(figure2,bottom).Thesesimulationsallowusto

Figure 1. (Left) Depiction of the size of a µMS coil relative to that of an overlaid human hair. The dimensions of the microcoils illustrated are 1160 × 1120 × 860 µm (0603LS-103XJLB; Coilcraft Inc.; Cary, Ill.). (Right) Schematic of magnetic fields generated by application of electric current to a magnetic coil.


B R A i n S t i M u l A t i o n i n n E u R o P S y C H i A t R i C D i S E A S E

predict how different designs of µMS technologies will

function prior to their manufacture. This enables us to

design µMS coils with particular shape and size speci-

fications and then test these designs using a computer,

thereby allowing us to commit resources to only the most

promising designs.

other Applications

While this article is focused on the possibility of µMS as

an alternative to DBS, µMS may be useful for a number

of other applications — such as in cochlear, visual and

muscular prosthetic contexts — although these possibili-

ties remain to be tested. We look forward to contributing

to such investigations, as well as to exploring the use of

µMS as a potential tool for investigating the mechanisms

thatunderlieelectricaland/ortranscranialmagnetic

stimulation.7 n

RefeReNCeS

1. BourneSK,eckhardtCA,ShethSA,eskandareN.Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits. Front Integr Neurosci. 2012;6:29.

2.ButsonCR,MaksCB,McIntyreCC.Sourcesandeffectsof electrode impedance during deep brain stimulation. Clin Neurophysiol.2006;117(2):447-454.

3. StarrPA,ChristineCW,TheodosopoulosPV,etal.Implantationofdeepbrainstimulatorsintothesubthalamic nucleus: technical approach and magnetic resonance imaging-verified lead locations. J Neurosurg. 2002;97(2):370-387.

4. AngeloneLM,PotthastA,Segonnef,etal.MetallicelectrodesandleadsinsimultaneouseeG-MRI:specificabsorptionrate(SAR)simulationstudies.Bioelectromag-netics.2004;25(4):285-295.

5. RezaiAR,PhillipsM,BakerKB,etal.Neurostimulationsystem used for deep brain stimulation (DBS): MR safety issues and implications of failing to follow safety recommendations. Invest Radiol. 2004;39(5):300-303.

6.BonmassarG,LeeSW,freemanDK,PolasekM,friedSI,GaleJT.Microscopicmagneticstimulationofneuraltissue. Nat Commun. 2012;3:921.

7. MuggletonN,WalshV.Smallermagnetsforsmarterminds? Trends Cogn Sci.2012;16(9):452-453.

Dr. Gale is an assistant staff member in Cleveland Clinic’s

Center for Neurological Restoration and Department

of Neurosciences. He can be reached at 216.444.9097 or

[email protected].

Figure 2. (Top) Plot of evoked neuronal response to µMS. The plot illustrates overlaid electrophysiologic activity from the inferior colliculus in response to 240 magnetic pulses delivered in the vicinity of the dorsal cochlear nucleus. As shown here, the pulses generated a highly stereotypic artifact (t = 0) and a robust multi-unit response (t = 7 ms). The microcoils used were 21-turn inductors measur-ing 400 × 400 × 600 µm (ELJ-RFR10JFB; Panasonic Electronic Devices Corp. of America; Knoxville, Tenn.). (Bottom) Computer simulation of magnetically induced electrical fields generated during µMS stimulation pulse.


i n t E n S i V E o u t P A t i E n t t H E R A P y

integrated Skills Approach

We employ an integrated skill-building strategy that

uses cognitive behavioral and dialectical behavioral

approaches to develop the following skills:

• Strategiesforchangingthoughts,feelingsandbehaviors

• Mindfulness

• Copingcapacities

• emotionalregulation

• Realityacceptance

• Crisiscoping

• Interpersonalcommunication

PatientengagementisacornerstoneofourIOPapproach.

Afteraninitialcomprehensivepsychosocialassessment

to determine the patient’s personal goals, we engage the

patient in an ongoing collaborative treatment planning

process. Patient feedback is solicited every day on the

benefit of skills taught, the practical application of skills

to daily living, perceived progress toward goals and any

additional patient needs.

Swift Access, open-Ended Aftercare

AlthoughIOPserviceshavebeenavailableatCleveland

Clinic for more than two decades, we have made it a point

to evolve the program according to patient needs, new

evidence and emerging best practices. Recent changes

thatdistinguishourIOPinclude:

• Dedicationofanindependentlylicensedprofessional

counselor whose exclusive role is to provide liaison

serviceforassessmentofreferralstotheIOP.Theresult

is same-day or next-day access to assessment and admis-

sion for most patients.

• AdditionoftheIOPtoourpsychiatryresidents’rotations

to enhance these trainees’ exposure to management

issuesrelevanttotheIOPanditspatientpopulation.

This finding is from the first five months of outcomes

trackingfortheIOP—comprehensivedatacollection

that was made possible by recent standardization of

treatment and processes across all locations where the

IOPisavailableintheClevelandClinichealthsystem.

ioP at a Glance

TheIOP,whichisoperatedbyClevelandClinic’sCenter

for Behavioral Health, is designed to treat adults with

mood or anxiety disorders in a group therapy setting.

Appropriatepatientsarethosewhoarecapableoffunc-

tioning in their daily lives but who stand to benefit from

more concentrated services than those available from

weekly therapy sessions.

The program is offered three or four days a week and

requiresattendanceingrouptherapyforthreeandahalf

hourseachday.Atreatmentcoursegenerallylastsfour

to six weeks but may be shortened or extended based on

patients’ individual needs and assessment results. Group

sizegenerallyrangesfromeightto12patients.

Program goals include helping patients (1) reduce

moodandanxietydisordersymptoms,(2)regainlost

confidence and (3) achieve greater levels of functioning,

such as returning to work, resuming daily activities and

becoming a contributing member of their family.

The program is run by licensed independent social

workers, counselors and psychiatric nurses in consulta-

tionwithastaffpsychologist.frequentcommunications

with referring providers, including regular patient prog-

ress reports, are a program priority and recognized as

essential to long-term patient success.

outcomes Collection effort Showcases value of an evolving Intensive outpatient Program

By Daniel Jones, PhD

Recent participants in Cleveland Clinic’s intensive outpatient program (ioP) for mood and anxiety disorders demon-

strated an average improvement of more than 2.5 points on the 7-point Clinical Global impression Severity of illness

Scale (CGi).


P S y C H i A t R y E D u C A t i o ni n t E n S i V E o u t P A t i E n t t H E R A P y

• Provisionofanaftercaregroupcomponenttohelp

patients reinforce and maintain changes they adopted

during therapy. Patients are free to attend this compo-

nent for as long as they wish after completion of the core

program;patientstypicallycontinueforapproximately

three months.

The aftercare component is aligned with the “relapse

prevention contract” we have long asked patients to sign

upondischargefromtheIOP.Thiscontractconfirmsthat

patients understand their illness, recognize its signs and

symptoms, and designate a family member they will turn

toforassistanceasneeded.Similarly,theIOPincludesa

family support group to discuss strategies for relapse pre-

vention and improved communication within the family.

initial outcomes tracking, Future Steps

TheseandotherIOPfeatureswerestandardizedacross

ClevelandClinicin2012,whichpromptedtheongoing

collectionofoutcomesdataforallIOPparticipants.

Asillustratedinfigure1,the63participantsinthe

IOPfromlateJulythroughDecember2012experienced

animprovementinmeanCGIscorefrom5.46attheir

initial assessment for the program (indicating markedly

severeillness)to2.80atprogramdischarge(indicating

mild illness).

Wecontinuetoconductpre-andpost-programCGI

assessments and will report participants’ outcomes

on an annual basis moving forward. Cleveland Clinic

recentlyjoinedtheAssociationforAmbulatoryBehavioral

Healthcare and looks forward to opportunities to share

outcomesdataandotherwiseadvanceIOPcareona

national basis through that and other forums. n

Dr. Jones is a psychologist in the Department of Psychiatry

and Psychology and Director of the Intensive Outpatient

Programs in Cleveland Clinic’s Center for Behavioral

Health. His specialty interests include adult psychotherapy

and relational and integrative approaches to psycho-

therapy for depression and anxiety. He can be reached at


KEy PointS

Cleveland Clinic has begun collecting and reporting out-comes of all patients completing its intensive outpatient program (IoP) for comprehensive management of mood and anxiety disorders.

Among the 63 participants in the IOP during the first five months of outcomes collection, mean CGI score improved from 5.46 at initial assessment (indicating markedly severe illness) to 2.80 at discharge from the program (indicating mild illness).

the Cleveland Clinic IoP features open-ended aftergroup care and virtually immediate access through use of a dedicated licensed professional counselor for assess-ment of referrals.

Mea

n C

GI s

core

1

2

3

4

5

6

7

Illness Severity Before and After Intensive Outpatient Program (N = 63)

Initial assessment Follow-up assessment

Figure 1. Mean group CGI score improved from 5.46 (indicating marked illness) at initial assessment for the intensive outpatient program (IOP) to 2.80 (indicating mild illness) at program completion (P < .0001) among 63 IOP participants in the first five months of IOP outcomes tracking. The CGI (Clinical Global Impression Severity of Illness Scale) is a 7-point scale.


P S y C H i A t R y E D u C A t i o n

AllstudentscompletedtheNationalBoardofMedical

examiners(NBMe)psychiatrytestattheendoftheir

four-week psychiatry rotation as an objective and

validated measure. They were also asked to assess their

confidence in their clinical note writing and oral presen-

tation skills as well as their opinions about use of the

EMR in medical education.

Call for a Hybrid template

TherewasnodifferenceinNBMetestscoresbetweenthe

two groups. Students’ subjective comments revealed that

thesmarttemplatewasviewedasenablingquickwriting

of patient notes but that the bare-bones template was

perceived as better suited to learning correct preparation

of medical documentation.

The most striking finding was that students appreciated

the use of pre-populated drop-down menus for learning

clerkship-specific material, particularly the terminology

ofpsychiatry.Overall,studentsexpressedapreferencefor

a hybrid template that utilizes some smart functions but

also allows for creation of free-form text.

Do Documentation templates impact training?

Today’s highly structured “smart” EMR documentation

templates automatically import patient health informa-

tion, utilize hundreds of boilerplate text options and

rely on layers of drop-down menu choices. These smart

templates can improve clinical efficiency, but they de-

emphasizethecreationoffree-formtext.AleadingeMR

system with such documentation templates, Epic, is used

by medical students, residents, fellows and attending

physicians at Cleveland Clinic and elsewhere.

Despite the many merits of these documentation tem-

plates, it was unclear to us whether they are ideally suited

for training medical students to document a thorough

history and exam, prepare a differential diagnosis, and

formulate a comprehensive assessment. These are skills

we believe every student should master by the end of his

or her training. The medical literature provides little

guidance on this topic, so we decided to study it ourselves

among third-year medical students from the Cleveland

Clinic Lerner College of Medicine and Case Western

Reserve University during their psychiatry clerkship at

Cleveland Clinic.

test of two templates

ThestudyranfromOctober2011throughDecember

2012andcomparedahighlystructuredsmarttemplate,

whichdidnotrequiremuchdenovoinformationentry,

with a bare-bones template that included only standing

headings (such as chief complaint, history of present

illness,pastmedicalhistory,etc.)andrequiredmuch

more information entry. Sixty-two medical students were

randomized to use either the bare-bones template or the

smart template for each new patient they saw during their

two-week consultation-liaison psychiatry rotation.

Medical Students and the eMR: Improving the educational experience by tailoring templates

By Margo C. Funk, MD

use of the electronic medical record (EMR) is fast becoming standard practice, yet medical students typically do not

have the option of using an EMR documentation template that has been tailored for their training. Within Cleveland

Clinic’s Section of Consultation-liaison Psychiatry, we have developed a documentation template that helps medical

students learn psychiatric content and terminology while still fostering independent and critical thinking.

It was unclear whether standard

templates were well suited to train

students to document a thorough

history and exam, prepare a differ-

ential diagnosis, and formulate a

comprehensive assessment.



Figure 1. Examples of the hybrid documentation template we’ve developed with detailed drop-down menus as well as areas for free-form text, which are indicated by strings of asterisks (***). Panel A shows the “psychiatric review of systems” menu for depression. Panel B shows the same menu for post-traumatic stress disorder, here highlighting a second level of drop-down menu if the student chooses “re-experiencing of trauma.” Panels A and B both highlight the expectation that the student manually creates text for “chief complaint,” “history of present illness (HPI),” “past psychiatric history,” etc. These sections are not auto-populated with information saved in the chart. Panel C shows a nearly completed mental status exam, highlighting use of a drop-down menu for “thought process.”


A

B

C


the EMR as a teaching tool

This study suggests that the EMR documentation

template has strong potential for use as a teach-

ing tool. To provide our medical students with the

richest educational opportunity, we in the Section

of Consultation-Liaison Psychiatry have developed a

template specifically for medical student use (Figure

1). Much of it consists of headings and subheadings,

but drop-down menus are provided in areas where

we believe students would benefit from exposure to

more psychiatry-specific content, particularly in the

psychiatric review of systems and the mental status

examination. Rather than viewing drop-down menu

choices as shortcuts, students find them useful as a way

to learn more content and consider all relevant pos-

sibilities when describing psychiatric symptoms and a

patient’s mental status.

Different needs at Different Stages of training

Unlike residents and attending physicians, medical

students are at the beginning of their medical training

and are focused primarily on learning a core set of

skills.Incontrast,residentshavealreadylearnedcore

content and are adjusting to medical practice and effi-

ciency.Itfollowsthatthesegroupshavedifferentneeds

when preparing a medical record and that the template

they use should reflect those differences.

The findings from our psychiatry service are likely

to be relevant for other departments and specialties.

Establishing an EMR template tailored to medical stu-

dents for every service in a hospital would provide an ideal

teachingopportunity,althoughitwouldofcourserequire

effort from educators and clerkship directors. But the

eMRisheretostay,andIchallengemycolleaguesinpsy-

chiatry and other disciplines to consider how a medical

student-tailored documentation template might fit into

theireMRsystems.Ourstudyconfirmsthatinclusionof

such a template is worth the effort in terms of enhancing

preparation of the next generation of physicians. n

Dr. Funk is a consultation-liaison psychiatrist in Cleveland

Clinic’s Center for Behavioral Health, Assistant Professor of

Medicine in the Cleveland Clinic Lerner College of Medi-

cine (CCLCM), Discipline Leader for the CCLCM Psychiatry

Clerkship and Associate Training Director for the Adult

Psychiatry Residency Program. Her specialty interests

include psychiatric management of patients with cardiac

illness, trauma-related disorders, and medical student and

resident education. She can be reached at 216.444.5425 or

[email protected].


The EMR is here to stay, so I chal-

lenge my colleagues to consider

how a medical student-tailored

documentation template might fit

into their EMR systems. Our study

confirms that it is worth the effort.

KEy PointS

Although use of the eMR and ”smart” documentation templates are quickly becoming standard practice, templates tailored to the needs of medical students are generally not available.

our study among medical students during their psychia-try clerkship found that they believe they’d learn best from a hybrid documentation template that includes drop-down menus and areas for free-form text.

Student-tailored eMR documentation templates should be considered for all hospital departments responsible for instructing medical students.


early Intensive Behavioral Intervention for Autism Spectrum Disorders Maximizes Mainstream educational Placements

By Thomas W. Frazier II, PhD

the Early Childhood Program within Cleveland Clinic Children’s Center for Autism provides intensive applied behavior

analysis services to children 18 months to 6 years old. these services allow a majority of children who exit the

program to transition to a less intensive educational placement.

The Early Childhood Program, which is also part of the

ClevelandClinicLernerSchoolforAutismforschool-age

children, provides early, intensive behavioral interven-

tion year-round to young children who are diagnosed

withautismspectrumdisorders.Childrenreceive30or

more hours per week of intervention through part-

nership between the education team and the child’s

parents/guardians.

Utilizing the science of applied behavior analysis

and child development principles, an individualized

curriculum is designed to teach communication,

social interaction, play, and a range of functional

and adaptive skills.

improving Mainstream Placements

Sincetheprogramopenedin2002,101studentshave

graduated. The majority of children who have exited

the Early Childhood Program over the past decade have

moved on to mainstream placements with minimal or

no educational supports needed (39 percent) or to less

intensivespecialeducationplacements(26percent)that

donotrequireintensivebehavioralintervention(figure

1).Aminorityofstudents(35percent)continuetoneed

intensive behavioral intervention.

Asacomparison,previousstudiesofintensivebehavioral

intervention programs for preschoolers have found rates of

minimal-supportplacementsofapproximately30percent.

KEy PointS

outcomes from the Center for Autism’s early Childhood Program indicate that young children with autism who attend the program experience substantial improve-ments in their ability to function independently in their future educational placements.

Over the past five years, an increasing percentage of preschoolers have exited to less intensive placements where intensive behavioral intervention is no longer required for student success.

Better language at program entry and larger gains in language early in treatment nearly perfectly predicted more favorable placement at exit.

A student in the Early Childhood Program works 1-to-1 with a behavior therapist during a group art project. Each student works on individual-ized goals that are developed based on his or her abilities and needs.

P E D i A t R i C B E H A V i o R A l H E A l t H


Perc

enta

ge o

f pre

scho

ol s

tude

nts

0

5

10

15

20

25

30

35

40

45

Early Childhood Program Placement Outcomes

Minimal educational support

placement

Less intensive educational support

placement

Intensive behavioral intervention placement

39%

26%

35%

Figure 1. Cumulative Early Childhood Program placement outcomes, 2002 to 2012 (N = 101), show that a majority of graduates exited to less intensive educational placements that did not require intensive behavioral intervention.

Perc

enta

ge e

xitin

g to

le

ss in

tens

ive

supp

ort

52

54

56

58

60

62

64

66

Percentage of Students in the Early Childhood Program Exiting to Less Intensive Placement

20122011201020092008

57%58%

61%

64% 64%

Figure 2. A steady increase has been observed in the percentage of Early Childhood Program students who exit to educational placements where intensive behavioral intervention is no longer required for student success.

Overthepastfiveyears,anincreasingpercentageof

preschoolers have exited to settings where intensive

behavioralinterventionisnolongerrequiredforstudent

success(figure2).Theseplacementsincludemainstream

classrooms without any additional support or with either

pullout intervention (e.g., individualized instruction in

mathematics or reading) or an aide providing behavioral

and academic support as necessary. Higher baseline

language scores after six months of intervention nearly

perfectly predicted minimal-support placement at exit.

Early intervention Reduces Costs

These findings indicate that young children with autism

who attend the Early Childhood Program experience

substantial improvements in their ability to function

independently, resulting in decreased resource utiliza-

tion and cost to the public education system. n

SUGGeSTeDReADING

GranpeeshehD,TarboxJ,DixonDR.Appliedbehavioranalytic interventions for children with autism: a descrip-tion and review of treatment research. Ann Clin Psychiatry. 2009;21:162-173.

DawsonG,RogersS,MunsonJ,etal.Randomizedcontrolled trial of an intervention for toddlers with autism: the Early Start Denver Model. Pediatrics.2009;125(1):17-23.

HowlinP,MagiatiI,CharmanT.Systematicreviewofearlyintensive behavior interventions for children with autism. Am J Intellect Dev Disabil.2009;114(1):23-41.

SmithT,BuchGA,GambyTe.Parent-directed,intensiveearly intervention for children with pervasive developmen-tal disorder. Res Dev Disabil.2000;21(4):297-309.

eikesethS,SmithT,Jahre,eledevikS.Intensivebehavioraltreatment at school for 4–7-year-old children with autism: a 1-year comparison controlled study. Behav Modif. 2002;26(1):49-68.

Dr. Frazier is a staff psychologist in Cleveland Clinic Chil-

dren’s Center for Pediatric Behavioral Health and Center

for Autism. His research interests include studies to better

understand autism symptoms and diagnosis, identification

of autism traits in unaffected relatives, and brain imaging

studies of autism. He can be reached at 216.448.6440 or

[email protected].

P E D i A t R i C B E H A V i o R A l H E A l t H


Hearts and Minds: offering Behavioral Health Services in a Cardiology Clinic to Boost Patients’ Spirits — and outcomes

By Leo Pozuelo, MD, and Leslie Cho, MD

Among the many factors to be considered in properly diagnosing and treating cardiovascular disease, the patient’s

mental health is perhaps the most overlooked. Cardiac events can be major sources of stress and anxiety, even after

they have been identified and abated.

Inmanycases,cardiaceventswillthrowpatientsfora

loop because these events represent an unexpected brush

withtheirmortality.Additionally,asubsetofpatients

who experience cardiac events have pre-existing depres-

sion or emotional issues that are exacerbated by the

ordeal of the cardiac event.

Despite traditional underappreciation of the impor-

tance of mental health in patients with heart disease,

cardiovascular medicine has progressed to the point

that patients’ emotional coping and wellness are now

increasingly managed along with their physical coping

and wellness.

Here at Cleveland Clinic, we operate a Cardiovascular

Behavioral Health Clinic in which behavioral health

services are located within the Section of Preventive

Cardiology and Cardiac Rehabilitation in our Heart &

VascularInstitute.Theclinicservesasaconsultation

service available to the patient, the treating cardiologist

and the patient’s primary care physician. This design and

structuring of the clinic within our cardiology service

stem from evidence that such co-location of services

improves the overall outcomes of patients with cardiovas-

cular disease.

identifying the need

Aspartofthestandardintakeprocess,patientsin

preventive cardiology and those enrolled in the cardiac

rehabilitation program are evaluated to determine how

well they are coping emotionally in the wake of cardio-

vascular surgery or other potentially traumatic therapies.

Quality-of-lifescorescoupledwithscreeningquestions

on depression and anxiety help determine which patients

stand to benefit from the Cardiovascular Behavioral

Health Clinic.

Such patients often have one or more telltale characteris-

tics, such as difficulty adhering to regimens for doctor’s

appointments, medication-taking and wellness activities

as well as difficulties with mental energy and social or

workengagements.Atthatpoint,itisnolongersufficient

for a cardiologist to simply tell them they are fine. Quality

of life can clearly be affected by physical and emotional

issues, which are common in patients with heart disease.

There is a need for psychiatric intervention, given the prev-

alence of depression after life-changing cardiac events.

Three Major Benefits of a Combined Clinic

Co-location of behavioral health services within a

cardiology clinic promises to yield at least three major

benefits:

• Itvalidateswhatpatientsarealreadyfeeling,helping

them understand that the care team is as interested in

their emotional well-being as in their blood pressure or

cholesterol level.

• Itoffersamorecomprehensiveapproachtodisease,

with the goal of ensuring greater long-term wellness

for patients.

• Itoftencontributestoamorewide-rangingsetofrec-

ommendations for optimal treatment simply by dint of

having behavioral health services under the same roof

Patients who stand to benefit from

such a clinic often have difficulty

adhering to regimens for doctor’s

appointments, medication-taking

and wellness activities.

B E H A V i o R A l H E A l t H i n C A R D i o V A S C u l A R D i S E A S E


as cardiology services. This is particularly the case for

many elderly patients, who may not want to visit the

psychiatry building because they perceive psychiatric

care as carrying a stigma.

Promoting Resiliency

Althougheachcaseisunique,somegeneralapproaches

to behavioral healthcare are efficacious for many patients

with cardiovascular disease. Chief among them may be

the importance of working with patients to recognize

their strengths and resiliency and to identify steps that

have helped them through difficult times earlier in their

lives. Those types of conversations are time well spent,

as they often help patients understand that they are

equippedtodealwiththestressofheartdisease.

AcliniclikeourCardiovascularBehavioralHealthClinic

can facilitate such conversations and ultimately help

promotepatients’recoveryandimprovetheirquality

of life. n

Dr. Pozuelo leads the Cardiovascular Behavioral Health

Clinic. He is Section Head of Consultation-Liaison Psychia-

try and Vice Chair, Clinical, in the Department of Psychiatry

and Psychology. He can be reached at 216.444.3583 or

[email protected].

Dr. Cho is Section Head for Preventive Cardiology and

Cardiac Rehabilitation and Director of the Women’s Cardio-

vascular Center in Cleveland Clinic’s Heart & Vascular Insti-

tute. She can be reached at 216.445.6320 or [email protected].

KEy PointS

the importance of mental health to the outcomes of patients with cardiovascular disease has traditionally been underappreciated, but that has started to change.

Cleveland Clinic operates a Cardiovascular Behavioral Health Clinic within a cardiology clinic to serve as a psychiatric consultation service to patients and their treating physicians.

The benefits of such a clinic include reassurance to patients that their providers care about their emotional well-being, a more comprehensive approach to heart disease and consideration of a wider range of treatment recommendations.

B E H A V i o R A l H E A l t H i n C A R D i o V A S C u l A R D i S E A S E


electroconvulsive therapy: underutilized Modality Can Be Safe, effective for Severe Mood Disorders in Adolescents

By Joseph Austerman, DO

Effective use of ECT has been demonstrated in adoles-

centssince1942.Yetdespitethelongevityofitsuseand

endorsementbytheAmericanAcademyofChildand

AdolescentPsychiatry,eCTremainshighlystigmatized

and misunderstood.

ECt Knowledge Gaps Persist

Even mental health professionals have knowledge gaps

abouttheuseofeCT.Inasurveyofchildpsychiatrists

andpsychologists,53.8percentreportedtheirknowledge

abouteCTtobeminimal,75percentsaidtheylacked

confidence in giving a second opinion about the treat-

mentmodalityand70percentregardeditasatreatment

of last resort.1

ECT also is not well understood by the public, and few

pediatricpatientsreceivethetreatment.Inastudyin

Switzerland,only1.2percentofarepresentativesample

ofthepublicwasinfavoroftheuseofeCT,and57percent

considered it a harmful treatment.2Inasurveyof113hos-

pitalsinAustralia,among7,469patientswhoreceived

eCT,only0.2percentwereyoungerthan18years.3

Electroconvulsive therapy (ECt) is a highly effective treatment modality for multiple psychiatric and medical illnesses.

Although commonly used in adults, this therapy is significantly underutilized in the adolescent population. Cleveland

Clinic is the only medical center in northeast ohio offering ECt for pediatric patients. the therapy is administered

here by a team of child and adolescent psychiatrists who are accredited in its use.

Determining Appropriate indications

The adult population is referred for ECT most often for

mood disorders, while adolescents are referred most

often for schizophrenia or schizoaffective disorders. This

contrasts with findings that the adolescent population

responds to ECT as well as, or even better than, the adult

population for mood disorders and psychosis, while

experiencing fewer or the same degree of side effects.

Substantial empirical evidence supports the benefit of

ECT in adolescents in severe, persistent mood disorders,

psychosis or catatonia. There also are multiple reports

demonstrating benefits for self-injurious behavior in

autistic spectrum disorders and Tourette syndrome.4

Aswithadults,eCTshouldbeconsideredinadoles-

cents when there are severe, persistent and significantly

disabling symptoms. Unless there is an urgent need,

such as the refusal to eat or drink, severe suicidality,

uncontrollable mania or florid psychosis, ECT should

be considered only after usual treatment modalities

havefailed.Thereshouldbeatleasttwoadequatetrials

of appropriate psychopharmacologic agents accompa-

nied by other appropriate treatment modalities such as

psychotherapy.2

Best Practices When Administering ECt

Adolescentpatientsshouldundergoafullpsychiatricand

medical evaluation in a standardized fashion when ECT

is being considered (Table 1).2 Collateral information

should be obtained from parents and treatment provid-

ers. Target symptoms should be assessed using reliable

rating instruments.

Before ECT is administered, a comprehensive physical

should be done that includes a complete blood cell count,

differential white blood cell count, thyroid function

test, liver function test, urinalysis and toxicology screen,

When considering ECT,

every patient should receive

an independent evaluation

from a psychiatrist who is

knowledgeable about ECT and

not directly responsible for

treatment of the patient.

A D o l E S C E n t P S y C H i A t R y


eCGandbrainCT.Aserumurinepregnancytestshould

beobtainedforfemales.Also,itisrecommendedthat

adolescents undergoing ECT have a memory assessment

before treatment. Permission must be obtained from the

parent/guardianandassentobtainedfromthechild.

When considering ECT, every patient should receive

an independent evaluation from a psychiatrist who is

knowledgeable about ECT and not directly responsible

for treatment of the patient. While supportive treat-

ment of adolescents should continue during the course

of ECT whenever possible, ECT should be administered

table 1. Recommended Assessment Protocol in Adolescents with Depression

Steps Actions/notes

Patient selection Symptoms are severe and persistent

failed at least two adequate antidepressant trials accompanied by other appropriate treatment modalities such as psychotherapy

Active suicidality, florid psychosis or life-threatening symptoms such as refusal to eat

Psychiatric assessment Detailed clinical interview incorporating past treatments

Reliable rating instruments administered

Second opinion obtained by a psychiatrist knowledgeable about eCt who is not treating the patient

Cognitive and memory assessment

Medical assessment Complete physical assessment

Laboratory data:• CBC with differential• Thyroid function test• Liver function test• Urinalysis and toxicology

Imaging:• ECG• EEG• CT

Anesthesia preoperative assessment

Consent Complete explanation of the procedure, risks, benefits and alternative treatments to both the patient and the parent/guardian

Monitoring Monitor patients during and after treatment until fully recovered from anesthesia

Monitoring should continue for at least 24 hours after the procedure

Cognitive assessment prior to acute eCt series, immediately after the acute series and three to six months after the acute series

Source: Based on recommendations in ghaziuddin et al2

without concurrent medications, as some psychotropic

medicationsmayaffectthequalityofeCTorconfera

neurocognitive risk with the concurrent use of ECT.2

low incidence of Side Effects

There are no absolute contraindications to the use

ofeCT;however,tumorsoftheCNSassociatedwith

increased cerebrospinal fluid pressure, active chest

infection or recent myocardial infarction are considered

relative contraindications.



AfewsideeffectsareassociatedwiththeuseofeCT,

the most common of which are transient: headaches,

delirium lasting less than one hour post-procedure,

hypomanic symptoms and memory loss. Cognitive

effects associated with ECT are comparable to those

in adults, and there are no data to support long-term

cognitive effects.

Oneraresideeffectmayincludetardiveseizuresarising

inthefirst20to48hoursaftereCTisadministered.This

effect was seen more often in those patients experiencing

aprolongedseizure(>180seconds).

Fatality is rare, with an overall fatality rate similar to

thatinadults(0.2per10,000).Theriskofanesthesiaand

complications is believed to be no greater than 1.1 per

10,000incidents,whichiscitedascomparabletotherate

for adults.2

Good Remission Rates in unipolar Depression

ECT in adolescents is most beneficial for the treatment

of severe mood symptoms, acute suicidality, catatonia

and psychosis. Some studies report a remission rate of

approximately60percentfortreatmentofrefractory

unipolar depression.3

AlthougheCTiscommonlymisunderstoodandstigma-

tized, it is a valid, safe and effective treatment modality

for adolescents suffering from mood or psychotic symp-

toms and should be considered as a rational treatment

option. n

RefeReNCeS

1. Shoirah H, Hamoda HM. Electroconvulsive therapy in children and adolescents. Expert Rev Neurother. 2011;11(1):127-137.

2.GhaziuddinN,KutcherSP,KnappP,etal;fortheAACAPWorkGrouponQualityIssues.Practiceparameterforuse of electroconvulsive therapy with adolescents. J Am Acad Child Adolesc Psychiatry.2004;43(12):1521-1539.

3.BlochY,Sobol,D,LevkovitzY,KronS,RatzoniG.Reasons for referral for electroconvulsive therapy: a comparison between adolescents and adults. Australas Psychiatry.2008;16(3):191-194.

4. Wachtel LE, Dhossche DM, Kellner CH. When is electroconvulsive therapy appropriate for children and adolescents? Med Hypotheses. 2011;76(3):395-399.

Dr. Austerman is a staff physician in Cleveland Clinic’s

Center for Pediatric Behavioral Health and Department of

Psychiatry and Psychology. He specializes in the acute care

of medically ill children who require hospitalization for

physical illnesses. He can be reached at 216.445.7656

or [email protected].

KEy PointS

electroconvulsive therapy (eCt) is safe and effective for adolescents with severe, persistent and disabling mood disorders.

this treatment modality remains underutilized and mis-understood, preventing patients from receiving effective treatment.

It is important to follow standard guidelines and care paths when referring adolescents for eCt.



Donald A. Malone Jr., MD

Director, Center for Behavioral Health

Professor and Chairman, Department of Psychiatry and Psychology

Manish Aggarwal, MD

Veena Ahuja, MD

Amit Anand, MD

Kathleen Ashton, PhD

Joseph M. Austerman, Do

Florian Bahr, MD

Sarah Banks, PhD, ABPP-Cn

Joseph Baskin, MD

Scott Bea, PsyD

Aaron Bonner-Jackson, PhD

Adam Borland, PsyD

Minnie Bowers-Smith, MD

Susan Albers Bowling, PsyD

Robert Brauer, Do

Dana Brendza, PsyD

Karen Broer, PhD

Robyn Busch, PhD

Kathy Coffman, MD

Gregory Collins, MD

Edward Covington, MD

Horia Craciun, MD

Roman Dale, MD

Syma Dar, MD

Sara Davin, PsyD, MPH

Ketan Deoras, MD

Beth Dixon, PsyD

Judy Dodds, PhD

Michelle Drerup, PsyD

Jung El-Mallawany, MD

Emad Estemalik, MD

tatiana Falcone, MD

lara Feldman, Do

Darlene Floden, PhD

Kathleen Franco, MD

Margo Funk, MD

Harold Goforth, MD

lilian Gonsalves, MD

Jennifer Haut, PhD, ABPP-Cn

Justin Havemann, MD

leslie Heinberg, PhD

Kelly Huffman, PhD

Karen Jacobs, Do

Joseph W. Janesz, PhD, liCDC

Amir Jassani, PhD

Jason Jerry, MD

Xavier Jimenez, MD

Daniel Jones, PhD

Regina Josell, PsyD

Elias Khawam, MD

Patricia Klaas, PhD

Steven Krause, PhD, MBA

Cynthia S. Kubu, PhD, ABPP-Cn

Richard lightbody, MD

Jane Manno, PsyD

Manu Mathews, MD

Michael McKee, PhD

Douglas Mclaughlin, Do

Julie Merrell, PhD

Amit Mohan, MD

Gene Morris, PhD

Douglas Moul, MD

Donna Munic-Miller, PhD

Kathryn Muzina, MD

Richard naugle, PhD

Mayur Pandya, Do

Michael Parsons, PhD

leopoldo Pozuelo, MD

Kathleen Quinn, MD

ted Raddell, PhD

laurel Ralston, Do

Stephen Rao, PhD

Joseph Rock, PsyD

Michael Rosas, MD

Robert Rowney, Do

Judith Scheman, PhD

isabel Schuermeyer, MD

Cynthia Seng, MD

Jean Simmons, PhD

Barry Simon, Do

Catherine Stenroos, PhD

David Streem, MD

Amy Sullivan, PsyD

Giries Sweis, PsyD

George E. tesar, MD

Mackenzie Varkula, Do

Adele Viguera, MD, MPH

John Vitkus, PhD

Kelly Wadeson, PhD

Cynthia White, PsyD

Molly Wimbiscus, MD

Amy Windover, PhD

Staff Listing | Center for Behavioral Health

CLeveL AnD CLInIC CenteR foR BeHAvIoRAL HeALtH | 866.588.2264

the Cleveland Clinic foundation 9500 euclid Avenue | AC311Cleveland, oH 44195

13

-neu

-586

Resources for Physicians

Physician Directory. view our staff online at clevelandclinic.org/staff.

Same-Day Appointments. Cleveland Clinic offers same-day appointments to help your patients get the care they need, right away. Have your patients call our same-day appointment line, 216.444.CARE (2273) or 800.223.CARE (2273).

track your Patients’ Care online. establish a secure online DrConnect account for real-time information about your patients’ treatment at Cleveland Clinic at clevelandclinic.org/drconnect.

Critical Care transport Worldwide. to arrange for a critical care transfer, call 216.448.7000 or 866.547.1467. Learn more at clevelandclinic.org/criticalcaretransport.

CME opportunities: live and online. visit ccfcme.org to learn about the Cleveland Clinic Center for Continuing education’s convenient, complimentary learning opportunities.

outcomes Data. view outcomes books at clevelandclinic.org/outcomes.

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About Cleveland ClinicCleveland Clinic is an integrated healthcare delivery system with local, national and international reach. At Cleveland Clinic, more than 3,000 physicians and researchers represent 120 medical specialties and subspecialties. We are a non-profit academic medical center with a main campus, eight community hospitals, more than 75 northern ohio outpatient locations (including 16 full-service family health centers), Cleveland Clinic florida, Cleveland Clinic Lou Ruvo Center for Brain Health in Las vegas, Cleveland Clinic Canada, Sheikh Khalifa Medical City and Cleveland Clinic Abu Dhabi.

In 2013, Cleveland Clinic was ranked one of America’s top 4 hospitals in U.S. News & World Report’s annual “America’s Best Hospitals” survey. the survey ranks Cleveland Clinic among the nation’s top 10 hospitals in 14 specialty areas, and the top in heart care for the 19th consecutive year.

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