The Chronicle of Neurology & Psychiatry Dec. 2014

M e t a b o l i c d i s o r d e r s

Possible cause of HSP discoverednMetabolic deficiency linked to hereditary spastic paraplegiaby John Evans, Assistant Editor, The Chronicle

WHILE NO TREATMENT CURRENTLY EXISTS FOR THE diverse set of neuro-genetic disorders identified as hereditary spastic paraplegia (HSP), ateam of researchers from Montreal and Jerusalem have identified a

severe deficiency in methylenetetrahydrofolate reductase (MTHFR) as the causeof a complicated form of adult-onset spastic paraplegia in four patients whoresponded to betaine therapy.

The paper, published in JAMA Neurology (July 2014; 71(7):901-904),looked at two pairs of siblings from unrelated

by Emily Innes, Assistant Editor, The Chronicle

ALTHOUGH ANTIEPILEPTICdrugs (AEDs) are notconsidered first line

treatment for agitation andaggression in dementiapatients, there is evidence thatcarbamazepine can be aneffective therapy in limited cir-cumstances, according to areview study in the journalDrugs (Sept. 20, 2014). Thestudy also reported that val-proate cannot be recommend-ed for this use.

Dr. Damien Gallagher, anassistant professor of geriatricpsychiatry at The University ofToronto and a co-author of the

study, said he conducted thisreview of AEDs to re-examinethe older medications—carba-mazepine and valproate—butalso to determine if some ofthe newer AEDs such as leve-tiracetam, oxcarbazepine,gabapentin, topiramate, andlamotrigine are possibly moreeffective than current first linetreatments. These includeantipsychotic medications andincreasingly, selective sero-tonin reuptake inhibitors anti-depressants.

“If there was a possibilitythat some of these medica-tions were more effective,might be better tolerated, and

The ChroNICle is committed to environmentallysustainable policies, and to encouraging“green aware” practices in healthcare. We arenow proud to provide this journal on thehighest percentage of recycled paper stockcurrently commercially available.

Editorial: Opioid use and misuse: an epidemic ........................3Depression: Remitted depression in mothers helpful for kids ..6Book review: ‘The Psychopath Inside’ ..................................17

Canada’s National Newspaper of the CNS Sciences n December 2014

In this issue’s Chronicle Vitae profile, Dr. Benoit Mulsantdiscusses his ongoing study on Alzheimer’s disease preven-tion, research that received a large grant presented by theprime minister of Canada. See page 18

S o c i a l m e d i a

Redefining professionalism in a digital ageSocial media can blur the boundaries between personal and pro-fessional identities for health care providers. Furthermore, thereare situations regarding professionalism that may be unique topsychiatry, according to a presentation at the CanadianPsychiatric Association’s 64th Annual Meeting. —See page 13

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We will be celebrating the 50th Congress of the Canadian Neurological Sciences FederationJune 9 – 12, 2015 at the The Fairmont Royal York Hotel in Toronto Ontario

We hope that you will join us for this special anniversary meeting!

A BRIEF HISTORY - The original Canadian Neurological Association wasestablished in 1948. The founding meeting was held in Montreal and wasattended by Wilder Penfield, Allan Waters, Walter Hyland, Jean Saucier,Francis McNaughton and Roma Amyot.

The first annual general meeting of this Association was held at the Royal YorkHotel in Toronto and was attended by 38 prospective members from acrossthe country. The association was established to represent neurology,neurosurgery and neurobiology and Dr. Wilder Penfield was named firstpresident. In 1949, the association was renamed the Canadian NeurologicalSociety.

The Canadian Neurological Society was dissolved in 1965 and two newsocieties were formed representing two distinct disciplines – the new CanadianNeurological Society for neurologists and the Canadian Neurosurgical Societyfor neurosurgeons. Together, their liaison committees planned the first annualjoint meeting held in 1965 – the first Canadian Congress of NeurologicalSciences.

In subsequent years, they were joined by the Canadian EEG Society (later named the Canadian Society of ClinicalNeurophysiologists) and the Canadian Association of Child Neurology.

The Canadian Congress of Neurological Sciences was formally incorporated in 1990 with a board of directorsrepresenting each of the four member societies, and with a permanent secretariat office in Calgary, Alberta. In2006, we became the Canadian Neurological Sciences Federation. The name was changed to better reflect thefact that the organization had been, for many years, a federation of four professional societies. This also helpedto distinguish the organization from its annual meeting, which is the Congress.

Now, in 2015, we are very proud to be hosting our 50th Congress and we are so pleased to be back at the RoyalYork Hotel in Toronto.

The Congress has seen many changes over 50 years and we are very proud of where we aretoday. We strive to provide a solid scientific program each year assisted by your input from theevaluations and the hard work of your colleagues on the Continuing Professional Developmentcommittee and the Scientific Program Committee.

Just as the CNSF has grown, the city of Toronto has also grown, surrounding the FairmontRoyal York Hotel. The hotel was built in 1929, and became a notable landmark. Themagnificent architecture of this hotel continues to grace the city’s skyline, and dominate thecity’s social scene.

Located in the heart of down-town Toronto, the Fairmont Royal York is just steps away fromthe best night life, dining, shopping and other attractions that the city has to offer. The hotelfeatures an indoor swimming pool, state-of-the-art exercise equipment, steam bath facilities andexceptional spa treatments. Come for the CNSF 50th anniversary Congress and the Royal Yorkwill ensure that your every need will be graciously met.

CNSF 50th Congress


PRESCRIPTION OPIOID USE HAS REACHED an alarmingproportion in Canada, the second largest consumer ofopioid analgesics in the world.1 Approximately

200,000 Canadians are regular users of prescription opioids.2In America, opioid sales increased by 627% between

1997 and 2007 with a corresponding increase in opioid-related deaths by 296%.3 Closer to home, in Ontario, theprovince with the greatest dispensing rate of high dose opi-oids,4 the number of oxycodone prescriptions increased by850% from 1991 to 2007.5

The upsurge in opioid prescriptions has increased theavailability of opioids for recreational drug use as well asdependency and addiction, paving the way for numerous

health and socialproblems includingopioid misuse, addic-tion, overdose, andmortality.6

The problemswith prescriptionopioid useare several

fold. To mention a few: theincreased availability of opi-oids with no restrictions onprescribers’ specialty orexpertise; lack of evidence-based guidelines and under-utilization of the currentlyavailable opioid prescription guide-

lines;7 and the lack of or limited access to alternative thera-pies (other than opioids) to manage pain conditions such ascognitive behavioural therapies, physiotherapy, lifestyle modi-fications, and occupational therapy.

Further problems with prescription opioid use includethe poverty of research on the comorbidity of pain and opi-oid addiction and predictors of response to treatment; exist-ing research that is highly variable with inconsistent findingsseen due to in part to the lack of standardized measurementtools to assess complex phenomena such as pain, addiction,and definition of treatment response; and the current strate-gies to reduce availability of opioids have not been effectivein modifying prescription patterns or the availability of opi-oids on the streets.

The last problem is the limited resources available forpolicing opioid prescription misuse.

Despite efforts to produce guidelines for prescribingopioids for managing chronic non-cancer pain,6 these guide-lines remain broad and lacking empirical evidence. Forexample in the recent position statement by the AmericanAcademy of Neurology, recommendations of avoiding highdoses of opioids “unless sustained meaningful improvementin pain” are vague at best.

In addition, suggestions such as discharging patientswho do not comply with the treatment contract can be dan-gerous as this may lead to serious opioid withdrawal symp-toms or pushing patients to obtain illicit opioids.

AAN GUIDELINE: NEED FOR ONGOING PATIENT MONITORINGNonetheless this position statement does provide a startingpoint to harmonize the practice of pain management andpoints prescribers in the right direction to use standardizedassessment tools and highlight the need for ongoing assess-ment of patient’s response to treatment.

In an ongoing study, in collaboration with the OntarioAddiction Treatment Centres and the PopulationGenomics Program at McMaster University in Hamilton,we are investigating the effectiveness of methadone fortreating opioid addiction and risk factors associatedwith ongoing illicit opioid use.7

Currently over 500 patients participated in thestudy with an average age of 36 years, and almost halfof patients in this study reported their first exposure to

opioids was through an opioid prescription. Among thestudy participants, 29% reported chronic pain despite a rela-tively young age. We have previously reported the impact ofchronic pain on response to treatment and have shown thatpatients with chronic pain and opioid addiction haveincreased interferon gamma levels (inflammatory marker)compared to patients without chronic pain.8 These findingsmay assist in encouraging research into the biomarkers ofpain and addiction and the selection of non-opioid basedtreatment options for chronic pain.

It is evident that the prescription opioid epidemic is outof control as seen in the increasing number of high doseopioid prescriptions throughout Canada,4 which is an under-estimation of the size of the problem since the studyfocused on high doses of opioids and excluded less fre-quently prescribed opioids.4 Despite the increasing aware-ness of opioid overuse, the dangers associated with long-term use and corresponding healthcare and social costs, weare not any closer to controlling the opioid epidemic.LIMITED KNOWLEDGE OF LONG-TERM IMPACT OF OPIOIDSPart of the problem can also be attributed to a poor publichealth strategy and approval of opioids by Health Canadawith limited knowledge of the impact in the longer term.For example, the replacement of OxyContin with

The Chronicle of Neurology & Psychiatry is published six times annually by the proprietor, Chronicle Information Resources Ltd., with offices at555 Burnhamthorpe rd., Ste. 306, Toronto, ont. M9C 2Y3 Canada. Telephone: 416.916.2476; Fax. 416.352.6199. e-mail: [email protected].

Contents © Chronicle Information Resources Ltd., 2014, except where noted. All rights reserved worldwide. The Publisher prohibits repro-duction in any form, including print, broadcast, and electronic, without written permissions. Printed in Canada. Mail subscriptions: $72 per year inCanada, $125 per year in all other countries. Single copies: $12 per issue (plus 13% hST)

Canada Post Canadian Publications Mail Sales Product Agreement Number 40016917The Publisher certifies that advertising placed in this publication meets revenue Canada requirements for tax deductibility.Volume 17, Number 6, published December 2014ISSN 1209-0565

Guest editorial: The epidemic of opioid use and misuse

December 2014 n 3

“Listening is a magnetic and strange thing, a creative force.The friends who listen to us are the ones we move toward. When we are

listened to, it creates us, makes us unfold and expand.” —Dr. Karl A. Menninger, U.S. psychiatrist (1893-1990).

R e s e a r c h

n researchers have found that a previ-ous diagnosis of obsessive-compul-sive disorder (oCD) is a risk factorfor schizophrenia. The authors ofthe study published in JAMAPsychiatry (Nov. 2014; 71(11):1215-1221) note that the link betweenoCD had been observed but notunderstood. The presence of priordiagnosis of oCD was associatedwith an increased risk of developingschizophrenia (Irr=6.90; 95% CI,6.25-7.60) and schizophrenia spec-trum disorders (Irr=5.77; 95% CI,5.33-6.22) later in life.

—Find more info at http://ow.ly/EZwN1

n hypovitaminosis D was associated withcognitive decline in a 1,927 elderlyItalian population over a 4.4 year fol-low-up. Participants with a Serum 25-hydroxyvitamin D level deficiency(<50 nml/l) or insufficiency (50-70nmol/l) showed declining Mini-Mental State examination scores,according to the study published inthe journal Neurology (Nov. 5, 2014).

—Find more info at http://ow.ly/BRZNs

n Investigators found a disruption ofwhite matter microstructure in asmall population of women withanorexia nervosa compared to acontrol group. Patients with anorex-ia nervosa showed significant frac-tional anisotropy decreases in theparietal part of the left superior lon-gitudinal fasciculus (SlF; pFWe <0.05), with increased mean diffusiv-ity and radial diffusivity but no differ-ences in axial diffusivity, accordingto a study published in The Journalof Psychiatry and Neuroscience(Nov. 2014; 39(6):367-375).

—Find more info at http://ow.ly/EZFKm

n Continuous positive airway pressuretreatment of severe sleep apneasyndrome in patients with mild-to-moderate Alzheimer’s disease wasassociated with significantly slowercognitive decline, according to astudy in the Journal of Neurology,Neurosurgey, & Psychiatry (Dec.2014; 85(12):1405-1408).

—Find more info at http://ow.ly/EZGO3

We will be celebrating the 50th Congress of the Canadian Neurological Sciences FederationJune 9 – 12, 2015 at the The Fairmont Royal York Hotel in Toronto Ontario

We hope that you will join us for this special anniversary meeting!

A BRIEF HISTORY - The original Canadian Neurological Association wasestablished in 1948. The founding meeting was held in Montreal and wasattended by Wilder Penfield, Allan Waters, Walter Hyland, Jean Saucier,Francis McNaughton and Roma Amyot.

The first annual general meeting of this Association was held at the Royal YorkHotel in Toronto and was attended by 38 prospective members from acrossthe country. The association was established to represent neurology,neurosurgery and neurobiology and Dr. Wilder Penfield was named firstpresident. In 1949, the association was renamed the Canadian NeurologicalSociety.

The Canadian Neurological Society was dissolved in 1965 and two newsocieties were formed representing two distinct disciplines – the new CanadianNeurological Society for neurologists and the Canadian Neurosurgical Societyfor neurosurgeons. Together, their liaison committees planned the first annualjoint meeting held in 1965 – the first Canadian Congress of NeurologicalSciences.

In subsequent years, they were joined by the Canadian EEG Society (later named the Canadian Society of ClinicalNeurophysiologists) and the Canadian Association of Child Neurology.

The Canadian Congress of Neurological Sciences was formally incorporated in 1990 with a board of directorsrepresenting each of the four member societies, and with a permanent secretariat office in Calgary, Alberta. In2006, we became the Canadian Neurological Sciences Federation. The name was changed to better reflect thefact that the organization had been, for many years, a federation of four professional societies. This also helpedto distinguish the organization from its annual meeting, which is the Congress.

Now, in 2015, we are very proud to be hosting our 50th Congress and we are so pleased to be back at the RoyalYork Hotel in Toronto.

The Congress has seen many changes over 50 years and we are very proud of where we aretoday. We strive to provide a solid scientific program each year assisted by your input from theevaluations and the hard work of your colleagues on the Continuing Professional Developmentcommittee and the Scientific Program Committee.

Just as the CNSF has grown, the city of Toronto has also grown, surrounding the FairmontRoyal York Hotel. The hotel was built in 1929, and became a notable landmark. Themagnificent architecture of this hotel continues to grace the city’s skyline, and dominate thecity’s social scene.

Located in the heart of down-town Toronto, the Fairmont Royal York is just steps away fromthe best night life, dining, shopping and other attractions that the city has to offer. The hotelfeatures an indoor swimming pool, state-of-the-art exercise equipment, steam bath facilities andexceptional spa treatments. Come for the CNSF 50th anniversary Congress and the Royal Yorkwill ensure that your every need will be graciously met.

CNSF 50th Congress

Dr. Zainab Samaan is an associate professor in the Department ofPsychiatry and Neuroscience and an associate member of theDepartment of Clinical Epidemiology and Biostatistics and FacultyPopulation Program at McMaster University in Hamilton. Dr.Samaan is the acting supervisor for McMaster doctoral studentsMonica Bawor, MiNDS Neuroscience Program in the Faculty ofHealth Sciences, and Brittany Dennis, Health Research Methodologyprogram in the Department of Clinical Epidemiology and Biostatistics. —Editorial continued on page 12

ABOUT THE AUTHORS

Dr. Samaan Dennis

Bawor


4 n December 2014

s Atelier: This powerful image was created by a 53-year-old woman who had recentlyended a marriage of 23 years. She was struggling with intense feelings of angerand betrayal. She explained that the bright red border, covered with sharp, point-ed lines, represents deep feelings of rage. The inner shape represents her innercore, which is plagued with feelings of fear and low self-esteem. She described itas a swirling egg that could easily break. She explained, “The green colour rep-resents my naiveté. The purple represents an uneasy, almost queasy feeling. Iblindly believed his lies, but I always felt something was not right. Now I wear myanger like a protective coat. I am not volatile, I’m just always boiling, but it is adefense. I am trying to protect myself.” The process of creating artwork can allowfor the cathartic release of tension. Examining the finished piece with the art ther-apist provides opportunities for the client to make emotional connections to theimages, process intense emotions, and gain personal insight.

—Andrea Charendoff, registered art therapist, Toronto—More information on Andrea Charendoff and her work is available at

www.speakingthroughart.ca

s Quick-start guide to The Chronicle, December 2014:

Publication Indexn Depression: Remitted depression in mothers is beneficial for

children (p. 6)n Dementia: WHO links tobacco and second-hand smoke with

increased dementia risk (p.11)n Over-prescribed opioids: Various reports suggest physicians over-

prescribe opioids (p. 12)n Metabolic disorders: Night eating syndrome associated with poor

metabolic health, higher BMI (p. 15)n Book review: The Psychopath Inside: A Neuroscientist’s Personal Journey Into

the Dark Side of the Brain (p. 17)n Chronicle Vitae: Dr. Benoit Mulsant receives substantial grant for

Alzheimer’s disease prevention research (p. 18)

Founding EditorRichard Gladstone,

MD, FRCPCPsychiatry Editor

J. J. Warsh, MD, FRCPCEditor, Innovation in the Mind Sciences

Roger S. McIntyre, MD, FRCPC

Editorial DirectorR. Allan Ryan

Senior Associate EditorLynn Bradshaw

Assistant EditorsJohn EvansEmily Innes

PublisherMitchell Shannon

Production and CirculationCathy Dusome

Sales & MarketingSandi Leckie, RN

ComptrollerRose Arciero

PEOPLE WITH MENTAL ILLNESS such asschizophrenia, schizoaffective disorderor bipolar disorder use video sharingwebsites like YouTube to provide andreceive peer support, researchersreport in the journal PLOS ONE (Oct.15, 2014).

“What we found most surprisingabout our findings was that peoplewith severe mental illness were soopen about their illness experiences on apublic social media website likeYouTube,” stated lead author JohnNaslund, a PhD candidate in health poli-cy at The Dartmouth Institute for HealthPolicy and Clinical Practice in Lebanon,N.H., in a press release.

Naslund and colleagues found thatpeople with severe mental illness usedYouTube to feel less alone and to findhope, to support and to defend each other,and to share personal stories and strate-gies for coping with day-to-day chal-

lenges. They also sought to learn from theexperiences of others about using med-ications and seeking mental health care.SPACE TO OVERCOME FEARS“It helps them to overcome fears associatedwith living with mental illness, and it alsocreates a sense of community among theseindividuals,” the researchers said.

The researchers used a methodcalled online ethnography to analyse3,044 comments posted to 19 videosuploaded by individuals who self-identifiedas having schizophrenia, schizoaffective

disorder, or bipolar disorder. They thenused qualitative methods to analysethe comments and find commonthemes in the data.

“What is also important is that ourfindings are consistent with how peersupport is viewed in mental healthresearch and practice, which suggeststhat YouTube or other social mediawebsites might help to extend the

reach of informal peer support activitiesbetween people with severe mental ill-ness,” said Naslund.

The research does have limitations,however, in that the work was exploratory.“Therefore, it was not possible for us todetermine whether YouTube can providethe benefits of peer support to a widercommunity of individuals with severe men-tal illness,” he said.

—Read more information at http://ow.ly/Eiw8h orhttp://ow.ly/EiwuQ

Community support on YouTube for those with mental illneses


December 2014 n 5

“But there was no need to be ashamed of tears,for tears bore witness that a man had the

greatest of courage, the courage to suffer.”—Dr. Viktor Emil Frankl, Austrian neurologist (1905-1997).

I n t h e n e w s . . .

n In a sample size of 7,000 U.S. fire-fighters, 37% screened positivefor a sleep disorder, according toa study published in the Journalof Clinical Sleep Medicine. In80% of these cases the sleepingdisorder was undiagnosed. Thisis concerning because the fire-fighters with the sleeping disor-der were more likely to reportfalling asleep at the wheel whiledriving and other health condi-tions such as anxiety, depres-sion, and cardiovascular dis-ease, reports Tech Times (Nov.14, 2014).

—Read this article athttp://ow.ly/EpCWi

n Danish researchers had an 86%success rate in triggeringmigraines in a 14 person study.The investigators used cyclicAMP to cause the migraine andthese findings might help todevelop better targeted treat-ments, reports The WashingtonPost (oct. 31, 2014).

—Read this article athttp://ow.ly/Eqf1f

n A Swedish study has found thatthose who had talked on a cellphone or cordless phone for 25years had triple the risk ofdeveloping brain cancer thanthose who had only been usinga wireless phone for a year,reports The Globe & Mail (Nov.12, 2014).

—Read this article athttp://ow.ly/ExdkA or

http://ow.ly/ExelI

n In reversal of its previous decisionto reject alemtuzumab(lemtrada), the United State’sFood and Drug Administration(FDA) has approved the drug forthe treatment of relapsing-remit-ting multiple sclerosis for sale inthe U.S. The FDA will requirealemtuzumab’s packaging to con-tain prominent warning labels ofthe drug’s potential side effects—including fatal autoimmune condi-tions and a possible increasedrisk of cancer, reports The WallStreet Journal (Nov. 15, 2015).

—Read this article athttp://ow.ly/Exiby

EXPERIMENTS per-formed in rat modelsof Parkinson’s disease

revealed that the latestdeveloped version of stemcell-derived dopamine cellsfully mimic the characteris-tics and function of thedopamine neurons that arelost in Parkinson’s disease.The potentially unlimitedsupply of transplantablecells, sourced from stemcell lines, opens the door toclinical application on a much broaderscale, report the authors in their studythat was published in the journal Cell StemCell (Nov. 6, 2014; 15(5):653-665).

“This study shows that we can nowproduce fully functioning dopamineneurons from stem cells. These cellshave the same ability as the brain’s nor-mal dopamine cells to not only reach butalso to connect to their target area overlonger distances,” said Malin Parmar, anassistant professor who led the studyconducted at Lund University inSweden. “This has been our goal forsome time, and the next step is to pro-duce the same cells under the necessaryregulations for human use. Our hope isthat they are ready for clinical studies inabout three years.”

SELECT PATIENTS TO GET CELLS SOONBrain cell transplants with fetaldopamine cells obtained from humanembryos have already been performedon a few occasions, with varying results.In the coming months a small numberof patients will be transplanted withfetal cells in Lund and Cambridge, U.K.

The fetal dopamine cells that will beused within TRANSEURO, a Europeanresearch consortium involved in thestudy, however, they carry some restric-tions. First, there is the ethical concern of

taking tissue from aborted fetuses.There is also the issue of availability offetal cells, which are often scarce. Thelogistics surrounding the gathering ofcells for any specific transplantation ispartly limited to luck and circumstance.These concerns will be resolved as thestem cell-derived dopamine cells becomeavailable in the clinic, making the treat-ment accessible for larger patient groups.

Getting stem cells to become func-tioning dopamine neurons, the method ofdelivering them to a specific target, andlearning how to get them to integrate inthe brain, are all extremely complicatedprocesses. The sharing of ideas and datahas been integral to the success of thesenetworks, explains professor ElenaCattaneo, coordinator forNeuroStemcellRepair, a EU network alsoinvolved in the research.

“Collaborative research of thisnature is so much more than the results itproduces, especially if we consider itspotential for expanding the boundaries ofknowledge and dissolving cultural barri-ers. From this perspective, basic researchand collaboration among nations standout once more as something the scientif-ic community should never distance itselffrom,” she stated in a press release.

—Read more information at http://ow.ly/ExN2q

HEALTH CANADA HAS APPROVEDvortioxetine hydrobromide forthe treatment of major depres-

sive disorder (MDD), to be available inDec. 2014.

Vortioxetine hydrobromide is anagent indicated for the treatment ofMDD in adults. It is an inhibitor ofserotonin (5-HT) reuptake and also anagonist at 5-HT1A receptors, a partialagonist at 5-HT1B receptors and anantagonist at 5-HT3, 5-HT1D and 5-HT7 receptors.

The efficacy of vortioxetinehydrobromide in maintaining anantidepressant response, with symp-tomatic relief, for up to 24 weekswas demonstrated in a controlledtrial in patients with MDD who ini-tially responded to an acute, openlabel treatment with vortioxetinehydrobromide.

DIVERSE SYMPTOMS IN DEPRESSIONREQUIRES DIVERSE TX OPTIONS“MDD manifests itself through awide array of emotional, physicaland cognitive symptoms,” stated Dr.Roger McIntyre, professor in theDepartments of Psychiatry andPharmacology at the University ofToronto and Head of the MoodDisorders PsychopharmacologyUnit at the University HealthNetwork, in a press release. “Beyondthe mood component, changes inappetite and psychomotor activity,difficulty concentrating and makingdecisions, or even suicidal behav-iour, are common. These symptomscan be felt by sufferers on a dailybasis, often throughout the day, andseriously impede their ability tofunction.”

“With such a diverse group ofsymptoms, it is important to finddiversity in treatment to improvepatient outcomes.”

A more in depth article willappear in an upcoming issue of THECHRONICLE OF NEUROLOGY + PSYCH -IATRY.

Non-proprietary and brand name oftherapy: vortioxetine hydrobromide(Trintellix, lundbeck Canada Inc.)

New major depressivedisorder treatmentcoming to Canada

PD: Stem cell derived dopamine cells n researchers engineer stem cell-derived dopamine cells thatfully mimic dopamine neurons lost in Parkinson’s disease patients

Courtesy of M

alin Parm

ar

Stem cell transplants for Parkinson’s diseaseIn this video, associate professorMalin Parmar, and researcherAgnete Kirkeby, of Sweden’s LundUniversity, discuss their study wherethey generated stem cells that func-tion equally well as those in the brain. They expectto engineer dopamine cells for Parkinson’s diseasepatients. http://ow.ly/ExK7S


6 n December 2014

by Louise Gagnon,Correspondent, The Chronicle

CHILDREN BENEFIT WHEN THEIR MOTHER with depression issuccessful in remitting their condition with pharmacologicaltreatment, according to data presented at the annual meeting

of the Anxiety and Depression Association of America in Chicago.Dr. Daniel Pilowsky, an assistant professor at Columbia

University Medical Center of Epidemiology and ColumbiaUniversity Medical Center of Psychiatry in New York City,described findings from a sub-study of a larger investigation oftreating depression in mothers during the meeting in Mar. 2014.

“There were statistically significant changes in parentingamong the mothers who remitted,” said Dr. Pilowsky. “We didnot see statistically significant changes in parent mothers whodid not remit or remitted but then relapsed.”

Successful treatment of maternal depression resulted in sig-nificant changes in depressive symptoms in children, noted Dr.Pilowsky.

The study involved two sites, New York City and Ottawa,and investigators had to take into account variables like socio-economic status: parents in Ottawa were generally middle-classand members of two-parent families while depressed patients inNew York City were generally low-income and single parents.

Dr. Pilowsky and colleagues focused on parenting andremission of depression. The primary study determined if thecombination treatment of escitalopram and bupropion led tomore rapid remission of depression in women than either agentas a monotherapy. The three-arm study saw women take eitherescitalopram for 12 weeks, bupropion for 12 weeks, and thecombination of the two for 12 weeks.

Investigators used the Montgomery-Asberg DepressionRating Scale and required a score of 22 to randomize patients toone of three treatment arms. Patients were dosed to a maximumof 450 mg per day of bupropion and/or 40 mg per day of esci-talopram for 12 weeks. Remission was defined as a score ofseven or less on the Hamilton Rating Scale for Depression.

The main study failed to show that dual therapy was superi-or in performance to either monotherapy approach in timing ofremission or remission rate (J Psychiatr Res May 2014; 52:7-14).

“It turned out that women who took the combination [ther-apy] did about the same [as the other women on a monothera-py],” said Dr. Pilowsky. “Our interest was determining how chil-dren did if their mothers did better, regardless of the drug thatmother took during the study.”

Women in the study were followed for up to nine monthsafter 12 weeks of active treatment. They were categorized as eitherremitting their disease, remitting but then relapsing within ninemonths, or failing to remit at all. Children of the mothers rangedin age from seven to 17 years, with almost half being female.

DECREASED DEPRESSION CAN IMPROVE PARENTING“When someone becomes less depressed, that individual’s par-enting is enhanced,” said Dr. Pilowsky. “This only explains inpart, however, the benefit to the children.”

Dr. Pilowsky noted that previously published researchfound severity of depression in mothers was predictive ofbehavioural problems in children (J Am Acad Child AdolescPsychiatry Nov. 2012; 51(11):1185-1196).

“We have not yet done studies of doing something other

than treating the mother [for depression], but our data suggeststhat parenting [should be] an area of focus,” said Dr. Pilowsky.“We find that parenting mediates, in part, the effects of remis-sion of maternal depression on the children.”

Anecdotally, it appears the impact of remission of depressionin women is greater on children in grade school than teenagedchildren, said Dr. Pilowsky. “Teenaged children are more affectedin their behaviour by their peers than by their parents,” he said.

Future research may demonstrate parenting interventionsmay complement the depression treatment of parents.Depression treatment, combined with parenting interventions,may prove effective in improving the psychopathological symp-toms of children, according to Dr. Pilowsky.

DIFFICULT TO RECRUIT FATHERS FOR DEPRESSION STUDIESDr. Pilowsky and colleagues also recruited fathers with depres-sion, but their sample size was too small to yield meaningfulresults. There is an ongoing challenge to recruit fathers withdepression for studies about parental depression and the impacton parenting, he noted.

“It is difficult to recruit men for these studies,” he said.“Depressed men seek treatment less than depressed women.”

The current research highlights that treating children’smoods and behaviour is not necessarily sufficient for improvingthe mood and behaviour of children with psychopathologicalsymptoms, but treating conditions in parents or caregivers ofchildren, be it depression and any co-morbidities that occur likeanxiety and substance abuse, will have a spin-off effect on chil-dren, improving their moods and behaviour as a consequence.

Non-proprietary and brand names of therapies: escitalopram(Cipralex, lundbeck Canada Inc.); bupropion (Wellbutrin, ValeantCanada).

Remitted depression in mothers is beneficial for childrenn Depression Tx with parenting interventions can improve mood, behaviour of children

Morguefile



THE BIDIRECTIONAL RELATIONSHIP between meta-bolic disorders and depression means that physi-cians should be screening for depression in adult

patients who present with metabolic disorders likeobesity and diabetes, according to a professor in theDepartments of Psychiatry and Pharmacology at theUniversity of Toronto.

“We have reason to believe that the underlyingpathophysiology/pathogenesis of diabetes and obesi-ty is overlapping with the pathophysiology/pathogen-

esis of depression,” said Dr.Roger McIntyre, during a presen-tation at Primary Care Today2014 in Toronto about novelinsights into depressive disor-ders. He is also the head of theMood Disorders PharmacologyUnit at the University HealthNetwork in Toronto.

One study Dr. McIntyre ref-erenced looked at electroencephalographic activityand found similar neurophysiological abnormalitieswitnessed in both diabetes mellitus and major depres-sive disorder (Journal of Neuropsychiatric Disease andTreatment 2013; 9:143-150).

Because of this overlap, there is an investigationunderway to repurpose pharmacotherapies designedto manage diabetes as pharmacotherapies to treatdepression. Glucagon-like peptide-1 receptor ago-nists, when administered in animal models, have beenshown to reduce depressive behaviour, and these ther-apies represent an integrated treatment direction that

would address metabolic conditions and mood disor-ders (Behav Brain Res Jan. 15, 2013; 237:164-171).

Patients who present with major depressive disorderhave elevated rates of obesity and metabolic disorderswhile at the same time patients with obesity and diabetesare more susceptible to depression, said Dr. McIntyre.

He urged that clinicians should screen obesepatients with type II diabetes for depression and apatient with depression should be screened for meta-bolic disturbances.

BODY WEIGHT, BMI PREDICTOR FOR IMPROVEMENTIN SYMPTOMS IN PATIENTS WITH DEPRESSIONRecently published research points to a link betweenbody weight and body mass index as predictors ofimprovement in symptoms in patients with majordepressive disorders, with non-remitters havinggreater body weight and body mass index pre-treat-ment (J Affect Disord June 2014; 161:123-126).

In research circles, the view of depression hasbroadened in the last decade such that it is no longerregarded as a clinical presentation resulting from a sin-gle mechanism, said Dr. McIntyre.

There is limited “evidence in the last severaldecades to support that major depressive disorder is aserotonin depletion disorder,” said Dr. McIntyre.

The emergence of depressive disorders is areflection of dysregulated brain circuitry, he said.

Neuroimaging investigations have revealed thatpatients with depression displayed an enhanced amyg-dala response to negative or fear-related stimuli (BiolPsychiatry Feb. 15, 2008; 63(4):377-384).

“Patients with major depressive disorder who areactively symptomatic

Patients with obesity and diabetes need to be monitored for depressionn exploring the bidirectional relationship between major depressive disorder and obesity or metabolic disorders

December 2014 n 7

Dr. McIntyre

We have reason to believe thatthe underlying pathophysiology/pathogenesis of diabetes andobesity is overlapping with thepathophysiology/pathogenesis

of depression.—Dr. roger McIntyre, professor in the Departments of

Psychiatry and Pharmacology at theUniversity of Toronto

The rIghT ANTerIor INSUlA has been found to be smaller in school-age children previously diagnosed with depression and also chil-dren who had previously been diagnosed with pathological guilt,according to a study published in JAMA Psychiatry (Nov. 12, 2014).

researchers from the University School of Medicine in St.louis followed a group of children in the Preschool DepressionStudy, conducted by investigators led by Dr. Joan l. luby, direc-tor of Washington University School of Medicine’s earlyemotional Development Program. The children were assessedfor depression and guilt each year from ages three to six years.

There were 47 diagnosed with depression as preschoolers,and 82 who had not been depressed. Some 55% of those withdepression had displayed pathological guilt as preschoolers,while 20% of the non-depressed group had excessive guilt.

All of the children also had MrI brain scans about every 18months from ages seven to 13 years.EXCESSIVE GUILT RELATED TO DEPRESSION, INSULA SIZEThis study’s findings provide evidence that excessive guilt is asymptom of depression related to the size of the insula.

“That’s not a complete surprise because for many years now,excessive guilt has consistently been a predictor of depression and amajor outcome related to being depressed,” stated first authorAndrew C. Belden, PhD, an assistant professor in the Department ofPsychiatry (child) at Washington State University, in a press release.

Pathological guilt can be a symptom of clinical depression, as well as other psychiatricdisorders including anxiety, obsessive-compulsive disorder, and bipolar disorder. Dr. Beldensaid it is relatively easy to spot the problem in children because they excessively blame

themselves for things they have done and have not done.“A child with pathological guilt can walk into a room and see a

broken lamp, for example, and even if the child did not break it, heor she will start apologizing,” Dr. Belden explained. “even afterbeing told he or she is not at fault, the child will continue to apolo-gize and feel bad.”

The “million-dollar question,” he said, is whether depressedchildren become more prone to guilt or guilt-prone children are morelikely to become depressed. either way, Dr. Belden noted, the dis-covery that pathological guilt is related to changes in the brain thatincrease the risk for recurrent depression could be a major step inbetter understanding the trajectory of depression.

The researchers found that children with a smaller insula in theright hemisphere of the brain—related either to depression orexcessive guilt—were more likely to have recurrent episodes of clin-ical depression as they got older.

“Arguably, our findings would suggest that guilt early in life pre-dicts insula shrinkage,” Dr. Belden said. “I think the story is begin-ning to emerge that depression may predict changes in the brain,and these brain changes predict risk for recurrence.”

The research suggests that excessive guilt and depression mayput preschoolers on a developmental trajectory that contributes toproblems with depression later in childhood and even throughout

life. Some children experience depression, recover and never have another episode, butothers experience a chronic and relapsing course. It is important to identify those whoare at risk for chronic and relapsing depression, according to Dr. Belden.

—Read more information at http://ow.ly/EiE1j

Insula smaller in children who had a previous diagnosis of depression, guilt


The anterior insula on each side of the brain(red) is smaller in children diagnosed withdepression as preschoolers and kids whoexperienced excessive guilt as very young chil-dren. A research team led by Andrew C.Belden, PhD, found that those with a smallerinsula in the brain’s right hemisphere weremore likely to have recurrent episodes ofdepression as they got older.

Photo courtesy of W

ashington University S

chool of Medicine St. Louis


AVONEX, TYSABRI, BIOGEN IDEC and the BIOGEN IDEC logo are registered trademarks of Biogen Idec. TECFIDERA and BIOGEN IDEC ONE are trademarks of Biogen Idec. FAMPYRA is a trademark of Acorda Therapeutics Inc.

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AVONEX, TYSABRI, BIOGEN IDEC and the BIOGEN IDEC logo are registered trademarks of Biogen Idec. TECFIDERA and BIOGEN IDEC ONE are trademarks of Biogen Idec. FAMPYRA is a trademark of Acorda Therapeutics Inc.

© 2014 Biogen Idec.

Call the Biogen Idec ONE™ Program at 1-855-MSONE-00 (1-855-676-6300)

TECFIDERA is a trademark of Biogen Idec. BIOGEN IDEC and the BIOGEN IDEC logo are registered trademarks of Biogen Idec. © 2014 Biogen Idec.

TECFIDERA™ (dimethyl fumarate) is indicated as monotherapy for the treatment of relapsing remitting multiple sclerosis (RRMS) to reduce the frequency of clinical exacerbations and to delay the progression of disability.

For more information:Consult the Product Monograph at http://www.biogenidec.ca/product_portfolio.aspx?ID=14979

for contraindications, warnings, precautions, adverse reactions, interactions, dosing, and conditions of clinical use. The Product Monograph is also available

by contacting Biogen Idec Canada Inc. at 1-866-359-2502.

REFERENCE: 1. TECFIDERA Product Monograph. October 23, 2014, Biogen Idec Canada Inc.

TECFIDERA is now covered on nine provincial plans and most private drug plans!

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reSeArCherS hAVe DeFINeD AND establishedcriteria for a new neurological diseaseclosely resembling Alzheimer’s disease(AD) called primary age-related tauopathy(PArT), according to a study published inthe journal Acta Neuropathologica (Dec.2014; 128(6):755-766).

Investigators from the U.S., Canada,europe, and Japan came together to for-malize criteria for diagnosing this new neu-rological disorder. The study establishesthat PArT is a primary tauopathy, a diseasedirectly caused by the tau protein in tangles.Many of the neurofibrillary tangles in ADbrain, in contrast, are thought to arise sec-ondarily to amyloid or some other stimuli.The researchers propose that individuals

who have tangles resembling those found inAD but have no detectable amyloid plaquesshould now be classified as PArT.

“To make an AD diagnosis you need tosee two things together in a patient’s brain:amyloid plaques and structures called neu-rofibrillary tangles composed of a proteincalled tau,” said Dr. Peter T. Nelson, a pro-fessor of neuropathology at the University ofKentucky’s Sanders-Brown Center on Agingin lexington, Ky. “however, autopsy studieshave demonstrated that some patients havetangles but no plaques and we’ve long won-dered what condition these patients had.”

PArT is most severe in patients ofadvanced age, but is generally mild inyounger elderly individuals. The reason for

this is currently unknown, but unlike AD, inwhich the tangles spread throughout thebrain, in PArT cases the tangles arerestricted mainly to structures importantfor memory, stated the authors.

DIAGNOSTIC TEST CAN NOW CHECKFOR AMYLOID AND TAU BIOMARKERSNew diagnostic tests using brain scansand cerebrospinal fluid biomarkers foramyloid and tau are finding surprisinglyhigh proportions of patients (as many as25% in some studies) with mild cognitiveimpairment that are positive for tau butnegative for amyloid.

—Read more information athttp://ow.ly/EoTcz

Criteria defined for new neurological memory related disorder

10 n December 2014

did not have some of the complications that the antipsychot-ic medications have then that would be really important froma patient care point of view,” said Dr. Gallagher. “Because thefirst line treatments have their limitations there is this contin-ual search for a medication that is safer and better tolerated.”

The authors, however, concluded that there is not enoughclinical data or evidence to support the use of the new AEDsto treat agitation and aggression in dementia. They do advo-cate for more investigation into these drugs for this indication.

Aggression and agitation occur in some form of severityin about 40% to 60% of patients with dementia during theirillness. This is often the most stressful and difficult complica-tion of the illness that caregivers report.

“It can vary from anything on the spectrum of restlessness,pacing, and agitation, to more extreme distress and physicalaggression where an individual may put themselves and theircarers at risk,” said Dr. Gallagher.

AED USED WHEN FIRST LINE TREATMENT NOT TOLERATEDDr. Gallagher said that there is some limited evidence to sup-port the use of carbamazepine in situations where other firstline treatments are not tolerated or are ineffective. In circum-stances where AEDs are prescribed, they would ordinarily beinitiated by a specialist who would start at a low dose and titrateupward slowly and gradually as needed. The patient should thenbe closely monitored for evidence of improvement and sideeffects, said Dr. Gallagher. Adverse effects associated with carba-mazepine include sedation, disorientation, and gait disturbance.If treatment benefits are outweighed by side effects then themedication should be discontinued

“In recent years there have been more studies of val-proate, which is the other AED that might have been morecommonly considered, and there is now more consistent evi-dence that it cannot be recommended for aggression and agi-tation because any observed benefits have been small and out-weighed by adverse effects,” said Dr. Gallagher. “I think thatis an important point from the paper that there is now moreconsistent evidence that valproate cannot be recommendedfor this indication.”

While pharmacological therapies are available, Dr.

Gallagher emphasized the first approach is “person centeredcare” that involves trying to address any unmet needs thatmight be causing the patient’s distress. The patient could haveenvironmental concerns, communication difficulties with acaregiver, or a general medical problem.

PERSON-CENTRED APPROACH SHOULD COME FIRST“If there are ways that we can intervene to make environmentalchanges such as reducing noise or overcrowding and increasingstimulation during the day so they are not bored or frustrated,that is usually the first line measure,” said Dr. Gallagher. “Thenwe might look at how the caregiver communicates with thepatient to ensure that the caregiver is not inadvertently exacer-bating the patient’s anxiety or stress.” Additional home andcommunity supports are often appropriate to help relieve care-giver stress and improve quality of patient care.

An approach he takes is to have the caregivers keep a jour-nal documenting the times and circumstances of the aggres-sion or agitation. This journal can help determine the cause.

Medical problems can include pain or possibly an infec-tion such as a urinary tract infection (UTI). Dr. Gallagher saidUTIs can make the general population agitated but it is evenmore difficult for dementia patients because “they are muchmore vulnerable to any change in their environment.”

“All the guidelines advocate non-medication approachesinitially and when you use medication you also use it in tan-dem with common sense, environmental, and caregiver strate-gies, and attending to unmet needs,” said Dr. Gallagher.

“When a pharmacological treatment is required there aregoing to be other first line treatments that are going to beused ahead of AEDs, but really the evidence base for thesetreatments is very small and we need further studies aboutnewer agents.”

—Find more info at http://ow.ly/DtU6E

Non-proprietary and brand names of therapies:car bamazepine (Tegretol, Novartis Pharmaceuticals Canada Inc.);valproate (Depakene, Abbott laboratories limited); levetiracetam(Keppra, UCB Canada Inc.); oxcarbazepine (Trileptal, NovartisPharmaceuticals Canada Inc.); gabapentin (Neurontin, Pfizer);topiramate (Topamax, Janssen); lamotrigine (lamictal,glaxoSmithKline).

AED possible treatment for agitation, aggression in dementia—Continued from page 1



THE WORLD HEALTH ORGANIZATION (WHO) andAlzheimer’s Disease International (ADI) issued a Junereport that contained a serious warning about the signif-

icant risk of dementia associated with smoking. The organi-zations joined forces to review the medical evidence regard-ing the relationship between tobacco use and dementia.

“This is a bold step,” said Dr. Peter Selby, chief of theAddictions Program and clinician scientist at the Centre forAddiction and Mental Health in Toronto. “It’s particularlyimportant for WHO to put out this report.”

After a review of numerous studies,WHO and ADI warn that smokers have a45% greater risk of developing dementiathan non-smokers and that 14% ofAlzheimer’s disease cases can potentiallybe attributed to smoking.

“A lot of people do not make the asso-ciation between smoking and dementia,[while] they make the association betweensmoking and heart disease and lung can-

cer,” said Dr. Selby, a professor in the Departments of Familyand Community Medicine and Psychiatry and the Dallan LanSchool of Public Health at the University of Toronto.

The report stated that the worldwide costs of dementia wereestimated at $604 billion in 2010. The two societies recommend-ed numerous measures in light of the strong link between smok-ing and dementia such as labelling of tobacco products to includethe risk of dementia, mass media campaigns informing the pub-lic of the link, and raising taxes on tobacco products.

NO CURES, SO MUST FOCUS ON MODIFIABLE RISK FACTORSThe report went on to say that with no cures for dementia northerapies available that can significantly alter the course ofdementia, developing strategies to address modifiable risk fac-tors like smoking to prevent, delay onset, or reduce the bur-den of dementia is imperative. Other modifiable risk factorsthat were cited included physical inactivity, hypertension, obe-sity, and diabetes.

When individuals have genetic risk factors for dementia,such as the apolipoprotein e4 allele, smoking can heighten therisk for carriers of this gene, according to the report.

The document discussed exposure to second-handsmoke and its impact on dementia. The researchers cited onestudy that examined dementia severity prior to diagnosis andfound exposure to second-hand smoke significantly elevatedthe risk for severe dementia syndrome. The risk was related toduration and frequency of exposure to second-hand smoke(Epidemiology July 2013; 24(4):623-624).

As dementia becomes more prevalent across the globe,public health specialists are examining modifiable risk factors asa measure to decrease the risk of dementia, explained Dr. Selby.

DEMENTIA PATIENTS WHO SMOKE MAY BE MORE AGITATEDIf patients already have dementia or mild cognitive impair-ment, smoking hastens the decline of their vascular health,explained Dr. Selby.

“[Smoking] is accelerating progression of disease,” hesaid. “It is worsening the prognosis for people with estab-lished dementia.”

Smoking also contributes to agitation in patients with

dementia, added Dr. Selby. “If they are not smoking, it helpsthem to be calmer and less irritable,” he said.

Healthcare professionals, no matter what their focus,need to pay attention to behaviours like smoking, said Dr.Selby. “No matter where you are coming from in medicine,this [smoking and dementia link] is relevant whether you workon mild cognitive impairment or the prevention of dementia.”

The report debunks the myth that there is a safe level ofexposure to tobacco smoke, said Dr. Selby. “These [findings]point out that any exposure is harmful, including second-handsmoke,” said Dr. Selby. “There is a dose-dependent relationship.”

In practical terms, individuals who have dementia andsmoke may start fires, explained Dr. Selby, noting thatthere have been incidents of individuals with dementiawho have unintentionally started fires in nursing homes asa result of smoking.

“People with dementia [who smoke] are at risk of sus-taining injuries [through a burn] and starting fires,” said Dr.Selby. “Even if a nursing home is smoke free, there is the con-cern that a resident who has dementia may wander off if theysmoke outside.”

NEED RESEARCH ON TIMING OF SMOKING CESSATIONThe report called for further study to look at the timing ofsmoking cessation in the lifespan and how the impact of ces-sation will lessen the risk of dementia.

“There is a benefit to quitting at any age,” said Dr. Selby.“Even if you quit smoking after the age of 60, you can gainthree years of quality-adjusted life years.”

A key benefit of this report is that it clarifies any conflict-ing evidence of the association between smoking and demen-tia, said Dr. Selby. The report cited several studies, which putforth that tobacco use was protective against dementia.Authors referred to the “The Health Consequences ofSmoking—50 Years of Progress,” 2014 U.S. Surgeon GeneralReport, which pointed to evidence that the tobacco industryinfluenced many epidemiologic studies of smoking.

—Find more info at http://ow.ly/DtUsz

WHO links dementia to tobacco use and second-hand smoken Without a cure for dementia physicians focus on modifiable risks such as smoking cessation

Dr. Selby

December 2014 n 11

C l i n i c a l T r i a l s

n Dementia patients 70 years of age andolder scheduled to undergo urology,orthopediatic, or general surgery arebeing sought for a trial. The purposeof the study is to examine if patientswho receive spinal anesthesia dur-ing surgery are less likely to devel-op Alzheimer’s disease two yearspost surgery than those individualsgiven inhalation anesthesia. Theinvestigators will also test allpatients for the presence ofapolipoprotein (Apoe-Îµ4 gene thatis present in 15% to 20% ofpatients), and beta-amyloid tau pro-tein (present in cerebrospinal fluid)that are known risk factors forAlzheimer’s disease. Interestedpatients can be advised to contactDr. george Djaiani at 416-340-4800ext 6205 or by e-mail at [email protected] or Jo Carroll at 416-340-4800 ext 3243 [email protected].

—More info is available athttp://ow.ly/F00ws

n Investigators are seeking adults aged55 to 90 years with a probableAlzheimer’s disease (AD) diagnosisfor a study to test if solanezumab willslow the cognitive and functionaldecline of AD compared to placebo.one arm of the study will receivesolanezumab 400 mg every fourweeks for 18 months and the otherwith receive placebo for the sameperiod of time. Contact the studydirector by phone at 1-877-285-4559or 1-317-615-4559

—More info is available athttp://ow.ly/F01Bo

n People aged 55 to 85 years with aclinical diagnosis of dementia due toprobable AD are being asked to par-ticipate in a study to test the safetyand efficacy of two fixed doses ofeVP-6124 for 26 weeks. Partici -pants will be randomized to threedifferent arms of the study. onegroup of patients will receive a lowdose tablet once daily, the othergroup a high dose tablet once daily,and the last group will receive place-bo once daily. Contact Sophieguillaume at 617-374-5705 or [email protected]

—More details at http://ow.ly/F02N3

Morguefile


By Louise Gagnon,Correspondent, The Chronicle

CANADA AND THE UNITED STATEShave the highest levels of pre-scription opioid consumption in

the world, according a study pub-lished in Sept. 2014 by the College ofFamily Physicians of Canada (CanFam Physician 2014; 60(9):826-832).

The study highlighted whatmany clinicians in Canada and theU.S. have called a public health epi-demic, describing rampant opioidprescribing and the escalation ofdoses when patients no longer areobtaining pain relief from opioids.Furthermore, there is concern aboutthe growing number of deaths caused by the opioids.

The authors reported that, on average, more than30 million tablets or patches of high-dose opioids were

dispensed in Canada yearlybetween 2006 and 2011 inclusive.They described a disparity in opi-oid prescribing across Canada, not-ing a three-fold provincial variationin the per capita rate of prescribinghigh-dose opioids. The researchersstated that their findings indicate aneed to consider developing anational strategy to address opioid

prescriptions.“The most important action that can be taken to

address this epidemic is for doctors to prescribe thesedrugs—and escalate doses—much less readily than wehave for the past 20 years,” said co-author of the paperDr. David Juurlink, a professor and head of the divi-sion of Clinical Pharmacology and Toxicology atSunnybrook Health Sciences Centre in Toronto.

In addition to the problem of patients developingopioid dependence and, in some cases, addiction, thewidespread prescribing of opioids for long-term use hasseen the growth of an underground use of opioids andthe illegal buying and selling of the medicines in Canadaand the U.S., noted Dr. Juurlink, who is also a medical

toxicologist at the Ontario PoisonCentre at the Hospital for SickChildren in Toronto.

The shift in clinical practicetoward the prescribing of opioids forextended periods is a practice that Dr.Juurlink and many others have criti-cized, because there are no good stud-ies documenting that the benefits ofthe practice outweigh the risks.

“There really is no good evi-dence for the use of these drugslong-term, and we are learning a greatdeal about the dangers of the prac-tice,” said Dr. Juurlink. “Most studiesof opioids last 12 to 16 weeks induration, are conducted in carefully

selected patients, and compare opioids to placebo.Not a single study has been done to ask whetherpatients on long-term opioids fare better than theymight have on other pain medicines, some of whichare safer than opioids.”

The U.S. is also acknowledging the high prevalenceof opioid prescribing and the American Academy ofNeurology (AAN), in the same month as the College ofFamily Physicians of Canada, released a position state-ment on opioids for chronic non-cancer pain (NeurologySept. 30, 2014; 83(14):1277-1284).

The AAN position paper notes that more than100,000 people have died in the U.S. since the shifttoward more liberal opi-

12 n December 2014

OxyNEO in 2012, which was claimed to be more difficult to abuse, occurredamid controversies that the reason for introducing the new formulation wasmerely to compensate for the expiration of the Oxycontin patent.9 It also cor-responded to a surge in heroin use among communities in Ontario10 whileways were found to misuse the new formulation. Some reports went as far asto claim the attempts to curtail Oxycontin resulted in an undermining of pub-lic health and safety in Ontario.11

Canada’s Minister of Health, Rona Ambrose, is making a call to physiciansto reduce opioid prescriptions, the Globe and Mail has reported.12 However theminister’s call is a unidimensional approach hoping to reduce availability of pre-scription opioids without consideration of alternative treatment strategies (asdescribed earlier), centralized drug monitoring services, treating current patientson long-term opioids and understanding the nature of opioid addiction.

We will not see improvements with respect to this opioid epidemic withoutthe involvement of health, law, and social systems. These areas need to worktogether to create an integrated evidence-based solution and collaborative caremodel for patients with chronic pain and addiction disorders.

REFERENCES1. INCB, INCB: Report of the International Narcotics Control Board for 2010

(E/INCB/2010/1) 2010.2. Webster PC: Medically induced opioid addiction reaching alarming levels.

CMAJ 2012; 184(3):285-286.3. CDC, CDC: National Vital Statistics System. http://wonder.cdc.gov, 2011.4. Gomes T, et al: Trends in high-dose opioid prescribing in Canada. Can Fam

Physician 2014; 60(9):826-832.5. Dhalla IA, et al: Prescribing of opioid analgesics and related mortality before

and after the introduction of long-acting oxycodone. CMAJ 2009;181(12):891-896.

6. Franklin GM: Opioids for chronic noncancer pain: a position paper of theAmerican Academy of Neurology. Neurology 2014; 83(14):1277-1284.

7. Samaan Z, et al: Genetic influence on methadone treatment outcomes inpatients undergoing methadone maintenance treatment for opioid addic-tion: a pilot study. Neuropsychiatr Dis Treat 2014; 10:1503-1508.

8. Dennis B, et al: Evaluation of clinical and inflammatory profile in opioidaddiction patients with comorbid pain: results from a multicenter investiga-tion. Journal of Neuropsychiatric Disease and Treatment 2014. in press.

9. Fletcher J, Tsuyuki RT: Don’t tamper with oxycodone. Can Pharm J (Ott)2013; 146(1):6.

10. Ogilvie M: OxyContin replaced by explosion of small-town heroin use, inThe Star. Aug. 17, 2012.

11. King S: OxyContin in Ontario: the multiple materialities of prescriptionpainkillers. Int J Drug Policy 2014; 25(3):486-493.

12. No magic pill solutions in Rona Ambrose’s crusade against opioids. TheGlobe and Mail; Oct. 6, 2014.

—Continued from page 3


Wikim

edia Com

mons

Multi-dimensional approach needed to address opioid epidemic in Canada

Reports suggest physicians over-prescribe

opioids

Dr. Juurlink


December 2014 n 13

by Emily Innes,Assistant Editor, The Chronicle

SOCIAL MEDIA CAN BLUR THE BOUNDARIESbetween personal and professional identi-ties for health care providers. Furthermore,

there are situations regarding professionalism,confidentiality, and privacy that may be uniqueto psychiatry, according to a presentation at theCanadian Psychiatric Association’s 64th AnnualMeeting in Toronto.

The presentation “#Blurred Lines:Challenges Encountered by Psychiatry Traineesand Psychiatrist in Maintaining Professionalismin the Digital Age,” was given by fifth-year resi-dents in psychiatry from the University of Toronto, Dr.Kathleen Sheehan and Dr. Jennifer Laidlaw, together withstaff psychiatrist and assistant professor, Dr. Adrienne Tan.

Dr. Sheehan, in introducing the topic, indicated thatguidelines are available regarding the professional use of

social media, but that guidelines alone arenot sufficient.

“When we think about the guide-lines, and why we think this is such ablurry topic, we have to think about howhelpful they are in actually guiding whatwe do online and the discussions that wehave,” said Dr. Sheehan. “Really how wefeel is that they are necessary, but theyare not sufficient. Because while they

provide examples they do not really provide clear examplesof what is OK and what is not OK.”

The guidelines Dr. Sheehan addressed highlighted theCanadian Medical Association—Social Media and CanadianPhysicians (2012), the Canadian Medical ProtectiveAssociation’s Privacy and Confidentiality statement on pro-tecting patient information, The College of Physicians andSurgeons of Ontario’s guidelines (Dialogue 2013; 2:30-32), andThe Canadian Federation of Medical Students’ Guide toMedical Professionalism: Recommendation for Social Media(2013). Dr. Sheehan mentioned that most medical schools andhospitals have their own social media guidelines and thereforephysicians are responsible for meeting several sets of guide-lines simultaneously.

“The common principles [of the guidelines] are really thatconfidentiality is key. Social media should always be consideredpublic and permanent . . . Just like people can figure out who [Mr.X is], even though you do not use names when you are talkingabout Mr. X in the elevator with someone, patients can triangu-late information online as well. Identifiable patient informationshould not be posted,” said Dr. Sheehan. The posting of identi-fiable patient information online can have professional and/orlegal consequences.

The various guidelines, summarized by Dr. Sheehan, alsorecommend that privacy settings should be high when usingthe sites for personal use. However, physicians should com-port themselves with the same high standards of profession-alism that would govern face-to-face interactions, regardlessof privacy settings.

“I think most people have the sense that if I saw Mr. Xin the emergency room about his bipolar mania, most of ushave the sense that [posting about him by name] goes too far,”said Dr. Sheehan about the examples provided in previouslylisted guidelines. “But, there is this grey area where the realcomplexities of what is happening [such as] when your patientfinds out something about you or you have to make a decisionabout whether you are going to look up a patient online.

Those types of clinical scenarios that are quite nuanced arenot really discussed in the guidelines. I think [they] are diffi-cult for us to discuss with supervisors who sometimes do nothave a lot of experience in that area either.”

TERM PROFESSIONALISM IS CONTINUALLY REDEFINEDDr. Laidlaw said definitions for professionalism have beenaround for a long time in medicine and are continually

adapting. She referenced the MedicalProfessionalism in The New Millennium:A Physician Charter (Ann Intern Med 5Feb. 2002; 136(3)).

“Professionalism is the basis of medi-cine’s contract with society. It demandsplacing the interests of patients above thoseof the physician, setting and maintainingstandards of competence and integrity, andproviding expert advice to society on mat-

ters of health,” stated the authors of the MedicalProfessionalism in The New Millennium: A Physician Charter.

The charter preamble continues, “At present, the medicalprofession is confronted by an explosion of technology, chang-ing market forces, problems in health care delivery, bioterror-ism, and globalization. As a result, physicians find it increasing-ly difficult to meet their responsibilities to patients and society.In these circumstances, reaffirming the fundamental and uni-versal principles and values of medical professionalism, whichremain ideals to be pursued by all physicians, becomes all themore important.”

SOCIAL MEDIA CHANGES TEACHER/STUDENT RELATIONSHIPDr. Tan said with the potentially blurred lines between per-sonal and professional id16entity, there can be tension between the best interest of thepatient and the physicians entitlement for a personal identi-ty outside of their professional one.

“We have a right to air our grievances. [The dilemma is] thatI am a person and I have a right to express myself, versus I have

to live up to a higher standard because ofthe career that we have chosen and thesocial responsibility it entails,” said Dr. Tan.

Dr. Tan said a great divide nowoccurs between the experiences of differ-ent generations with social media, oftenwith the teachers being at a disadvantage.

“[In] the traditional paradigm, theteacher has the power and authoritybecause of knowledge [but social

media]turns that on its head because we do not have that[knowledge], our learners have that,” said Dr. Tan. “We canturn it around and say ‘I’m a teacher and I can guide youthrough this process but I do not have content expertise onthis, I am learning with you on this’.”

Grey areas of medical professionalism on social median Psychiatrists discuss #blurred lines of professionalism on Twitter, Facebook at annual CPA meeting

Dr. Tan

Dr. Sheehan

Dr. Laidlaw

M e e t i n g s

Jan. 16-18, 2015Professional Society of ADhD andrelated Disorders Annual Meeting:

ADhD and related Disorders: State ofthe Science & ArtWashington

Contact: RegistrationE-mail: [email protected]: 615-649-3083

Website:http://www.apsard.org/meeting/

Jan. 17, 2015The Canadian Sports Association

Concussion Project 3rd AnnualSymposium Toronto

Contact: RegistrationE-mail: [email protected]: http://ow.ly/EZNd3

Mar. 1-4, 201519th Annual Children’s

Neuroscience SymposiumPhoenix

Contact: Christina CasanovaPhone: 602-933-0923

E-mail: [email protected]

Mar. 18-22, 2015The 12th International Conference on

Alzheimer’s and Parkinson’s DiseasesNice, France

Contact: RegistrationPhone: 41-22-908-0488E-mail: [email protected]

Website: http://ow.ly/wkMK8

Mar. 22-25, 20156th World Congress on Women’s Mental health

TokyoContact: Congress SecretariatPhone:81-3-5216-5318

E-mail: [email protected]:

http://www.congre.co.jp/iawmh2015

May 16-20, 2015American Psychiatric Association

168th Annual MeetingToronto

Contact: RegistrationPhone: 1-703-907-7300

E-mail: [email protected]

June 9-12, 2015Canadian Neurological Sciences

Federation 50th CongressToronto

Contact: RegistrationE-mail:

[email protected]: http://congress.cnsfedera-

tion.org/

Gerardo O

bieta, Flickr


MTHFR deficiency as cause of HSP lead to treatmentfamilies who presented with similar progressive spasticparaparesis and polyneuropathy, which was variably associ-ated with behavioural changes, cognitive impairment, psy-chosis, seizures, and leukoencephalopathy. Symptoms hadfirst emerged between the ages of 29 and 50 years, and bythe time they were diagnosed a decade later, one of the fourwas bedridden.

Paraparesis usually develops late in MTHFR deficiencyand is preceded by cognitive, behavioural, or psychiatric man-ifestations, which contrasts with what is expected in HSP, saysDr. David S. Rosenblatt, a professor in the Departments ofHuman Genetics, Medicine, Pediatrics, and Biology at McGill

University, who co-authored the research.The seizures, behavioural regression, slowcognitive deterioration or psychosis thatthree of the patients presented with wasan important clue to the correct diagnosis,he says.

There had been three patients of sim-ilar age at onset with MTHFR deficiencyreported in the literature, says Dr.Rosenblatt, but none had a family history

of HSP. All had periods of rapid deterioration (not observedin the patients studied in this paper) on top of the character-istic slow progression of MTHFR deficiency.

Investigations of the four patients found both severehyperhomocysteinemia and hypomethioninemia, andfibroblast MTHFR enzyme activity 18% to 52% below con-trol participants. Three novel pathogenic MTHFR muta-tions were identified, including two in one family as com-

pound heterozygotes and a homozygous mutation in theother family.

Demyelination as in sub-acute combined degenerationunderlies the neurologic findings in severe MTHFR deficien-cy, says Dr. Rosenblatt. This is probably caused by low methio-nine and S-adenosylmethionine, likely resulting in the kind ofpredominantly posterior-periventricular distributed leukoen-cephalopathy seen in the four studied patients, and may some-times reverse with treatment, he says.

“The clear findings of both mutations and decreasedactivity of the [MTHFR] enzyme” led doctors to connectthe deficiency to the patients’ spastic symptoms, says Dr.Rosenblatt.

TREATMENT WITH BETAINE RESULTED IN IMPROVEMENTThe four patients were treated with betaine, and all four had arapid, 50% to 70% decline in homocysteine. Treatment result-ed in an improvement in the condition of the three ambulato-ry patients over a period of nine to 15 years.

Practitioners should “consider the diagnosis of severeMTHFR deficiency and measure levels of total homocysteinein the blood of patients” with late-developing parapareisis inHSP, says Dr. Rosenblatt.

“Because patients respond to therapy with betaine, thereis the possibility of treatment,” for certain types of HSP forthe first time, says Dr. Rosenblatt.

The findings of a potentially treatable metabolic cause ofHSP suggests a possible direction for future research into pos-sible treatment angles for some types of HSP, says Dr.Rosenblatt. “Particularly when there is more than one case ina sibship, the possibility of a genetic disorder should be con-sidered,” he says.”

Dr.Rosenblatt

14 n December 2014

The eDIBle oIl TrIhePTANoIN hAS SIgNIFICANTlY reduced seizuresfor patients with the metabolic disorder glucose transporter typedeficiency 1 (g1D) in a small sample, according to a studypublished in the journal JAMA Neurology (oct. 2014;71(10):1255-1265).

The oil derived from castor beans appeared to amelioratethe brain glucose-depletion associated with this genetic disorderand the 14 pediatric and adult patients in the study showed signsof rapid increase in brain metabolism and improved neuropsy-chological performance.

“This study paves the way for a medical food designationfor triheptanoin, thus significantly expanding therapeutic optionsfor many patients,” stated Dr. Juan Pascual, associate professorof Neurology and Neurotherapeutics, Physiology, and Pediatricsat UT Southwestern Medical Centre in Dallas and lead author ofthe study, in a press release.

The only proven treatment for g1D has been a high-fatketogenic diet, which only works for about two-thirds of patients.

OIL POTENTIALLY AS EFFICIENT AS KETOGENIC DIETBased on the results of this trial, triheptanoin appears to work asefficiently as the ketogenic diet; however, more research needsto be done before the oil is made available as a medical foodtherapy, researchers said.

“Triheptanoin byproducts produced in the liver and also inthe brain refill brain chemicals that we found are preferentially

diminished in the disorder, and this effect is precisely whatdefines a medical food rather than a drug,” said Dr. Pascual.

The oil, approved for use in research only in the U.S., is aningredient in some cosmetic products and is added to butter insome european countries.

Dr. Pascual plans to do further research to refine the opti-mal dosage toward the goal of facilitating medical food designa-tion of triheptanoin as a new g1D treatment.

—Read more information at http://ow.ly/F3a6m


Edibile oil promising treatment option for Glut 1 deficiency

Dr. Juan Pascual, an associate professor of Neurology andNeurotherapeutics, Physiology, and Pediatrics at UT SouthwesternMedical Centre in Dallas with a six-year patient who participated in histrial looking at the efficacy and safety of triheptanoin oil as a treatmentfor glut 1 deficiency.


by John Evans,Assistant Editor, The Chronicle

AN INVESTIGATION OF ADULTS ENROLLED in theQuebec Adipose Lifestyle IntervenTion in Youth(QUALITY) study has found that symptoms of

the eating disorder night eating syndrome (NES)—assessed by the Night Eating Questionnaire (NEQ)—are associated with both poorer metabolic health andhigher BMI, according to findings published in EatingBehaviors (Apr. 2014; 15(2):186-191).

The principle investigator on the NES project inQUALITY is Dr. Vicky Drapeau, associate professorand researcher in the Department of Physical

Education at Laval University. Co-investigator of the project is Dr.Lungren from the Department ofPsychology of the University ofMissouri—Kansas City

“Dr. Drapeau initiated thisproject after meeting with Dr.Albert Stunkard [of the PerelmanSchool of Medicine at theUniversity of Pennsylvania], a psy-

chiatrist and researcher, who first published on nighteating syndrome,” says study co-author Annette Gallant,PhD, who also researches eating-related risk factors atLaval. “The subject struck a chord with Dr. Drapeau,who, as a researcher and nutritionist, saw patients withrelated symptoms.” Dr. Gallant says that NES fit wellwith the team’s research interests due to its atypical dailyeating patterns and altered sensations of appetite.

NO PRIOR CANADIAN STUDIES LOOKING AT NESWhen the study was initiated, no Canadian studies hadfocused on NES, says Dr. Gallant. “Furthermore, therewere important gaps in the NES scientific literature.There lacked studies in children, prospective studies,and studies that examined the association between NESand metabolic disease. Researching NES seemed like anatural next step for our team,” she says.

Other researchers have looked at night eating syn-drome and a possible connection to metabolic problems,says Dr. Allan Kaplan, vice chair of research, director ofthe Clinician Scientist Program and professor of psychi-

atry at The University of Toronto,who has focused his research on thepsychobiology of eating disorders.Though he says the research has notbeen as rigorous as he would hope,“[This condition] needs moreresearch, and [Dr. Drapeau and col-leagues] comment on that, especiallycorrelating it with some of the neu-ropeptides that they talk about; gre-

lin, leptin, [neuro-peptides] like that.”The cross-sectional nature of the study limits

what can be said about the findings, says Dr. Kaplan,which is particularly a problem when measuring com-ponents like neuropeptides, which are very reactive tothe environment.

“They react to environmental stressors or cues,such as eating or not eating, sleeping or not sleeping.You would have to do repeated measures of those hor-mones to get a sense of what is going on, how disrupt-ed they are. One of the points [the authors] make is thatthe circadian rhythm of these hormones is disrupted.That is not that surprising, because they are very sensi-tive to sleep, and light, and eating behaviour. You wouldbe surprised if they were not disrupted.”

A total of 310 women with a mean age of40.3±5.1 years, with a mean BMI of 28.8±6.2 kg/m2,and 305 men with a mean age of 42.5±5.9 years, andmean BMI of 30.3±5.0 kg/m2 from the QUALITYcohort had their night eating symptoms assessed.Anthropometric measures, fasting blood samples, andblood pressure were used to diagnose metabolic syn-drome (MetS). Patient self-report data was used to diag-nose type 2 diabetes. Eating behaviours were alsorecorded through patient self-reporting.

The QUALITY cohort was used, Dr. Gallant says,because it was a “prospective design and it has a rich dataset of measured cardiometabolic variables.” The cohortincluded children aged eight to 10 years, who had at leastone obese parent. “This is an important feature of thecohort because the prevalence of NES is greater inobese populations. Because of these cohort characteris-tics, we felt our team would be able to explore several of

the gaps in the current literature,” she says.Morning anorexia was found to be associated with

MetS diagnosis in both genders, but urges to eat at nightwere only associated with MetS diagnosis in women. Apositive correlation was also found between NEQscores and BMI, and when BMI was controlled for,NEQ scores were significantly negatively correlatedwith blood pressure in women, and positively correlatedwith both waist circumference and triglycerides in men.

“I think what is important, which is a huge pub-lic health issue, is the increasing prevalence of obesi-ty,” says Dr. Kaplan, when asked about the take awaymessage of Dr. Drapeau and her colleagues’ research.“Obesity is a final common pathway for a lot ofbehaviours, one of

Dr. Drapeau

Dr. Kaplan

December 2014 n 15

Night eating syndrome associated with poor metabolic health, higher BMIn Study provides evidence that it is important to screen obese patients and those with metabolic disorders for night eating syndrome

have a cognitive emotional bias toward negative emotional stimuli in the environment,” explained Dr.McIntyre. “This interferes with their functioning.”

Major depressive disorder is not necessarily a progressive disorder, but in about half of patients who presentwith a first episode of depression, they will go on to have repeat episodes of depression, said Dr. McIntyre.

“These are the majority of people who we continue to see,” he said. It’s these patients who are facing aheightened risk of developing Alzheimer’s disease in later life, explained Dr. McIntyre. One case register studyfound that the risk of dementia appeared to rise with the number of episodes in depressive and bipolar affectivedisorders (J Neuro Neurosurg Psychiatry Dec. 2004; 75(12):1662-1666).

The relationship between major depression and Alzheimer’s disease is related to the role of amyloid betain the brain. One investigation looked at cerebrospinal fluid levels of amyloid beta, tau protein, and F2-iso-prostanes in depressed individuals and control subjects, with investigators finding amyloid beta 42 levels beingsignificantly decreased in patients with major depression (Am J Psychiatry May 2012; 169(5):523-530).

The challenge in clinical practice is not initiating anti-depressant therapy, but optimizing that thera-py, he explained.

According to Dr. McIntyre, optimizing therapy for major depressive disorder can be achieved throughtitration of the dosage of medication, such as a selective serotonin reuptake inhibitor or selective norepi-nephrine reuptake inhibitor, or augmenting the initial choice of medication, an anti-depressant, with anoth-er therapy, such as an atypical antipsychotic—quetiapine or aripiprazole.

Unfortunately, patients who are not naive to antidepressant pharmacotherapy are unlikely to experiencetreatment success with alternative pharmacological agents down the road, said Dr. McIntyre.

While it is not a popular option among patients for treating depression, electroconvulsive therapy is aneffective modality. Various forms of psychotherapy such as cognitive behavioural therapy should also be con-sidered as a treatment option for patients with major depressive disorder.

Non-proprietary and brand names of therapies: quetiapine (Seroquel, AstraZeneca Canada Inc.); aripiprazole(Abilify, Bristol-Myers Squibb Canada).

Optimize antidepressant to avoid weight gain—Continued from page 7


Morguefile


Opioids: management of chronic pain needs to be tailored to the individual

Evidence that night eating disorder, BMI or metabolic health is linked to obesity

oid use, dating from 1999 to 2010.“You do not have to be on [opioids] very long to

become dependent,” said AAN paper author Dr. GaryFranklin, a research professor in the Department ofEnvironmental and Occupational Health SciencesMedicine (Neurology) and Health Services at theUniversity of Washington and the medical director ofthe Washington State Department of Labor andIndustries in Seattle.

Dr. Franklin recommended that clinicians first con-sider prescribing non-pharmacologic alternatives to opi-oids for pain management in chronic non-cancer pain,

such as physical therapy and cogni-tive behavioural therapy.

Canadian psychiatrists andphysicians who are addiction expertsare taking action to reduce the highlevels of opioid prescribing, whichwas a topic of discussion during the2014 Annual Conference ofRehabilitation Medicine (ACRM)held in Toronto in October.

Dr. Peter Selby, chief of the Addictions Division atthe Centre for Addiction and Mental Health and a pro-fessor in the Departments of Family and CommunityMedicine, Psychiatry and Public Health Sciences at theUniversity of Toronto, suggested that to help curtail thesignificant social problem of illegal exchange of opioidsand to avoid the potential for addiction in patients, judi-cious prescribing is in order.

Prescriptions should be limited to 10 days,requiring patients to visit physicians for refill pre-scriptions, and shorter durations should even be con-sidered in some instances, suggested Dr. Selby.

“We can even look at daily dis-pensing of an opioid,” said Dr.Selby, who spoke during theACRM’s 91st conference.“Information about the risk ofdependence on opioids should becommunicated before we write thefirst prescription.”

Clinicians should request urinesamples at every patient visit if there

is long-term opioid prescription to ensure patients aretaking prescribed opioids, and to check for the presenceof any other substances that might interact with opioids,such as benzodiazepines, cocaine, etc. These practices will

also serve to reduce the supply of opioids available to besold illegally, advised Dr. Selby.

IMPORTANT TO MONITOR HISTORY OF ADDICTIONAnother factor compounding the issue of addiction isthat a significant proportion of patients who are beingprescribed opioids may present with a prior history ofaddiction to alcohol or substances. Of patients with ahistory of addiction to alcohol or substances, 30%experience traumatic brain injury, noted Dr. Selby.

Apart from the potential for addiction, clinicianshave to consider other possible adverse effects associ-ated with long-term opioid use such as hypogonadismand osteoporosis, said Dr. Selby.

During the meeting, Dr. John Flannery, a physiatristand the medical director of the MusculoskeletalRehabilitation Program at the Toronto RehabFoundation, part of the University Health Network,

called for a revised approach tochronic pain management that seesopioids as “one component” of painmanagement and not the panacea forpain management.

Dr. Flannery and colleaguesoffer multi-disciplinary care topatients with chronic non-cancer painand aim to decrease pain scores by30%, a modification in score that can

result in a meaningful change in daily living.“The difference in pain can mean that patients can

now get dressed and brush their hair, for example,” saidDr. Flannery. “We have to find out what their goals are.”

MUST MANAGE PATIENTS EXPECTATIONS FOR PAIN TxDr. Andrea Furlan, an associate professor in theDepartment of Medicine at the University of Toronto,staff physician and scientist at the TorontoRehabilitation Institute, and co-author of the CanadianGuideline for Safe and Effective Use of Opioids forChronic Non-Cancer Pain issued in 2010, said a com-prehensive assessment of a patient’s needs should beconducted before opioid therapy is initiated, in con-junction with adequate communication with a patientto manage their expectations of pain treatments.

The guideline presented more figures about howmore patients are being prescribed opioids and in larg-er doses. In Ontario, for example, oxycodone prescrip-tions rose by 850% from 1991 to 2007, to 197 per 1,000individuals per year from 23 prescriptions per 1,000individuals per year. In addition, the average amountper prescription of long-acting oxycodone increased to

2,280 mg from 1,830 mg.“Patients come to see us with expectations that

they can alter their situation, so they will have no pain,”said Dr. Furlan. “Many patients are chasing a target thatis not achievable.”

Dr. Furlan said more realistic expectations need tobe set for patients with chronic non-cancer pain. Thefirst expectation they need to recognize is that theirpain will never completely go away.

The key lies in having effective communication withpatients, so that they have a realization that chronic painis part of their new reality, and that opioids are “onetool” aimed at improving their day-to-day function,explained Dr. Furlan. The appropriate dose of opioidshould be matched to the patient’s functional goals.

“If a patient is able to get back towork and take care of his or her chil-dren, [then the dose is appropriate forthat patient],” explained Dr. Furlan.

Conversely, if the dose of opi-oid continues to be titrated andthere is no functional benefitderived for a patient, the dose esca-lation should cease and cliniciansmay consider cessation of opioid

therapy altogether, said Dr. Furlan.Part of proper screening before initiating opioid

therapy is identifying any pre-existing depression,warns Dr. Furlan.

“We do not know what effect the opioid will have[if the patient already has depression],” said Dr. Furlan,noting she uses the Patient Health Questionnaire-9 toscreen for major depressive disorder in patients beforeinitiating opioid therapy. “The patient can develop dys-phoria [while on an opioid], but the patient can alsodevelop euphoria and that would mask the depression.”

Depression would need to first effectively be man-aged, ensuring that the patient is stable before opioidtherapy is initiated, according to Dr. Furlan.

As with other medical conditions, management ofchronic pain needs to be personalized and tailored to theindividual. “Pain is subjective, and we understand chron-ic pain is not the same for everyone,” said Dr. Furlan.

To assist physicians, Dr. Furlan helped to developthe Opioid Manager, a sheet that contains critical infor-mation from the 2010 Canadian guideline on using opi-oids. The tool is available in numerous electronic medicalrecord platforms and as an app for iPad/iPhone devices(www.opioidmanager.com).


Dr. Flannery

Dr. Selby

Dr. FranklinDr. Furlan

which might be night eating syndrome. And obesity leads you down a wholebunch of other paths that impact on health.”

While this study is cross-sectional, and so cannot identify a causal direction betweensleep eating disorder and BMI or metabolic health, Dr. Kaplan says “it adds to the evi-dence that practitioners need to be aware that obesity is a final common pathway. It isnot one distinct entity. So in the assessment of someone who is obese, you want to askabout their sleep patterns, and you want to ask about their eating behaviour.”

The study is also limited for not controlling for other conditions that impact eat-ing and sleep, such as depression, says Dr. Kaplan. “If you do not control for that,you do not know what is causing what. People who are depressed do not sleep verywell. Once they have a sleep problem, does that then trigger them getting up and eat-ing?”

The team is continuing to track their cohort in the hopes of collecting some lon-gitudinal data. “We are currently investigating the association between baseline night

eating symptoms and two-year weight change in adults,” says Dr. Gallant. “We alsoaim to explore changes in night eating symptoms across time and how these changesare implicated in metabolic health.

OBESE, METABOLIC DISORDERS PATIENTS SHOULD BE ASKED ABOUT NES“Obesity and metabolic disease are complex health problems with a multifactoral eti-ology,” says Dr. Gallant. With that in mind, the study findings suggest that patientsexhibiting weight and metabolic problems should be questioned about eating andsleep patterns, she says.

Dr. Kaplan agrees, noting that “when people come to a physician, they are pri-marily interested in weight loss. They do not know that maybe they have an abnor-mal metabolic profile. They may not even tell their practitioner they are getting up atnight to eat. Their focus is on their weight and their wish for weight loss. So mostpractitioners do not take the time—certainly in primary care—to evaluate it morefully. They will just make some recommendation for a low-calorie diet or will make areferral to a weight loss program, or something like that.”


16 n December 2014


MANY YEARS AGO, I LOOKED at clothing worn inNapoleonic times and realized that adults wereabout the size of our 12-year-olds. I was aware

of houses with four-foot doors in the oldEnglish town of Petworth, and this set methinking. Conventional wisdom was thatwe are larger because of better food, butthese aristocrats ate well and were still notlarger than the population.

The thought laid dormant until recent-ly, on noticing that my students, nephews,and nieces were significantly larger than mygeneration, even in comparison to theirparents. They are as different from us asour Philippine friends are from friends ofEuropean descent. I had not thought aboutevolution in Homo sapiens, certainly not ina way that was noticeable within my lifetime, yet here was an indisputable trend. Isit related to our being, in effect, in a larger‘fish tank’ now that we can travel easilyaround the whole planet?

So I began reading. Classical bookssuch as The Red Queen by Matthew Ridley,argue that we evolve to try to outpace theparallel evolution of infectious diseases,which was a good starting point. From scientific jour-nals, I discovered that maternal genes tend to encour-age smaller babies and those from the father, largerones. Clearly it is in the mothers’ interest to limitresources that go into producing each child, so she isable to produce more and has a better chance of theirreproducing. From the father’s perspective, the largerand better ‘fed’ the baby is at birth, the better its

chance of survival, and passing on his genes. I beganto look at genetic drift as an ongoing balancing act.

Furthermore, if people are evolving, how does evo-lution affect our brain? The incidence ofcertain mental health problems is chang-ing, not entirely due to changes in diag-nostic criteria, but because people’s atti-tudes are changing. We accept anapproach that emphasizes autonomy andsuccess, even at the expense of others, orfailure and being held personally respon-sible, which is very different from the1970s. Is this social change or a funda-mental difference in how we perceive oth-ers? Have our social groups become solarge that the genetic advantage of altru-ism has become negligible because ourgenetic commonalities are small? Do wegain more advantage by selfish acts, con-centrating only on our nuclear families?

Papers and articles on the psycho-pathic traits of the CEOs of large cor-porations, following the financial disas-ters of the past decade, led me to won-der if the relative frequency of genesfor narcissism and empathy had

altered. Clearly, being a socially functioning individualwith psychopathic tendencies has significant advan-tage, in the short run, overcommunity-minded andempathetic people whowould not harm others forpersonal gain.

Which brings me to this

book. The Psychopath Inside tells a gripping personal histo-ry; as a neuroscientist studying serial killers, [James]Fallon, PhD, discovers a pattern of brain activity that isdifferent from other prisoners and controls. Initially, thisis thought to reinforce his belief that they are, in effect,born that way, but then he discovers this pattern of brainactivity in a control subject. This was not, as he first sus-pected, due to misfiling, and when the code is broken itturns out to be none other than himself.

BOOK A HIGHLY THOUGHT PROVOKING READ The discovery leads to his uncovering a fascinating fam-ily history, and coming to terms with aspects of his ownpersonality, not appreciated by others, that stem fromwhat he realized is a relative lack of empathy even forfriends and family members. I suspect it is this emotion-al difference that enables him to write the book.

He decides to deliberately change what he does,even if he cannot change how he feels. Eventually hehas to admit that, despite his former beliefs, a child’senvironment is likely what determines the differencebetween those who commit heinous crimes and those,like himself, who are successful members of society.

His book is a highly thought provoking read,which leads into another set of questions: can we pre-vent psychopathy and possibly mental illness by theway we care for our preschoolers? But that is anotherstory. For now, anyone with an interest in how ourbrain affects behaviour should read this.

Publisher:Penguin Group USA

Book information: ThePsychopath Inside:

A Neuroscientist’s PersonalJourney Into the Dark Sideof the Brain, first pub-lished 2013, 256 pages.The purchase price isapproximately $30

Book review: ‘The Psychopath Inside’ a neurologist’s gripping storyn reviewer Dr. Pippa Moss says ‘The Psychopath Inside’ is an interesting read for anyone interested in how the brain affects behaviour

ABOUT THE REVIEWER

Dr. Pippa Moss is recognized by the Royal College of Physicians and Surgeons asa Founder of Child and Adolescent Psychiatry. Dr. Moss works in four health dis-tricts in Nova Scotia and also at The Hospital for Sick Children in Toronto. Sheis the project lead for a home for AIDs abandoned and orphaned children in Kenya.

1.888.647.7327 wwwwww..sseeaaccoouurrsseess..ccoomm

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18 n December 2014

Dr. Benoit Mulsant is physician-in-chief at Toronto’s Centrefor Addiction and Mental Health and a professor andvice-chair in the Department of Psychiatry at the

University of Toronto. For more than 20 years, Dr. Mulsanthas been studying mood disorders in elderly patients, which hehas observed as a risk factor for Alzheimer’s disease (AD).This led to an interest in studying ways to prevent dementia andrelated disorders in these patients. In April 2014, a proposalby Dr. Mulsant and his colleagues for a study of an interven-tion to prevent Alzheimer’s disease received nearly $10-millionin funding from the Brain Canada Foundation and theChagnon Family over five years. The PACt-MD (PreventingAlzheimer’s dementia with Cognitive remediation plus tDCS(transcranial direct current stimulation) in MCI (mild cognitiveimpairment) and Depression) study will look at 250 olderadults with clinical depression and 125 with MCI. The partici-pants will be randomly assigned to receive tDCS with cognitiveremediation or a control (“placebo”) intervention. THECHRONICLE’S Emily Innes spoke with Dr. Mulsant regardinghis innovative work.

What was it like to have PM Stephen Harper presentyou and your colleagues with the largest-ever grantfor Alzheimer’s disease prevention in Canada?It was very nice . . . It was an acknowledgement that theresearch we are doing is important to Canadians. We arevery excited to be able to actually do the work and try todevelop prevention for the disease. Like many researchprojects, not all succeed, but we are confident that if wedo not [succeed] with our main objective, we will be ableto learn more about cognitive remediation and brain stim-ulation in that population. [And] it is like any research,then you modify your design and you get at it again.

What is your main objective from the PACt-MD study?What we want to discover and learn is can this inter-vention prevent AD? Our hypothesis is that over fiveyears, we should be able to reduce the onset of AD(or other dementia) by 50 per cent—by half—in thegroup that gets the intervention.

In addition, we are going to use various bio-markers so we can look at the brain structure and

the genetics of the patient and try to understandbetter why some patients with depression and MCIdevelop dementia and why some do not. We will alsobe able, regardless of the outcome of the interven-tion, to address some of those important neuro-science questions.

How did you arrive at the decision to select the interventions tDCS and cognitive remediation?Dr. [Tarek] Rajji, other colleagues [and I] have [used]various protocols at CAMH, that offer brain stimula-tion-ECT (electroconvulsive therapy), rTMS (repetitivetranscranial magnetic stimulation), [or] DBS (deepbrain stimulation). tDCS is the one that is the mostnovel and the one the least used. It has the advantage ofbeing minimally invasive and requires [an] extremelyinexpensive device. You can buy a tDCS stimulator onthe Internet for as low as $70. By contrast, for DBS—the stimulator and the neurosurgery cost $150,000 perpatient. When we are talking about prevention [for] alarge group of people, tDCS is very attractive as brainstimulation.

Cognitive remediation is a form of retraining. Weknow that those [approaches] can be effective based onsmall studies. Both the tDCS and the cognitive remedi-ation have shown to be effective in small groups ofpatients over the short term.

That is what this study is about: can we combinethem to get a stronger and more durable effect? Ifthe trial is successful you can always go back and[ask], do you really need both? [But], here we want tomaximize powers.

How did you determine which patient population toinclude in this study?At this point we are taking two populations of patientswho are very high risk for AD and dementia. We aretaking people who have a condition called MCI, withwhich typically 10 to 15 per cent of patients developAD during each subsequent year. So, over five yearsmore than half of them would develop AD without anintervention.

And then we take older people who have recov-ered from a major depression. That group has alsoshown to be at very high risk for AD: half of themhave a pure depression, we expect that in the absenceof intervention it would be that 30 to 50 per cent ofthem would develop AD or a related dementia duringthe next five years. That is why this prevention studyfocuses on these two high risk groups.

The next step—if it works in the high riskgroups—would be to try it in the population that is atrisk based solely on age. For such a study, you wouldneed many more patients, you may need [1,000] or2,000 people for five years. [In our current study]because subjects are high risk we may be able todemonstrate the efficacy of the intervention with 375subjects.

Why do you think it is important for Canada to invest resources into AD and dementia research—specifically for prevention?It is because most of the treatments we have tried so farhave been tried when people are symptomatic and atthat point there is really too much brain damage to havean impact.

So the idea is to intervene earlier. Here we areintervening before the disease becomes symptomatic.We believe we have a much better chance to delay theonset or the progression of symptoms than what hasbeen done before.

The data shows that in Canada and all Western[countries] if we do not find a cure, AD and otherdementias are going to ‘break the bank.’

All the projections show that the cost of care of anaging population with the current rate of dementia is notsustainable. There is no country, neither the U.S., norJapan, nor Canada that is rich enough to afford care forelderly patients if the rate of dementia does not [change].

—Who’s making a difference near you? Tell The Chronicle, so we can tell our readers.

Write us at [email protected]

“The truth is that our finest moments are most likelyto occur when we are feeling deeply uncomfortable, unhappy,or unfulfilled. For it is only in such moments, propelled by ourdiscomfort, that we are likely to step out of our ruts and start

searching for different ways or truer answers.” —Dr. M. Scott Peck, American psychiatrist (1936-2005).

Dr. Benoit MulsantLeading Alzheimer’s disease prevention research

André Chagnon of the Chagnon Foundation (left), Dr. Naomi Azrieli, the Centre of Addiction and Mental health’s (CAMh) Dr. Benoit Mulsant, Canada’s Prime Minister Stephen harper, and the Universityof Mcgill’s Dr. Nahun Sonenberg, prior to the announcement by Brain Canada of $10 million to CAMh for Alzheimer’s prevention research.

Owen E

gan


For the second year in a row, Dr. Eve Tsai, assistant profes-sor at the Faculty of Medicine at the University ofOttawa, was named to the list of Canada’s Top 25

Women of Influence for 2012. Women of Influence maga-zine selected her in the health category to recognize her ground-breaking work in spinal cord surgery and her dedication in bring-ing researchers and clinicians together—turning research advancesinto therapies that can improve health care for patients. THECHRONICLE’S senior associate editor Lynn Bradshaw spokewith Dr. Tsai about her achievements.

How did you feel about starting medical school at 19 years of age?I did not think it was that big of a deal because atthat point in time students could get into medicalschool sometimes after completing two years ofundergraduate education.

Actually, I recall being interviewed as part of myentrance requirement to get into medical school andone of the individuals who interviewed me said,“Aren’t you a little young to be getting into medicalschool?” I said “If you are going by chronological agethen I cannot lie about my age. However, if you aregoing by ‘age’ based on maturity and by assessingachievements and interpersonal skills, then I thinkthere are many people who in chronological age areolder, but less mature. I think you have to go based onthe individual and not necessarily something such aschronological age.”

So at the age of 19, I did not feel I was too youngto be getting into medical school.

What made you decide to become a researcher,study medicine and become a neurosurgeon?My involvement in research began with participating in ascholarship program when I was in high school. The aimof the program that I was involved in was to encouragemale and female students to spend time working andlearning about non-traditional gender scientific and med-

ical professional fields. For example, in my case therewere not a lot of females working in research chemistry,therefore, I was assigned to work with a chemistry pro-fessor and during my time working with him, he intro-duced me to research. So that is what first got me inter-ested in research, science, and medicine.

The possibility of helping patients with spinal cordinjuries actually piqued my interest in becoming a neuro-surgeon. It seemed incredibly tragic that a person whowas in the prime of his/her life could be permanentlydisabled because of an accident or brief mistake in judg-ment. To be able to help these people is why I was inter-ested in neurosurgery and research in neurosurgery. Idecided that I wanted to commit my life to trying to treatand cure spinal cord injury.

What clinical research excites you the most and why?Translational research excites me, which involves actu-ally trying to bring some of the research advances for-ward to treat patients. So, in Ottawa for example, ourtranslational research consists of using new imagingtechniques to look at spinal cord tracts in patients. Incontrast in past years the best imaging tool we hadavailable was the use of MRI, but unfortunately, thatcame with limitations. While MRI was useful in that itallowed us to visualize the anatomy of neurologicalstructures better than ever before, routine MRI waslimited because it would not allow us to see the dam-aged fiber tracts, which made it difficult for us tounderstand how the fiber tracts are affected by tumoursand spinal cord injury.

With the use of new technology we have been ableto look at these fibers and improve our ability to oper-ate on these patients who have spinal cord tumoursand other kinds of lesions without damaging theirspinal cord.

Another aspect that we are really excited about isusing biomaterials to deliver the special factors,

growth factors and special substances that we need tohelp improve regeneration in the spinal cord. For thepurpose of developing these biomaterials we havebeen working with researchers from Ottawa, as well aswith investigators from, Germany, the United States,and Australia.

Overall, our research goal is to try to develop andadvance the use of biomaterials to hopefully help usregenerate and repair the injured spinal cord.

What was your reaction to being voted as one of thetop women of influence in Canada?I was and I am still pleased and thrilled to have beenvoted as one of Canada’s Top Women of Influence fortwo years in a row. But really winning this amazingrecognition in 2011 and in 2012 was not because of myefforts alone. Honestly, I could not have done it with-out my team members at the Division of Neurosurgeryat the Ottawa Hospital and the Ottawa HospitalResearch Institute and The University of Ottawa whoare remarkable.

How do you balance work, research, and personal time?In my opinion balancing work, research, and personaltime is not a problem if you are happy and like whatyou are doing. If you do not like what you are doingthen you may always be resentful of one thing or theother and that makes it become difficult to have anappropriate balance.

Personally, I am truly lucky that I actually like whatI am doing and I like both the research part of my joband the clinical delivery part that I partake in. I am for-tunate to have an amazing team not only at work, butat home. I am so grateful to have a partner and familywho are incredibly understanding and supportive.

—Who’s making a difference near you? Tell The Chronicle, so we can tell our readers.

Write us at [email protected]

“Life can be pulled by goals just as surely as it can bepushed by drives.”

—Dr. Viktor Frankl, Austrian neurologist and psychiatrist (1905-1997).

Alex VakulentoIntroducing the greenChronicle

Coming soon: A bimonthly electronic supplement to The Chronicle with original multimedia content inevery issue. Optimized for iPad, and readable on your computer, e-reader and electronic device.Interactive, real-time news, opinion and education in the CNS sciences, with two intriguing value-addedfeatures: It’s free. And no trees were harmed in the preparation of this journal.

Sign up for your free subscription now at www.chronicle.ca, and be among the first to receive the revolu-tionary greenChronicle. And while you’re at it, why not follow us on Twitter and Facebook?

Your device. Our content.(This could be the ultimate word-association.)

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April 2014_N_P.qxp_April 2014_N+P_ei_ar.qxd 2014-04-21 6:27 AM Page 19

Nicole*, 37

overwhelmed“I felt down and

nearly every day.”

No statistical diff erence in mean weight change vs. placebo was seen at 6 months (p=ns)†

Reference: PRISTIQ Product Monograph, Pfi zer Canada Inc., July 3, 2013.

PRISTIQ ® Wyeth LLC, owner/ Pfi zer Canada Inc., Licensee© 2013 Pfi zer Canada Inc.Kirkland, Quebec H9J 2M5

CA0113PRI023E

In major depressive disorder

* Fictitious case. May not represent all patients.† Results of the fi nal on-therapy assessment in the 6-month, double-blind, placebo-controlled phase of a long-term trial in patients who had responded to PRISTIQ during an initial 12-week, open-label phase.

Count on

for powerful symptom relief

Indication and clinical use• PRISTIQ is indicated for the symptomatic relief of major depressive disorder• PRISTIQ is not indicated for use in children under the age of 18• The short-term effi cacy of PRISTIQ has been demonstrated in placebo-controlled trials of up to 8 weeks

• The effi cacy of PRISTIQ in maintaining an antidepressant response for up to 26 weeks, following response during 20 weeks of acute, open-label treatment, was demonstrated in a placebo-controlled trial

Contraindications• Concomitant use with monoamine oxidase inhibitors (MAOIs) or within

the preceding 14 days• Hypersensitivity to venlafaxine hydrochloride

Most serious warnings and precautions

• Behavioural and emotional changes, including self-harm: SSRIsand other newer antidepressants may be associated with: - Behavioural and emotional changes including an increased risk

of suicidal ideation and behaviour - Severe agitation-type adverse events coupled with self-harm

or harm to others - Suicidal ideation and behaviour; rigorous monitoring advised

• Discontinuation symptoms: should not be discontinued abruptly. Gradual dose reduction is recommended

Other relevant warnings and precautions• Concomitant use with venlafaxine not recommended • Allergic reactions such as rash, hives or a related allergic phenomenon • Bone fracture risk with SSRI/SNRI • Increases in blood pressure and heart rate (measurement prior to

and regularly during treatment)

• Increases cholesterol and triglycerides (consider measurement during treatment) • Hyponatremia or Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

with SSRI/SNRI • Potential for GI obstruction • Abnormal bleeding with SSRI/SNRI • Interstitial lung disease and eosinophilic pneumonia with venlafaxine • Seizures • Narrow angle glaucoma • Mania/hypomania • Serotonin syndrome or neuroleptic malignant syndrome-like reactions

For more informationPlease consult the product monograph at http://www.pfi zer.ca/en/our_products/products/monograph/226 for important information relating to adverse reactions, drug interactions and dosing information which have not been discussed in this piece.

The product monograph is also available by calling 1-800-463-6001.

for powerfulsymptom relief

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