医薬品相互作用研究

Vol.39, No. 2（2015）

9（73）

医薬品相互作用研究
一
般論
文
39（2） 9-17 （2015）

Prescription of drugs for children with attention-deﬁcit/hyperactivity
disorder (ADHD) in Japan: a study based on health insurance claims data
Taku Obara1,2,3）, Michihiro Satoh3）, Nobuhiro Ooba4,5）, Yoshihiko Morikawa6）,
Hidekazu Nishigori7）, Nariyasu Mano3）
1）

Division of Preventive Medicine and Epidemiology, Tohoku University Tohoku Medical Megabank Organization
2）
Division of Molecular Epidemiology, Tohoku University Graduate School of Medicine
3）
Department of Pharmaceutical Sciences, Tohoku University Hospital
4）
Department of Pharmacoepidemiology, Graduate School of Medicine, University of Tokyo
5）
Department of Clinical Pharmacy, Nihon University School of Pharmacy
6）
Clinical Research Support Center, Tokyo Metropolitan Children's Medical Center
7）
Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine（Received July 28, 2015; Accepted September 11, 2015）

In Japan, methylphenidate osmotic controlled release oral delivery system (OROS) tablets and atomoxetine
were approved for children with attention deficit hyperactivity disorder (ADHD) in 2007 and 2009, respectively.
However, the annual change of medications for ADHD children has not been evaluated in Japan. Only two drugs
are now available for children with ADHD in Japan. It was previously reported that many medications prescribedto children were classed as off-label utilization in Japan. The aim of the present study was to provide
information on the use of drugs prescribed to children with ADHD in Japan before and after the approval of
methylphenidate OROS tablets and atomoxetine. A retrospective study was conducted with Japanese medical
claims data from January 2005 to December 2010 to examine the use of drugs in children with ADHD in Japan.
The prescription rate of methylphenidate tablet/powder decreased from 13.4% in 2005 to 0.5% in 2008 (trend
P<0.0001). This fall was accompanied by a rapid rise in the prescription rate of methylphenidate OROS tabletsfrom 19.5% in 2008 to 31.2% in 2010 (trend P<0.0001). The prescription rate of atomoxetine also increased,reaching 3.8% in 2009 and 13.0% in 2010 (trend P<0.0001). The prescription rate for risperidone, aripiprazole,
valproate, and fluvoxamine increased (all trend P<0.05), but none of the other drugs showed any change in the
profile of annual changes in prescription rates. It was found that prescription patterns of drugs for children with
ADHD changed before and after the approval of methylphenidate OROS tablets and atomoxetine in Japan. We
need to establish the drug safety monitoring system for children with ADHD.
Key Words: : attention deficit hyperactivity disorder, children, methylphenidate, atomoxetine

Backgroundtreatment options for pediatric ADHD patients are

Methylphenidate osmotic controlled release oral

limited, with only methylphenidate OROS tablets

delivery system (OROS) tablets and atomoxetine

and atomoxetine indicated for ADHD in children.

were approved for children with attention deﬁcit

In contrast, the US has approved a range ofhyperactivity disorder (ADHD) in 2007 and 2009,

central nervous stimulants such as amphetamines

respectively, in Japan. However, pharmaceutical(which are not sold in Japan), and it is possible

Division of Preventive Medicine and Epidemiology, Tohoku University Tohoku Medical Megabank Organization, 2-1 Seiryo-cho,Aoba-ku, Sendai, Miyagi 980-8573, Japan
2）
Division of Molecular Epidemiology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi
980-8573, Japan3）
Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8574, Japan
4）
Department of Pharmacoepidemiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
5）
Department of Clinical Pharmacy, Nihon University School of Pharmacy, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan
6）
Clinical Research Support Center, Tokyo Metropolitan Children's Medical Center, 2-8-29, Musashicai, Fuchu, Tokyo 183-8561, Japan
7）
Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi
980-8574, Japan
連絡著者： Taku Obara (E-mail: obara-t@hosp.tohoku.ac.jp)1）

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医薬品相互作用研究

Vol.39, No. 2（2015）that some of these medications available overseas

fall into the categories of behavioral disorders,have been used oﬀ-label for pediatric ADHD

emotional disorders, nervous habits, andpatients in Japan. In fact, a report by a researchdevelopmental disorders. Under the ICD-10

group of the Ministry of Welfare over 10 years

classiﬁcation, ʻbehavioral disordersʼ corresponds toago stated that 76.6% of medications prescribed

conduct disorders (F91) including oppositional

to children were classed as oﬀ-label ut ilizat ion

deﬁant disorder (F91.3) and unsocialized conduct(http://mhlw-grants.niph.go.jp/

disorder (F91.1); ʻemotional disordersʼ corresponds

niph/search/NIDD00.do?resrchNum=199900758

to phobic anxiety disorders (F40), other anxiety

A). Also, in foreign countries, oﬀ-label drugs are

disorders (F41), adjustment disorders (F43.2),

1）often used for children with ADHD . However, them o o dd i s o r d e r s( F 3 0 - 3 9 ) ,a n dannual change of usage of medications for ADHD

obsessive-compulsive disorder (F42); ʻnervous

children before and after the approval of

habitsʼ corresponds to nonorganic enuresis

methylphenidate OROS tablets and atomoxetine(F98.0), nonorganic encopresis (F98.1), tic

for children with ADHD has not been evaluated indisorders (F95), nonorganic sleep disorders (F51),

Japan. The aim of the present study was to clarify

sleep disorders (G47), and stuttering [stammering]

the annual change of usage of medications among(F98.5); and ʻdevelopmental disordersʼ corresponds

children with ADHD in Japan before and after theto speciﬁc developmental disorders of scholastic

approval of methylphenidate OROS tablets andskills (F81), speciﬁc developmental disorder of

atomoxetine.

motor function (F82), and pervasive developmental
disorders (F84), and patients not falling under any

Methods
1. Subjectsof the above were deﬁned as having ʻnodevelopmental disordersʼ.

Health insurance claims data held by the Japan
Medical Data Center ( JMDC) 2 ) were used. Of the

3. Data collection method

3,667,503 National Health Insurance beneﬁciaries

Hospital admission/non-admission claims data

between January 1, 2005 and June 30, 2011, thesubmitted when a patient attended a hospital or

JMDC held in its database the claims data forclinic, and pharmacistsʼ fee claims data submitted

2,844,948 people (77.6%) for whom claims had

when a drug was dispensed by a pharmacy based

been issued. In conducting this study, the claims

on a prescription were used. The name of thedata of patients aged 2 to 17 years with andisorder, ICD-10 code, and date of diagnosis wereInternational Classiﬁcation of Diseases (ICD)-10

extracted from the hospital admission/

diagnosis of F80-F89 (disorders of psychologicalnon-admission claims data. The brand name,development) and/or F90-F98 (behavioral andgeneric name, and dosage of the prescribedemotional disorders with onset usually occurring

medication were extracted from the hospitalin childhood and adolescence), were received fromadmission/non-admission claims data anda total of 823,354 patients aged under 20 years

pharmacistsʼ fee claims data. The year, month, andfor whom a health insurance claim had been

day of prescription could be extracted from theprocessed. The target of the analysis was pediatricpharmacistsʼ fee claims data, but since the exact

pat ients new ly diagnosed w ith ADHD (F90.0 inprescription date does not appear in hospital

ICD-10) within the period from January 1, 2005 toadmission/non-admission claims data, theDecember 31, 2010. Patients reaching 18 years ofprescription date was deﬁned as the ﬁrst day of theage during the target analysis period weremonth of medical examination. Where there was

excluded from the prescription data for that year

overlap of pharmacistsʼ fee claims data andand subsequent years.

hospital admission/non-admission claims data, thep h a r m a c i s t sʼ f e e c l a i m s d a t a t o o k p r e c e d e n c e

2. Comorbidities

because of the greater precision of the prescription

According to the Japanese guidelines on thedate. The World Health Organization - Anatomical

diagnosis and treatment of ADHD 3) , comorbidities

Therapeutic Chemical (WHO-ATC) codes using the医薬品相互作用研究

Vol.39, No. 2（2015）

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ATC classiﬁcation system, ﬁrst published in 1976

prescription rates for these two forms wereby the WHO Collaborating Centre for Drugtabulated separately. Prescription rates for eachS t a t i s t i c s M e t h o d o l o g y, w e r e a s s i g n e d t o e a c hcomorbidity in 2010 were calculated to ascertain

medication 4).

annual changes in all extracted ATC class names
and the generic names of the 30 most frequently

4. Extraction and tabulation of drug data

prescribed drugs in 2010, and to investigate

The claims data used in this research contained

diﬀerences according to comorbidity.

339 drug types as classiﬁed by ATC class nameand 2,585 drug types by generic name. For this

5. Statistical analysis

research, drugs excluding ʻother general

To analyze the relationship between years andanestheticsʼ, ʻinhalational anestheticsʼ, ʻother local

age or sex, we compared means and proportions

anestheticsʼ, ʻtopical local anestheticsʼ, ʻinjectedusing analysis of variance (ANOVA) and the

local anestheticsʼ, ʻnon-narcotic and antipyreticchui-square test for univariate analysis. We

analgesicsʼ, ʻdrugs used in opioid dependenceʼ, andexamined trends in prescription medications usingʻnarcotic analgesicsʼ were extracted from the classmultiple logistic analyses with adjustments for sexof nervous system drugs, as identiﬁed by the initialand age. The values are expressed as means +/-W H O - AT C c o d e ʻ N ʼ . P r e s c r i b e d d r u g s w e r estandard deviation unless otherwise noted. All datatabulated for each year from 2005 to 2010 towere statistically analyzed using SAS version 9.3

exclude the eﬀect of variations in prescription oversoftware (SAS Institute, Cary, NC, USA). The level ofthe course of a year. A drug was deemed to havesigniﬁcance was P<0.05.

been prescribed in a given year even if only
prescribed once in that year. In order to calculate

Resultsprescription rates, the number of patients

The prevalence of pediatric ADHD patientsprescribed a particular drug was taken as theslightly increased (Table 1), with boys accounting

numerator, and the cumulative number of ADHD

for over 85% in each year. In each ATC class name,patients under 18 years of age up to the end of

there was a consistent increase from 2005 to 2010

each prescription year was taken as thein prescript ions of psychost imulants, all otherdenominator. Tabulation was done for each ATCagents aﬀecting the central nervous system, andclass name and generic name, and as a rule, dosage

atypical antipsychotics (trend P<0.0001).

form was ignored. However, because of diﬀerences

Psychostimulants had the highest prescription ratein the approval condit ions of methylphenidateof all these drug classes in 2010. Other ATC class

OROS tablets and other dosage forms, andnames other than select ive serotonin reuptake

diﬀerences of the prescription rates between

inhibitors (SSRIs) showed no consistent annual

diazepam suppositories and other dosage forms,

changes in prescription rates (Table 2).

Table 1. Characteristics of patients with ADHD by year
Year of diagnosis

2005

2006

2007

2008

2009

2010

Number of all patients
aged 0–20 years in
the database

42,07145,12547,442

112,695

163,496258,431

Cumulative number of
ADHD patients, n (%of the all patients
aged 0-20 years in
the database)67 (0.16)

144 (0.32)

245 (0.52)

430 (0.38)

665 (0.41)

1,021 (0.40)<0.0001

Age, years

8.3±3.2

8.7±3.1

9.5±3.1

9.9±3.2

10.1±3.2

10.6±3.3<0.0001

Boys, n (%)

66 (98.5%)

125 (86.8%)215 (87.8%)

380 (88.4%)

577 (86.8%)

874 (85.6%)

0.06

Data are expressed as mean ± standard deviation or percentage. ADHD, attention deﬁcit hyperactivity disorder.

P12（76）

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Vol.39, No. 2（2015）

Figure 1 shows annual changes in prescription

developmental disorders in 406 patients, anxiety

rates for methylphenidate tablet/powder,and other emot ional disorders in 123 pat ients,

methylphenidate OROS tablets, and atomoxetine.

epilepsy in 112 patients, tic disorders and other

The prescription rate of methylphenidaten e r vo u s h a b i t s i n 8 8 p a t i e n t s , a n d b e h a v i o r a ltablet/powder decreased from 13.4% in 2005 todisorders in 12 patients. Prescription rates for

0.5% in 2008 (trend P<0.0001). This fall waspatients with emotional disorders and epilepsy

accompanied by a rapid rise in the prescription

were relatively higher than for other comorbidities.

rate of methylphenidate OROS tablets from 19.5%

For emotional disorders, the rates were 52.0% forin 2008 to 31.2% in 2010 (trend P<0.0001). The

methylphenidate OROS tablets, 12.2% forprescription rate of atomoxetine also increased,

ﬂuvoxamine, and 10.6% for aripiprazole, and forreaching 3.8% in 2009 and 13.0% in 2010 (trend

epilepsy, the rates were 37.5% for valproic acid,P<0.0001). The prescription rate for risperidone,

19.6% for carbamazepine, and 17.0% for triclofos.

aripiprazole, valproate, and ﬂuvoxamine increased

In patients with no developmental disorders, not(all trend P<0.05), but none of the other drugs

only methylphenidate OROS tablets (18.7%) andshowed any change in the proﬁle of annual

atomoxetine (6.8%) but also risperidone (2.3%),

changes in prescription rates (Figure 2, Table 3).

valproate (0.4%), triclofos (1.9%), and aripiprazole

Table 4 shows drug prescription rates for each

(1.0%) were prescribed.

comorbidity in 2010. Prescriptions were given for

Table 2. Annual changes of drug prescriptions among children with ADHD

Prescription year

2005

2006

2007

2008

2009

2010

Cumulative number of ADHD patients, n

67

144

245

430

665

1021

Psychostimulants

13.4

11.1

9.0

20.0

22.7

31.5

<0.0001

All other central nervous system drugs

0.0

0.7

0.0

0.0

4.4

13.5

<0.0001

Atypical antipsychotics

1.5

0.0

0.8

5.6

6.6

11.6

<0.0001

Other antipsychotics

1.5

2.1

0.8

0.7

0.5

2.0

0.7

Sex- and ageadjusted trend P

Prescription rate, %Psychostimulants, etc.

Antipsychotics

Antidepressants
SSRI antidepressants

0.0

0.0

0.4

1.2

1.1

2.5

0.007

SNRI antidepressants

0.0

0.0

0.0

0.0

0.0

0.2

NA

Other antidepressants

3.0

2.1

1.6

1.6

1.4

1.9

0.3

Antianxiety drugs (tranquilizers)

3.0

3.5

1.2

2.1

2.0

3.0

0.7

Mood stabilizers (antimanic drugs)

0.0

0.0

0.0

0.2

0.2

0.1

1.0

Psychotropic drugs (either of above)

17.9

15.3

12.2

24.2

29.0

45.5

<0.0001

Antianxiety / mood stabilizer drugs

OthersAntiepileptic drugs

6.0

5.6

5.3

5.8

6.0

8.5

0.1

Barbiturates, single drug

1.5

1.4

0.4

0.5

0.9

0.6

0.6
0.3

Non-barbiturates, single drug

4.5

6.3

2.9

3.3

3.8

4.9

Parkinson's disease / syndrome drugs

0.0

0.7

0.0

0.7

0.9

1.2

0.2

Triptans for migraine

0.0

0.0

0.0

0.0

0.0

0.1

NA

Other drugs for migraine

0.0

0.0

0.0

0.0

0.0

0.1

NA

Anti-vertigo drugs

0.0

0.0

0.0

0.0

0.2

0.0

0.9

Nootropic drugs (cognitive enhancers)

0.0

0.0

0.0

0.0

0.0

0.1

NA

Prescription rates for each generic name were calculated as percentage values using the number of patients prescribed eachdrug as the numerator and the cumulative number of ADHD patients age <18 years up to each prescription year as thedenominator. ADHD, attention deﬁcit hyperactivity disorder; SNRI, serotonin and norepinephrine reuptake inhibitor selective;
SSRI, selective serotonin reuptake inhibitor. NA, not applicable (because of the limited number of drug prescription)

医薬品相互作用研究

Vol.39, No. 2（2015）

Figure 1. Annual changes of prescription rates of methylphenidate tablet/powder,
methylphenidate OROS tablets, and atomoxetine for children with ADHD in Japan
Prescription rates of methylphenidate tablet/powder, methylphenidate OROS tablets, and atomoxetine were
calculated as percentage values using the number of patients prescribed each drug as the numerator and thecumulative number of ADHD patients age <18 years up to each prescription year as the denominator. ADHD,
attention deﬁcit hyperactivity disorder; OROS, osmotic controlled release oral delivery system. All trend P
values were <0.0001 after adjustment for sex and age.

Figure 2. Drugs whose prescription rates were in the top 3-10 for year 2010 and their annualchanges
Prescription rates for each generic name were calculated as percentage values using the number of patientsprescribed each drug as the numerator and the cumulative number of ADHD patients age <18 years up to eachprescription year as the denominator. Because diﬀerences were seen in prescription rates for diazepam
suppository and its other dosage forms, the prescription rates were calculated separately for the suppository.
ADHD, attention deﬁcit hyperactivity disorder. Trend P values were <0.0001 for risperdone, 0.002 foraripiprazole, 0.01 for valproate, 0.9 for carbamazepine, 0.7 for triclofos, 0.02 for ﬂuvoxamine, 0.9 for diazepam
suppository, and 0.7 for chloral hydrate after adjustment for sex and age.

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Table 3. Drugs whose prescription rates were in the top 11-30 for year 2010 and their annual changes

Year of diagnosis

2005

2006

2007

2008

2009

2010

Cumulative number of ADHD patients, n

67

144

245

430

665

1021

Sex- and ageadjusted trend P

Prescription rate, %Hydroxyzine

1.5

2.8

0.8

0.9

1.2

1.3

0.7

Clomipramine

0.0

0.7

1.2

1.2

0.9

1.0

0.7

Imipramine

3.0

1.4

0.4

0.5

0.3

0.8

0.1

Diazepam other than suppository

0.0

0.7

0.0

0.0

0.3

0.8

0.1

Sertraline

0.0

0.0

0.0

0.5

0.5

0.8

0.2

Propericiazine

1.5

0.7

0.4

0.2

0.3

0.7

0.8

Biperiden

0.0

0.7

0.0

0.2

0.3

0.7

0.4

Clobazam

1.5

0.7

0.8

0.7

0.8

0.6

0.2

Haloperidol

0.0

0.7

0.0

0.2

0.2

0.5

0.6

Phenobarbital

0.0

0.7

0.0

0.2

0.6

0.5

0.3

Clonazepam

0.0

0.7

0.8

0.7

0.5

0.4

0.5

Brotizolam

0.0

0.0

0.0

0.0

0.6

0.4

0.2

Lamotrigine

0.0

0.0

0.0

0.0

0.3

0.4

0.1

Levomepromazine

1.5

0.7

0.0

0.0

0.0

0.3

0.2

Pimozide

0.0

0.7

0.4

0.2

0.0

0.3

0.6
0.7

Neostigmine

0.0

0.7

0.0

0.0

0.5

0.3

Ethyl loflazepate

0.0

0.0

0.4

0.0

0.0

0.3

0.6

Olanzapine

0.0

0.0

0.0

0.0

0.2

0.3

0.3

Levodopa

0.0

0.0

0.0

0.0

0.2

0.3

0.3

Prescription rates for each generic name were calculated as percentage values using the number of patients prescribed eachdrug as the numerator and the cumulative number of ADHD patients age <18 years up to each prescription year as thedenominator. ADHD, attention deﬁcit hyperactivity disorder.

Table 4. Prescription rates of major drugs by comorbidities in 2010

Developmental
disordersEmotional
disorders

Nervous habits

Epilepsy

No develop-mental disorder

406

123

88

112

486

Methylphenidate
OROS tablets

41.1

52.0

36.4

39.3

18.7

Atomoxetine

17.2

24.4

25.0

21.4

6.8

Risperidone

17.5

26.8

19.3

25.9

2.3

Valproate

7.1

11.4

11.4

37.5

0.4

Triclofos

3.2

0.8

3.4

17.0

1.9

Carbamazepine

3.9

5.7

9.1

19.6

0.0

Aripiprazole

4.2

10.6

6.8

5.4

1.0

Fluvoxamine

2.7

12.2

4.5

1.8

0.0

Number of patients, n
Prescription rate, %Prescription rates for each generic name of major drugs by comobidities were calculated as percentage values using the numberof patients prescribed each drug as the numerator and the number of ADHD patients age <18 years for year 2010 as thedenominator. Because behavioral disorders were observed only in 12 children, the results were not shown. OROS, osmotic
controlled release oral delivery system. ADHD, attention deﬁcit hyperactivity disorder.

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Discussion

recommended as ﬁrst- or second-line treatment in

The present study found that methylphenidate

all guidelines. It is unclear from the present study

tablet/powder might have been mainly used forwhether the prescribed medications were used as

children with ADHD before the approval ofﬁrst-line therapy. However, a questionnaire survey

methylphenidate OROS tablets and atomoxetine,of Japanese physicians on prescribing practices forand the prescript ion rates of methylphenidate

drug treatment of pediatric ADHD patients found

OROS tablets and atomoxetine increased in recent

that methylphenidate OROS tablets andyears. Many medications not indicated for ADHD in

atomoxetine were prescribed as ﬁrst- andchildren have also been used in these pat ients,

second-line drugs by 92.5% and 89.4% ofsuggesting the possibility that these medications

respondents, respectively 9).
Apart from methylphenidate OROS tablets andhave been used oﬀ-label to treat ADHD.
According to several reports on drug utilization

atomoxet ine, pediatric ADHD pat ients in Japanin children (0 to 17 years) in the US, methylphenidate

have often been prescribed antipsychotics,

and amphetamine salts are widely used as ADHD

antidepressants, antiepileptic drugs, andmedications, whereas atomoxetine, which is on thenonbarbiturate agents. It is possible that

increase in Japan, is seeing a downward trend inprescribing trends among physicians diﬀer

the US, while utilization of dexmethylphenidate,according to type of comorbidity and guidelines

5)

lisdexamfetamine, and guanfacine has increased .

consulted, and this may be a factor in the oﬀ-label

There is also a slight upward trend in theuse of drugs to treat pediatric ADHD in Japan. The

utilization of central nervous system agents, which

present study suggested that risperidone,

5,6). Thesevalproate, triclofos, and aripiprazole might bestudies illustrate the diﬀerence in utilization ofprescribed as oﬀ-label use in pediatric ADHD

ADHD medications between Japan and other

patients. In the questionnaire survey of Japanesecountries, and this highlights the need for aphysicians mentioned above, many respondents

Japan-speciﬁc understanding of drug utilization.

cited risperidone, aripiprazole, antiepileptic drugs,

include ADHD medicat ions, in the US

Diﬀerences in utilization of ADHD medications

and SSRIs as drugs they would like to see approved

are presumably greatly inﬂuenced by the content

for clinical use in children w ith developmentalof diﬀerent ADHD treatment guidelines,

disorders 9) . It is therefore likely that some drugs

irrespective of diﬀerences in indications andare knowingly used oﬀ-label because physicians

oﬀ-label use. The guidelines for the diagnosis andare forced by necessity to do so. Given thetreatment of ADHD in Japan recommend

possibility that patients suﬀering adverse reactions

methylphenidate OROS tablets and atomoxetine asfollowing oﬀ-label use might not receive the3)

ﬁrst-line drugs . In the US, the Texas Children's

appropriate remedial care, there is an urgent need

Medication Algorithm Project recommends central

to gather data to evaluate eﬃcacy and safety based

nervous stimulants, such as methylphenidate, as

on actual utilization, to decide whether or not toﬁrst-line drugs, and combined use of atomoxetine

expand the indications, and to eliminate

and central nervous stimulants, as well as

discrepancies between package inserts andantidepressants (serotonin and norepinephrine

guidelines, using health insurance claims data andreuptake inhibitors; SNRIs) and alpha-2 agonists,

other information sources.

7)

as second-line drugs and beyond . European

R e c e n t l y, c a s e s o f s u d d e n d e a t h , m y o c a r d i a lclinical guidelines for hyperkinetic disorderinfarction, and stroke among children who wererecommend central nervous stimulants, such astreated w ith drugs for ADHD were reported as

methylphenidate, as ﬁrst-line drugs, andadverse events in Canada and the United States 10,11).

noradrenergic agents, such as atomoxetine, if there

In response, the United States Food and Drug8)

is no improvement . One of the reasons for the

Administration (FDA) and the Agency forwide use of methylphenidate and atomoxetine seen

Healthcare Research and Quality (AHRQ) embarked

in this study might be that, in addition to being

on a large-scale, joint study of ADHD medications

approved for ADHD in Japan, these drugs are

and cardiovascular risk using health insurance

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Vol.39, No. 2（2015）

data 12). The study concluded that even if there is an

Japan (H24-iyaku-wakate-011). The authors would

increased risk, the absolute risk is low, and there is

like to thank the Research Group for Healthno evidence of a link between current use of ADHD

Administrative Data and the Japan Medical Data

medicat ion and serious cardiovascular risk12).

Center Co., Ltd.

Subsequently, however, eﬀects of ADHD

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