Volume 13, Number 3 | Fall 2018

Type 3 Case of Yasui Classification
Effects of Kampo Medicines on Loss of Appetite
and Irritation Caused by Attention Deficit
Hyperactivity Disorder Medicationchemotherapy3)4). In this study, we examined theeffects of Kampo medicines administered to treat
loss

Kaori Kimataofappetite

andirritability

due

totheadministration of MPH and ATX.

Kawashima Family Clinic

Patients and Methods
Patients included 20 pediatric males who visited

Abstractsustained-our developmental outpatient clinic during the 4

release tablets and atomoxetine hydrochloride areyears between January 2014 and May 2017 and werepreferred drug treatments for attention deficit

prescribed MPH or ATX. They exhibited loss of

hyperactivity disorder (ADHD), but both drugs often

appetite and irritability, for which Kampo drugs

cause loss of appetite or irritability. In this study, wewere additionally prescribed. The patients were all

examined the effects of shikunshito and rikkunshito

males and between 6 and 14 years of age at the timeadministered to alleviate these adverse effects.

of Kampo medicines administration. Six patients

Althoughhad comorbid autistic spectrum disorder.

Methylphenidate

therehydrochloride

werecases

inwhichoral

administration was not possible due to the taste or

ADHD medication doses were ATX 50 mg/day (nof= 1), MPH 18 mg/day (n = 8), MPH 18 mg/day (n = 1),appetite improved in 1–2 months. Because patients

ATX 10 mg/day (n = 1), and MPH 27 mg/day (n = 10)with ADHD are often “inattentive,” missed doses did(Table 1). Loss of appetite, as a consequence of MPH

occur; however, it was considered that patientsadministration, tended to increase in severity with

continued taking Kampo because they felt it was

the dose. It often appeared from the day theeffective. Many children with ADHD experience

medication was administered. We attempted tostress related to their condition and may have low

prevent a significant decrease in daily intake byself-esteem. Considering such condition of children

reducing the amount of school lunch that thewith ADHD as “qi-kyo (qi deficiency),” shikunshito

children consumed for the first 1–2 weeks afterand rikkunshito improved gastrointestinal motility

starting the medication, while increasing theand sustained patient motivation.

number of snacks and amount of food served atformulation,

following

administration,

lossdinner. If loss of appetite persisted for ≥1 month or
Keywords: attention deficit hyperactivity disorder,worsened due to environmental changes, Kampo

loss of appetite, shikunshito, rikkunshito

medicines were added.

Rikkunshito extract granules (Tsumura & Co.,Tokyo, Japan) at 5.0 g/day or shikunshito extract

Introduction
Drug treatment for attention deficit hyperactivity

tablets (Osugi & Co., Osaka, Japan) at 12 tablets/day

methylphenidate

were administered before breakfast and dinner totablets(MPH),

combat loss of appetite. We explained the taste andcovered by health insurance for children since 2007,

formulations of the drugs to the patients and theirand atomoxetine hydrochloride (ATX), covered sinceparents or guardians. In cases where the patient2009. As both drugs sometimes cause loss of appetite

could only tolerate the granulated formulation,

disorder(ADHD)

hydrochlorideincludes

sustained-release

discontinued prior to achieving their optimal effects.

rikkunshito extract granules were prescribed. If thepatient preferred tablets, we prescribed shikunshito

Reports indicate that rikkunshito is an effective

extract tablets.

as a side effect1)2), these medications are often

treatment for loss of appetite in patients undergoing

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

9Volume 13, Number 3 | Fall 2018

In terms of response evaluation, we considered

Three cases exhibited irritability and frequent

the drugs to be effective if consumption of foodepisodes of crying in addition to loss of appetite;

increased by more than half at school lunch. The

therefore, we added 2.5 g/day of kanbakutaisouto

medications were considered ineffective if loss of(Tsumura & Co., Tokyo, Japan) before dinner. In 3

appetite persisted, or if the dose of MPH or ATX hadcases with continuous irritability and agitation,

toconsidered unknown if oral administration could not

shikunshito was discontinued and switched todaisaikoto extract tablets (Osugi & Co., Osaka,

be continued or evaluation was difficult due to poorJapan)

medication compliance.

switching Kampo medicines, the patients withbereduced.

The

medication

effects

wereat 6 tablets/day before breakfast. After

irritability showed improvement in symptoms. The
Results

followingKampo

medicines

wereadditionallyThe results of this investigation are depicted inprescribed: hangekobokuto for severe anxiety (n = 1);

Table 1. Of the 20 patients, 2 took rikkunshito
extract granules, and 18 patients took shikunshito

shokenchuto for repeated abdominal pain (n = 2);
goreisan for nausea (n = 1); and hangeshashinto for

extract tablets. Many of the patients were sensitive

sustained diarrhea (n = 1). Due to the small sample

to the drug formulation, smell, or taste and therefore

size, individual examinations of each side effect wererefused the granular formulation or could not

not performed.

continue to take the granular formulation because oftime constraints. In those cases, shikunshito extract

Case presentationtablets, with similar crude products and indications

Case 10: A 10-year-old 5th grade male student.

as rikkunshito, were prescribed so that the patients

At first consultation: The patient was in 3rd grade.

could continue to take the medication.

He visited the clinic accompanied by his mother.

We found that patients often forgot to take theChief complaint: The patient was advised by hisdrugs before dinner. Twelve patients took theirclassroom teacher to consult a developmental

medication only once in the morning, and 8 patients

outpatient clinic for his poor conduct in the

took their medications twice per day, every morningclassroom.

and evening. Appetite stimulation effects were “good”

Patient’s complaints: difficulty in listening to others,in 16 cases, had “no effect” in 3 cases, and wereoften spilling drinks; often getting lost during early“unknown” in 1 case. Ten patients out of the 16 thatchildhood, restlessness at home, and frequent

exhibited a “good” response to the drug discontinued

movement.

the medication within 2 months. In 14 cases,Parental

administration of Kampo medicines was started

patient’s condition, the mother requested thatbetween July and November, indicating that more

pharmacologicalpatients appeared to experience loss of appetite

patient’s mother also wanted to better understandduring summer or at the start of sports day practice.

the patient’s psychological status.

There was no case in which drug therapy for

Perinatal period: Unremarkable.

concerns:

If

medicine

treatment

beimprovedinitiated.

theTheADHD was discontinued due to sustained loss ofDevelopmental history: During early infancy, theappetite. In 1 case, the dose was reduced due to loss

patient was sensitive to sound and was a shallow

of appetite and nausea, and in another case, the dosesleeper. He did not exhibit stranger anxiety.

was reduced because the patient’s ADHD symptoms

At 1 year of age, the patient started running as soon

improved.

as he started walking. Patient had delayed speech
and began speaking words at the age of 22 months.

10The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

Volume 13, Number 3 | Fall 2018

At 2 years of age, he had difficulty understanding,some extent. MPH (CONCERTA®) was started foreven when auditory information was repeatedly

hyperactivity and impulse control. The patientpresented. He liked to climb to high places and wasstarted taking MPH at 18 mg/day during therestless, with frequent movement. At 3 years of age,summer vacation prior to the 3rd grade, and loss ofhe frequently misbehaved, despite warnings, andappetite appeared on the first day of drug

was restless. He showed great interest in letters andadministration. Starting in September, we reduced

numbers. At 4 years of age, he showed no avoidance

the amount of food served during school lunch byof dangerous activities and required repeatedhalf and increased the amounts of snacks and dinner.

redirection. He talked about many things, but didWhen sports day practice started in early

not understand the feelings or positions of others. HeSeptember, he also experienced loss of appetite in thewas obsessed with winning and losing and had

evening and his daily intake decreased to about halftrouble maintaining friendships. Additionally, heof pre-medication levels. Because the patient wasoften forgot his belongings.

unable to take the granulated formation, we[ADHD checklist (behavioral questionnaire) forprescribed shikunshito extract tablets at 12 tablets

children aged ≥6 years]/day before breakfast and dinner. Although theInattention (7 points): does not pay attention topatient was actually taking shikunshito only before

details while studying; has difficulty focusing on

breakfast, his appetite improved about 1 week after

activities; cannot listen to instructions to the end;

starting the medication. At this time, the patient

avoids tasks; often gets distracted; has difficulty

was eating half of his school lunch and all of hislearning tasks and activities in order; does not seemdinner each day. After the sports day ended into hear when being spoken to.

October, he started to eat the full amount of school

Hyperactive/impulsive (5 points): restless andkeeps moving; cannot keep still; talkative; answers
questions without listening to the end; leaves seatlunch. After 1 month, his appetite improved, andshikunshito was discontinued.
After starting MPH at 18 mg/day, he could remain

when required to be seated.

calm in class for longer periods and required less

Treatment course:

frequent redirection by the classroom teacher.

We encouraged the family, especially the mother,and the classroom teacher to understand thedevelopmental

characteristics

discussed

following

hours.

ADHDandIn the 4th grade, he started to receive special

recommendations:(1)

guidance, in addition to his general classwork. At ouradjustment of the environment, such as reducing

clinic, we started to provide social skill training withwall hangings that may be distracting; (2) how to

the help of a psychotherapist and separately

talk to the patient, such as giving instructions

interviewed the patient and his mother. Whenseparately for each item, and sending a signal to pay

practice for the sports day started in September, theattention; and (3) how to support the patient when

patient found it difficult to focus and participate

he gets in trouble. We had an individual interview

during class. He continued to be absentminded andwith the patient once a month, where we observed

spent

the patient could not help touching whatever he saw,

disconnected from class activities. Then MPH dose

frequently turned around in his chair, switched fromwas increased to 27 mg/day. While the patient was

one topic to another during conversations, andunder observation, his appetite decreased, and heconstantly moved around during games, indicating

was barely able to eat school lunch. Beginning intheofHowever, while learning at home, he often cried fortime

playing

alone

with

hishands,

an inability to complete a conversation or a game to

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

11

Volume 13, Number 3 | Fall 2018

November, we prescribed shikunshito extract tablets

report describes the effects of rikkunshito for stress-at 6 tablets/day before breakfast.

related loss of appetite, focusing on serotonergic

After taking Kampo medicines, his appetite

neurons involved in eating behavior4).

calm and participated in class while at school, andShikunshito consists of Ginseng Radix,
Atractylodis Rhizoma, Poria, Glyzirrhizae Radix,
Zingiber Rhizoma, and Zizyphi Fructus. A
combination of Ginseng Radix, Atractylodis Rhizoma,Poria, and Glyzirrhizae Radix are the crude productsof ninjinto, to which Poria is added instead of Zizyphi

he was more easily able to complete his homework.

Fructus. Its diuretic effects are enhanced, and it is

At present, the patient has been taking MPH at 27

more effective for phlegm-dampness pattern than for

mg/day for 6 months along with shikunshito.

ninjinto. This formulation tonifies qi and is used toreturned to the same level as when he was taking 18
mg/day of MPH, and he was once again able to eat
half of his school lunch. After

increasing MPH doseto 27 mg, he was able to listen to instructions ingroup settings and throughout the day. He remained

treat impaired digestion and absorption (weaknessDiscussionof the stomach and spleen)5). The difference betweenhallmark symptoms of ADHD, by activating therikkunshinto and shikunshito is that shikunshito
contains neither Pinelliae Tuber, which suppresses

dopaminergic nervous system. MPH also suppresses

nausea and vomiting due to gastric fluid retention,eating behaviors, which can lead to a loss of

nor Citri unshiu Pericarpium, which removesappetite1)2). Loss of appetite is generally self-limiting

phlegm; thus, shikunshito has no effect on nausea.

and improves within 2–3 weeks, but if it does not
improve, this adverse effect can alleviate byRikkunshito extract granules at 5.0 g/day or
shikunshito extract tablets at 12 tablets/day before

withdrawing the drug during weekends or reducing

breakfast and dinner were prescribed for loss ofthe drug dosage. There have been reports on theappetite secondary to ADHD treatment drugs. In

effects of rikkunshito on loss of appetite duringcases in which oral administration was continued,

chemotherapy3),4), and we hypothesized that Kampo

the effects of rikkunshito and shikunshito appeared

medicines would have similar effects on loss ofin 1–2 months. A patient who could barely eat school

appetite caused by MPH or ATX.

lunch was soon able to eat more than half with

MPH suppresses hyperactivity and impulsivity,

The crude products of rikkunshito are ginseng,

improvement in appetite. Once patients adapted to

Atractylodis Rhizoma, Poria, licorice, Pinelliae Tuber,citrus unshiu peel, ginger, and Zizyphi Fructus, and
it is combined with shikunshito and nichinto. In

the environmental changes and the temperature
discontinue

Kampo

medicineandthoseaddition to the digestion and food absorption effects

frequently

forgotto

their

medicationof shikunshito, rikkunshito has the effects ofdiscontinued use within 2 months. The 3 patients

Pinelliae Tuber and therefore suppresses nausea

who continued Kampo medication for 4–10 months

and vomiting due to fluid retention in the stomach

continued to eat smaller school lunches, as did

and the effects of Citri Unshiu Pericarpium, which

patients who were picky eaters. In these individuals,

reduces gastric fluid retention and sputum. Similar

Kampo was continued over time. One patient

to shikunshito, rikkunshito also tonifies qi. It is used

continued taking shikunshito for 9 months. In thisto treat fatigue, nausea, loss of appetite, chronic

case, his appetite completely recovered to the extent

gastritis, and symptoms of gastroptosis. rikkunshitothat he consumed more than 1 serving of school

enhances appetite and gastrointestinal motility bylunch, but because Kampo medication helped him

became cooler, those patients who wanted toits antagonistic effects on serotonin 2 receptors. A12The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

takewhoVolume 13, Number 3 | Fall 2018

stay calm, administration was continued. Soon afterSummary
Whenthat, his MPH dose was reduced.

rikkunshito

shikunshito

orwasRegarding the time when Kampo medicines wereadministered for loss of appetite secondary toinitiated, 14 cases (70%) started during summer ortreatment with ADHD medicine, 16 out of 20 cases

fall when practices for field day were being held. In

showed improvement. In addition, among the 16

these cases, loss of appetite may have been caused

cases that showed improvement, 10 cases were ablebyandto finish taking Kampo medicines within 2 months.

increased humidity as well as deterioration of ADHD

There was no case in which ADHD medicine had tosymptoms due to changes in school–life rhythm.

be discontinued due to persistent loss of appetite.

higherenvironmental

temperatures

There were many cases in which continuing
medication was difficult due to the developmental

The abstract of this paper was presented at the 45th

characteristic of “inattention.” In 12 cases (60%),

Japan Pediatric Oriental Medicine Society Annual

despite being instructed to take medication twice perMeeting (Nagoya, 2017).

day, before breakfast and dinner, patients wereactually taking only 1 dose per day in the morning.

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The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

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