The Effect of Methylphenidate on Neurological Soft Signs in ADHD

Igor Ondrejka,Igor Hrtanek,Ingrid Tonhajzerova,Eva Snircova,Tomas Kulhan,Ivan Farsky,Gabriela Nosalova 대한신경정신의학회 2015 PSYCHIATRY INVESTIGATION Vol.12 No.4

ObjectiveaaNeurological soft signs are very common in children with the attention deficit hyperactivity disorder (ADHD), and the first line medication of this disorder is methylphenidate. The aim of the study was to assess the effect of methylphenidate on the neurological soft signs in children and adolescents suffering from ADHD depending on the dose of methylphenidate. MethodsaaThirty five patients with ADHD were investigated by the ADHD RS-IV parent version questionnaire and the Revised Neurological Examination for Subtle Signs before treatment adjustment and after four weeks of methylphenidate medication. The changes in hyperactivity symptomatology, neurological soft signs during therapy and the influence of the methylphenidate dose were statistically analyzed. ResultsaaA significant decrease in hyperactivity symptomatology was found after one month of methylphenidate medication (p= 0.0001) and significant decrease in neurological soft signs was demonstrated in 21 from a total of 26 items (p<0.05). Correlation analysis showed no relationship between the dose of methylphenidate and the improvement of neurological soft signs. Similarly, the improvement of ADHD symptomatology had not correlation with the improvement of neurological soft signs. ConclusionaaThe study demonstrated the positive effect of methylphenidate on neurological soft signs in which improvement occurred independently of the dose, indicating that their progress may be due to methylphenidate treatment of any dose. The unrelated effect of methylphenidate on the attention deficit hyperactivity disorder and neurological soft signs suggest that methylphenidate might be useful in the therapy of clumsy child syndrome and in ADHD treatment of non-responders.

ADHD 아동에서 나이, 지능, 용량 및 불안 증상에 따른 Oros-Methylphenidate 임상효과의 차이

배대석(Dai Seg Bai),서완석(Wan Seok Seo),송창진(Chang Jin Song),정철호(Chul Ho Jung),최상용(Sang Yong Choi),정성훈(Sung Hoon Jeong),이종훈(Jong Hun Lee),정운선(Un Sun Chung) 대한생물치료정신의학회 2006 생물치료정신의학 Vol.12 No.2

Objectives:This study evaluated the differences of Oros-methylphenidate effect of intellectual, cognitive and behavioral aspects in children with combined type of ADHD, according to age, intelligence level, dosage of Orosmethylphenidate and anxiety. Methods:Korean-Wechsler Intelligence Scale for Children-Ⅲ(WISC-Ⅲ) and computerized neurocognitive functions tests(CNT) and ADHD behavioral checklist by Swanson, Nolan and Pelham-Ⅳ(SNAP-Ⅳ) were performed initially and after four weeks of Oros-methylphenidate trial. All of the tests were compared according to age ranges, intelligence levels, dosage levels and degrees of anxiety. Results:The younger age group showed better improvement in commission errors in auditory and visual continuous performance test. The average intelligence group showed the best improvement while the least improvement was in the higher intelligence group. There were no differences of improvement according to dosage levels and there were no consistent findings according to the degree of anxiety either. Conclusions:In the younger age group of ADHD, methylphenidate may improve impulsivity related problems, so methylphenidate may also improve cognitive impulsivity in the younger children with ADHD as well as behavioral impulsivity. The average intelligence group of ADHD showed the best improvement and the lower intelligence group of ADHD also showed significant effect, that is partly because poorer performances in the initial test were improved by methylphenidate. In this study both levels of Oros-methylphenidate dosage were relatively higher than other studies so there were no differences between the lower and the higher dosage group. We should consider various factors such as age, intelligence level, internalizing symptoms when we try methylphenidate and it is recommended that a sufficient dose is better than a lowest effective dose. 목적 : 본 연구는 혼합형 ADHD 아동을 대상으로 Oros-methylphenidat를 4주간 지속적으로 투여한 후의 지적·인지적 개선효과가 나이, 지능 수준, 약물 용량, 불안 증상의 유무에 따라 어떤 차이가 있는 지 알아보기 위해시행되었다. 방법 : 대상 아동들은 Oros-methylphenidate를 투여하기 전 한국형 웩슬러 지능검사, 전산화 신경인지기능검사, SNAP-Ⅳ를 시행하였으며, 4주의 약물 치료 후 같은 검사를 반복하였다. 모든 결과들은 연령, 지능 수준, 용량, 불안의 유무에 따라 비교되었다. 결과 : 어린 아동군은 나이든 아동군에 비해 시각적·청각적 연속수행력의 오경보 오류에서 더 나은 향상을 보였으며, SNAP-Ⅳ를 통한 충동적 행동의 항목에서도 더 나은 향상을 보였다. 지능 수준에 따른 호전 정도에서는 평균수준의 지능군의 호전 정도가 가장 큰 반면, 높은 수준의 지능군의 향상 정도는 가장 작았다. 낮은 지능군의 시각적 연속수행력의 누락오류의 수, 선추적 검사 B에서의 오류의 수에서 가장 큰 호전이 관찰되다. Methylphenidate의 용량에 따른 증상 호전의 차이는 관찰할 수 없었으며, 불안의 정도에 따른 증상호전의 차이는 일관성이 없었다. 결론 : 어린 ADHD 아동은 행동적, 인지적 충동성과 연관된 문제들이 methylphenidate에 의해 더 많이 개선되었다. 평균지능의 ADHD 아동에서 가장 큰 호전이 있었으나, 낮은 지능군에서의 효과도 유의하였는데, 이는 낮은 지능군의 불량한 초기 수행이 methylphenidate로 개선되었기 때문이다. 용량, 불안 유무에 따른 치료 반응의 일관되지 않으며 추후 지속적인 연구가 필요하다. ADHD 아동에 대한 약물 치료시 나이, 지능수준, 내면화 증상 등과 같은 요인들을 고려해야 하며, 어린 나이에 충분한용량을 사용할 경우 더 나은 효과를 기대할 수 있다.

I-123 IPT SPECT를 이용한 주의력결핍 과잉행동장애 아동에서의 methylphenidate 투여 전후의 기저 신경절 도파민 운반체 밀도 변화 측정

류원기,김태훈,유영훈,윤미진,천근아,지대윤,김종호,최태현,이종두 대한핵의학회 2003 핵의학 분자영상 Vol.37 No.4

목적 : 주의력결핍 과잉행동장애 (Attention Deficit Hyperactivity disorder : 이하 ADHD)는 도파민계의 이상 기능으로 생기는 대표적 소아정신과 질환이다. Methylphenidate는 dopamine transporter(DAT)를 차단함으로써 ADHD 증상을 호전시키는 약물로 널리 알려져 있다. 따라서 본 연구에서는 ADHD 아동들을 대상으로 I-123 IPT SPECT를 이용하여 methylphenidate 투여 전후의 DAT density 양상을 비교해 보고자 한다. 대상 및 방법 : 연구대상은 9명의 ADHD 아동과 7명의 정상 대조군이었다. ADHD 아동군과 정상 대조군에 모두 약물 비노출 상태에서 [^(123)I]IPT를 정맥 주사후 2시간이 경과한 상태에서 SPECT를 촬영하였다. 이후 ADHD 아동군을 대상으로 methylphenidate 0.7mg/kg/d을 투여한 후 약 8주가 경과한 상태에서 [^(123)I]IPT SPECT를 재활영 하였다. Methylphenidate 투여 전화 후의 좌,우측 기저 신경절 DAT 특이결합/비특이결합 비율을 구한 뒤 비교하였고, 약물 투여 후의 ADHD 증상 척도로 측정한 증상 호전도와 좌,우측 기저 신경절 DAT 특이결합/비특이결합 비율 변화사이의 상관관계를 알아보았다. 결과 : ADHD 아동군에서 약물 비노출 상태와 정상 대조군 사이의 좌, 우측 기저 신경절 DAT 특이결합/비특이결합 비율을 비교한 결과 DAT 결합 비율이 정상 대조군에 비해서 유의하게 증가되었다(Right : z=2.057, p=0.041 ; Left : z=2.096, p=0.032). 또한 ADHD 아동들에세 methylphenidate 투여 전과 후 상태에서의 기저 신경절 DAT 특이결합/비특이 결합 비율을 비교한 결과, methylphenidate 투여 후 상태가 methylphenidate 투여 전 상태에 비해 좌, 우측 DAT 결합비율이 유의하게 낮아진 것을 관찰 할 수 있었다 (우측 : t=3.239, p=0.018 : 좌측 : t=3.133, p=0.020). ADHD 증상의 호전도와 좌,우측 기저 신경절 DAT 특이결합.비특이결합 비율 변화사이에는 유의한 상관관계를 보이지 않았다. 결론 : 이러한 결과는 주의력결핍 과잉행동장애의 치료제인 methylphenidate가 작용하는 기전을 이용하여 주의력결핍 과잉행동장애의 병태생리와 연관된 도파민계 기능이상 가능성을 지지한다고 생각된다. Purpose : attention deficit hyperactivity disorder (ADHD) has been known as psychiatrio disorder in childhood associated with dopamine dysregulation. In present study, we investigated changes in dopamine transporter (DAT) density of the basal ganglias using [-123 N-(3-iodoproper-2-yl]-2-carbomethoxy-3beta-(4-chlorophenyl) tropane [l-123 IPT] SPECT in children with ADGD before and after methylphenidate treatment. Materials and Method : Nine drug-naive children with ADGD and seven normal children were included in the study. We performed brain SPECT two hours after the intravenous administration of l-123 IPT and made both quantitative and qualitative analyses using the obtained SPECT data, which were reconstructed for assessment of specific/nonspecific DAT binding ratios in the basal ganglia. All children with ADGD reperformed [123]IPT SPECT after treatment with methylphenidate(0.7mg/kg/d) during about 8 weeks. SPECT data reconstructed for the assessment of specific/nonspecific DAT binding ration of the basal ganglia were compared between before and after treatment methylphenioate. We investigated correlation between the change of ADHD symptom severity assessed with ADHD rating scale-IV and specific/nonspecific DAT binding ratio of the basal ganglia comparing to normal children (Right : z - 2.057, p = 0.041 : Left : z = 2.096, p = 0.032). Under treatment with methylphenidate in all chkildren with ADHD, specific/nonspecific DAT binding ration of both basal ganglia decreased significatnly greater than before treatment with methyphenidate (Right 1 = 3.239, p = 0.018, Left : t =3.133, p = 0.020). However no significant correlation between the change of ADHD symptom severity scores and specific/nonspecific DAT binding ratio of the basal ganglia ere for support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD.

주의력결핍 과잉행동장애 아동에서 Methylphenidate 투여 전후 [123I]IPT SPECT로 측정한 기저 신경절 Dopamine Transporter Density

천근아,유영훈,남궁기,김찬형,이종두 대한신경정신의학회 2003 신경정신의학 Vol.42 No.1

Objectives:ADHD has been known as psychiatric disorder in childhood associated with dopamine dysregulation. The symptoms of ADHD can be treated with methylphenidate, a potent blocker of the dopamine transporter (DAT). In present study, we investigated DAT density using I-123N-(3-iodopropen-2-yl)-2β-carbomethoxy-3beta-(4-chlorophenyl) tropane ([123I]IPT SPECT) in children with ADHD before and after treatment with methylphenidate. Methods:Seven drug-naive children with ADHD and eight normal children were included in the study and performed SPECT 2 hours after an intravenous administration of [123I]IPT. All children with ADHD reperformed [123I]IPT SPECT after treatment with methylphenidate (0.7 mg/kg/d) during about 8 weeks. SPECT data reconstructed for the assessment of specific/ nonspecific DAT binding ratio of the basal ganglia were compared between before and after treatment methylphenidate. We investigated correlation between the change of ADHD symptom severity assessed with ADHD rating scale-IV and specific/ nonspecific DAT binding ratio of basal ganglia. Results:Children with ADHD had a significantly greater increase of specific/nonspecific DAT binding ratio of right basal ganglia than normal children (Right:z=2.085, p=0.037;Left:z=1.506, p=0.132). Under treatment with methylphenidate in all children with ADHD, specific/nonspecific DAT binding ratio of both basal ganglia decreased significantly greater than before treatment with methylphenidate (Right:t=3.239, p=0.018;Left:t=3.133, p=0.020). However, no significant correlation between the change of ADHD symptom severity scores and specific/nonspecific DAT binding ratio of the basal ganglia were found. Conclusions:The data of this study using methylphenidate in children with ADHD support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD

주의력결핍 과잉행동장애 아동에서 Methylphenidate 투여 전후[¹²³I]lPT SPECT로 측정한 기저 신경절 Dopamine Transporter Density

천근아,유영훈,남궁기,김찬형,이종두 大韓神經精神醫學會 2003 신경정신의학 Vol.42 No.1

Objectives: ADHD has been known as psychiatric disorder in childhood associated with dopamine dysregulation. The symptoms of ADHD can be treated with methylphenidate, a potent blocker of the dopamine transporter (DAT). In present study, we investigated DAT density using I-l23N- (3-iodopropen-2-y1) -2β-carbomethoxy-3beta- (4-chlorophenyl) tropane ([¹²³I)] IPTSPECT)in children with ADHD before and after treatment with methylphenidate. Methods : Seven drug-naive children with ADHD and eight normal children were included in the study and performed SPECT 2 hours after an intravenous administration of [¹²³I] IPT. All children with ADHD reperformed [¹²³I]IPT SPECT after treatment with methylphenidate (0.7 mg/kg/d) during about 8 weeks. SPECT data reconstructed for the assessment of specific/nonspecific DAT binding ratio of the basal ganglia were compared between before and after treatment methylphenidate. We investigated correlation between the change of ADHD symptom severity assessed with ADHD rating scale-IV and specific/nonspecific DAT binding ratio of basal ganglia. Results : Children with ADHD had a significantly greater increase of specific/nonspecific DAT binding ratio of right basal ganglia than normal children (Right : z=2.085, P=0.037 ; Left : z =1.506, P =0.132). Under treatment with methylphenidate in all children with ADHD, specific/nonspecific DAT binding ratio of both basal ganglia decreased significantly greater than before treatment with methylphenidate (Right : t=3.239, p=0.018 : Left : t=3.133, P=0.020). However, no significant correlation between the change of ADHD symptom severity scores and specific/nonspecific DAT binding ratio of the basal ganglia were found. Conclusions : The data of this study using methylphenidate in children with ADHD support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD.

Differences in Utilization Patterns among Medications in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: a 36-Month Retrospective Study Using the Korean Health Insurance Review and Assessment Claims Database

방수영,황준원,곽영숙,정유숙,이소영,김봉석,손석한,정운선,양재원,홍민하,반건호,최형윤,오인환,이연정 대한의학회 2016 Journal of Korean medical science Vol.31 No.8

We evaluated the differences in utilization patterns including persistence and adherence among medications in children and adolescents with attention deficit hyperactivity disorder (ADHD). The current study was performed using data from the Korean Health Insurance Review and Assessment claims database from January 1, 2009 to December 31, 2013. Our study sample consisted of 10,343 children and adolescents with ADHD who were not given their newly prescribed medication in 360 days before the initial claim in 2010. Data were followed up from the initiation of treatment with ADHD medications in 2010 to December 31, 2013. Discontinuation rates for 4 ADHD medications in our sample ranged from 97.7% for immediate-release methylphenidate to 99.4% for atomoxetine using refill gap more than 30 days and from 56.7% for immediate-release methylphenidate to 62.3% for extended-release methylphenidate using refill gap more than 60 days. In the number of discontinued, we found significant differences among medications using refill gap more than 30 days. Among 4 ADHD medications, extended-release methylphenidate and atomoxetine had more days than immediate-release methylphenidate and osmoticcontrolled oral delivery system methylphenidate. In logistic regression analyses, extendedrelease methylphenidate, osmotic-controlled oral delivery system methylphenidate, and atomoxetine showed less discontinuation compared to immediate-release methylphenidate group when a refill gap more than 30 days was used. In logistic regression analysis of adherence, we could not find any differences among 4 medication types. We suggest that the utilization patterns should be assessed regularly in order to improve future outcomes in children and adolescents with ADHD.

Methylphenidate에 의해서 유발된 주의력결핍-과잉행동장애 환자의 수면장애에 대한 Mirtazapine의 치료효과 : 증례 및 고찰

임명호(Myung Ho Lim),이우철(Woo Chul Lee),이상구(Sang Koo Lee),이창민(Chang Min Lee),김현우(Hyun Woo Kim),왕성근(Seong-Keun Wang) 대한생물치료정신의학회 2006 생물치료정신의학 Vol.12 No.2

주의력결핍-과잉행동장애(Attention Deficit Hyperactivity Disorder)는 소아청소년시기에 5~10%의 유병율을 갖고 있는 매우 흔한 질환이다. 주의력결핍-과잉 행동장애에서 임상적으로 가장 많이 사용되고 있는 methylphenidate는 과잉행동 및 주의력 개선에 70~85% 정도의 높은 증상 개선율을 갖고 있지만 반면에 수면장애, 식욕부진, 두통 등의 부작용을 호소하는 아동으로 인하여 임상적으로 어려움을 겪기도 한다. 한편 mirtazapine은 노르아드레날린과 세로토닌의 신경전달을 함께 강화하는 새로운 항우울제이며, 또한 mirtazapine은 히스타민 수용체와 아드레날린성 및 콜린성 수용체를 길항함으로써 우울장애에 함께 수반된 수면장애에도 효과가 있었음을 보고하는 외국사례가 있었다. 본 저자는 주의력결핍-과잉행동장애로 진단받은 6세 아동에서 methylphenidate 투여를 시작한 이후 이차적으로 발생한 수면장애에 대해서 항우울제인 mirtazapine을 투여하여 수면다원 검사상 서파수면의 증가 및 REM수면의 감소 등 객관적인 수면장애 증상 개선을 보였기에 이를 보고하고 문헌을 함께 고찰하고자 한다. Objectives:This case presents a 6 year-old-boy diagnosed with ADHD. The patient was hospitalized under the chief complaint of hyperactivity behavior and distracted inattention. A secondary sleep disorder was found after 10㎎ qd of methylphenidate was started, administering mirtazapine revealed improvement of sleep disorder. Case:On July 9 2005, the child was hit by a small vehicle on the road between his apartment and a shopping mall. After this accident a child was referred for treatment of hyperactivity and distractibility. After adding 10mg qd of methylphenidate IR, his PSQI global score was 9 and his ISI total score was 15 which are consistent with moderate stage of insomnia. Polysomnography was performed to detect the objective sleep disorder. As a result of the increase of REM sleep and the decrease of REM latent period further investigation was carried out. From the 16th day of hospitalization 15㎎ of mirtazapine was given hs for a week. Soon after starting mirtazapine the child fell a sleep without whining time and his shouting were much improved. On a 7th day of mirtazapine administration, PSQI global score of 2 and ISI total score of 3 was noted which represented a significant improvement. Polysomnography was reperformed on the 10th day as a result the delay of REM latent period and the decrease of REM sleep as a normal range, The normalization of REM sleep rhythm and the increase of slow wave were objectively improved. Discussion:When methylphenidate is used in the treatment for ADHD, Clinical course shows a sleep disorder in 29~64% of ADHD subjects. mirtazapine(Remeron), the antidepressant, has an antagonistic effect for 5HT2a receptor and is recently used for its effect in the improvement of sleep disorder. The Author hereby report that mirtazapine objectively improves sleeping disorders which often results from giving methylphenidate in ADHD.

수면-각성 구조와 뇌파 파워에 대한 Modafinil 및 Methylphenidate의 영향

박정아,장환수,정성훈,하정희,이호원,이만기 대한정신약물학회 2009 대한정신약물학회지 Vol.20 No.4

Objective:Modafinil, methylphenidate, and caffeine are wakefulness-promoting substances. Previously, it was reported that caffeine-induced wakefulness differs from natural wakefulness in terms of the EEG spectral profiles. In order to evaluate whether wakefulness induced by other psychostimulants differs from both caffeine-induced and natural wakefulness, we examined the effects of the psychostimulants on sleep-wake architecture and EEG spectral profiles. Methods:Eighteen Sprague-Dawley male rats underwent an EEG/EMG recording session from 10:30 to 17:30. They received caffeine (7.5, 15, 30 mg/kg i.p.), methylphenidate (1, 2, 5, 10 mg/kg i.p.) or modafinil (5, 10, 25, 50, 100 mg/kg i.p.) at 13:30. The number, total duration, and average duration of sleepwake states were obtained. EEG band powers were calculated by spectral analysis. Frequency bands were divided into the following ranges:D1, 1-2.5 Hz;D2, 2.5-4.5 Hz;T1, 4.5-7 Hz;T2, 7-10 Hz;SI, 10-14 Hz;B1, 14-22 Hz;B2, 22-34 Hz;GA, 34-50 Hz. Results:All three psychostimulants significantly and dose-dependently increased active wake duration and decreased slow-wave sleep. Equipotent doses of caffeine, methylphenidate, and modafinil for increasing active wake and decreasing slow-wave sleep were 7.5 mg/kg, 10 mg/kg, and 100 mg/kg, respectively. In equipotent doses, an increase of active wake duration by caffeine and methylphenidate was attributed to increases of both frequency and average duration of active wake state, whereas increase of active wake duration by modafinil was attributed to increase of average duration of active wake state only. In equipotent doses, caffeine and methylphenidate decreased the power of lower frequency bands (1-22 Hz), whereas modafinil did not. During slow-wave sleep, modafinil and methylphenidate increased the power of lower frequency bands, but caffeine did not. All the psychostimulants increased the power of the GA band, which was more prominent in the frontal cortex than the parietal cortex. Conclusion:These results suggest that modafinil-induced wakefulness differs from caffeine- or methylphenidate-induced wakefulness in terms of EEG spectral profiles and sleep-wake architecture. 모다피닐, 메틸페니데이트와 카페인은 모두 각성 항진효과를 가지나 작용 기전은 다르다. 뇌파와 근전도를 이용하여 이들 세 가지 약물의 투여가 흰쥐의 수면-각성구조에 미치는 영향에 대하여 평가하였다. 카페인(7.5, 15, 30 mg/kg i.p.), 메틸페니데이트(1, 2, 5, 10 mg/kg i.p.) 또는 모다피닐(5, 10, 25, 50, 100 mg/kg i.p.)을 약 7일의 휴지기간을 통해 반복 투여하였다. 세 가지 약물 모두 용량의존적으로 활동각성(active wake) 기간을 증가시켰다. 활동각성 증가와 서파수면 감소 정도를 통한 동등 효과 용량은 카페인 7.5 mg/kg, 메틸페니데이트 10mg/kg, 모다피닐 100 mg/kg임을 알 수 있었다. 동등효과 용량에서 카페인과 메틸페니데이트의 활동각성 증가는 활동각성의 발생 횟수의 증가와 더불어 1회 발생시 평균 지속 기간이 증가된 데 따른 것이었으나, 모다피닐의 활동각성 증가에는 평균 지속 기간의 증가만이 관여하였다. 약물 투여 후 전체 기록 시간(4시간) 동안의 활동각성 발생 기간은 세 가지 약물 모두가 동일하나, 모다피닐과 메틸페니데이트가 투여 후 3시간이 경과하면서 활동 각성이 기준수치로 회복하는 데 비해 카페인은 그렇지 않았다. 각성 항진 동일효과 용량에서 카페인과 메틸페니데이트는 1~22 Hz 영역에 속하는 다소 낮은 뇌파밴드의 파워(power)값을 유의하게 감소시켰으나, 모다피닐의 경우 그렇지 않았다. 34~50 Hz 영역의 파워값은 세가지 약물 투여시 모두 유의적으로 증가하였으며, 이런 현상은 두정피질보다 전두피질에서 뚜렷하였다. 모다피닐과 메틸페니데이트 투여는 서파수면 동안 저주파수 영역의 밴드 파워를 증가시켰으나, 카페인 투여시에는 볼 수 없었다. 따라서 본 실험 결과 카페인과 메틸페니데이트에 의한 정량뇌파 양상이 모다피닐의 양상과 차이가 있고, 카페인에 의한 수면-각성 구조 변화는 메틸페니데이트와 모다피닐의 것과 차이가 있다.

주의력 결핍 과잉 운동장애에 대한 Methylphenidate의 임상 효과

사공정규,박형배,이종범 大韓神經精神醫學會 1994 신경정신의학 Vol.33 No.2

The objectives of this study were to evaluate the effect of methylphenidate on attention deficit hyperactivity disorder, using child attention problem checklist to 42(male : 29, female : 13) attention deficit hyperactivity disorder patients from March 1992 to February 1993. The results were as follows : There was significant improvement on symptoms in the scores rated by teachers in 7th & 28th day after methylphenidate administration compared to baseline score(p<0.05) and 28th day score showed significant improvement compared to 7th day scores(p<0.05). There was significant improvement on symptoms in the scores rated by parents in 28th day after methylphenidate administration compared to baseline score(p<0.05) and 28 th day score showed significant improvement compared to 7th day score. In single administration of methylphenidate in Sunday morning, there was significant improvement on symptoms in morning score compared to afternoon score(p<0.05). In the administration of methylphenidate of same dosage, the 7th day rating score of teacher showed significant improvement on symptoms compared to the Sunday morning rating score of parents(p<0.05) and the 28th day comparision was also showed signigicant improvement on symptoms in the scores rated by teachers compared to the scores rated by parents(p<0.05).

Abuse and dependence liability analysis of methylphenidate in the spontaneously hypertensive rat model of attention-deficit/ hyperactivity disorder (ADHD): what have we learned?

Ike Dela PENA,정재훈,한덕현,김붕년 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.4

Methylphenidate is the most prescribed stimulantmedication for attention-deficit/hyperactivity disorder(ADHD). Despite the well documented clinical benefits ofthe drug, several questions remain unanswered concerningthe effects of extended methylphenidate use (e.g. canmethylphenidate be abused by ADHD patients? doesrepeated methylphenidate treatment produce addiction?). Preclinical studies can help address the long-term safety ofclinical treatments, moreover animal studies providevaluable information on the details of drug actions. Thespontaneously hypertensive rat (SHR), bred from normotensiveWistar Kyoto rat strain, is considered as the bestvalidated and the most widely used animal model ofADHD. We reviewed the findings of research reports thatinvestigated the abuse and dependence liability of methylphenidatein SHR. In particular, we surveyed the studieswhich investigated the effects of methylphenidate pretreatmenton subsequent methylphenidate-induced conditionedplace preference or self-administration for they maygive insights into the abuse or dependence liability of longtermmethylphenidate treatment in ADHD.