Detail Research Data

Data Doctoral/PhD
Research Title The Effect of Long-Acting Methylphenidate 20 mg Toward Dopaminergic Neurotransmission Enhancement and Clinical Symptoms Improvement in Children with ADHD. Study by Using Magnetic Resonance Spectroscopy Imaging
Kaji Etik Pass Number 4075
Kaji Etik Pass Date 17 Desember 2007
Focus Others (-)
Principal Investigator Tjhin wiguna
Promotor Prof.dr. Sasanto Wibisono SpKJ(K)
Co Promotor R Susworo
Co Promotor Prof.Dr.dr. Sudigdo Sastroasmoro SpA(K)
Departement Psychiatry
Category Clinic
Research Date 17 Desember 2007
Research Object Manusia
Fund Source Mandiri
Level Penelitian Doctoral/PhD


Background: Attention-deficit/hyperactivity disorder (ADHD) is a serious public mental health issue with diverse negative outcomes. Children with ADHD do not perform well at home nor in school. The present theory of ADHD is that; there is a dysregulation of dopamine (DA) neurotransmission with. a consequent dysregulation of DA-modulation in the fronto-striatocortical area. Treatment with methylphenidate leads to improved clinical symptoms of ADHD.

Objectives: (1) To analyze the effect of 12 weeks administration of long-acting methylphenidate 20 mg in prefrontal cortex, anterior cingulated gyrus, nucleus accumbens, globus pallidus, and amygdala, in either the right or the left hemisphere by using 1H magnetic resonance spectroscopy; (2) to analyze the effect of 12 weeks administration of long-acting methylphensdate 20 mg and the effect of terminating the medication for 1 month on pattern of clinical symptoms of ADHD.

Method: This was a prospective study with one group using pretest and posttest design. evaluate the response of DA neurotransmission to long-acting methylphenidate 20 mg. Time series design was performed to evaluate the pattern of change of clinical symptoms of ADHD during the 12 weeks administration of long-acting methylphenidate 20 mg and one month after terminating the medication by using the Indonesian hyperactive behavior assessment scale for kid (SPPAHI).ADHD was diagnosed based on DSM-IV TR criteria by using MINU for kid structured interview guideline. We examinated 21 children with ADHD, ages 7 to 10 years old, who were drug-naive acid had no other co-morbidity. A low time-echo (TE) MRS scan sampled voxels, of interest (1.5 x 1.5 x 2.0 cm) in prefrontal cortex, anterior cingulated gyrus, nucleus accumbens, globus pallidus, and amygdala in right and left hemispheres in all subjects. Compounds visualized with MRS included N-acetyl-aspartate (NAA), glutamate (Glu), creative (Cr), choline (Cho) and myo-inositol (mI). A paired t-test and Wilcoxon- Rank test was used to analyze the mean difference of the NAA/Cr, Glu/Cr, Cho/Cr and mI/Cr ratios. Standardized mean effect size (d) was also calculated. Parents filled out the Indonesian Child Hyperactivity Behavior Assessment Scale (SPPAHI) every two weeks. A repeated measures test was used to analyze the data.

Results: After the subjects took long-acting methylphenidate 20 mg for 12 weeks, there was a significant decrease in the Glu/Cr ratio in all areas examined (p<0.05); Cho/Cr ratio was significantly decreased in right and left prefrontal cortex, right anterior, cingulated gyrus, and right globus pallidus (p<0.05); ml/Cr ratio was decreased in the left prefrontal cortex and right anterior cingulated gyms (p<0.05); NAA/Cr ratio was increased significantly, except in left anterior cingulated gyrus, left globus pallidus, right and left amygdala (p>0.05). All standardized mean effect sizes ranged between 0.1 - 1.2 (d>0). A significant decreased in the SPPAHI score was reported by the parents while the child took the long-acting methylphenidate 20 mg for 12 weeks (p<0.001) and after the medication was discontinued for one month (p<0.05).

Conclusions: These findings suggest that administering long acting methylphenidate 20 mg for 12 weeks is associated with enhancement of dopaminergic neuro­transmission in fronto-striatocortical areas. Dopaminergic neurotransmission enhancement is also associated with reduced ADHD symptoms during the administration of the medication and persist one month after the medication was discontinued.