Methylphenidate DAT binding in adolescents with Attention-Deficit/ Hyperactivity Disorder comorbid with Substance Use Disorder--a single photon emission computed tomography with [Tc(99m)]TRODAT-1 study.
BACKGROUND
Attention-Deficit/Hyperactivity Disorder (ADHD) is highly prevalent among adolescents with Substance Use Disorders (SUD). Effects of methylphenidate (MPH) on ADHD are attributed to its properties of blocking the dopamine transporter (DAT) in the striatum. However, it has been demonstrated that drug addiction is associated with dopaminergic system changes that may affect MPH brain effects, emphasizing the need to better understand MPH actions in subjects with ADHD+SUD.


OBJECTIVE
To evaluate the effect of an extended release formulation of MPH (MPH-SODAS) on DAT availability in 17 stimulant-naive ADHD adolescents with comorbid SUD (cannabis and cocaine).


METHODS
Subjects underwent two single photon emission computed tomography (SPECT) scans with [Tc(99m)]TRODAT-1, at baseline and after 3 weeks on MPH-SODAS. Clinical assessment for ADHD relied on the Swanson, Nolan and Pelham Scale - version IV (SNAP-IV). Caudate and putamen DAT binding potential (BP) was calculated.


RESULTS
After 3 weeks on MPH-SODAS, there was a significant reduction of SNAP-IV total scores (p<0.001), and approximately 52% reductions of DAT BP at the left and right caudate. Similar decreases were found at the left and right putamen (p<0.001 for all analyses).


CONCLUSIONS
This study shows that the magnitude of DAT blockade induced by MPH in this population is similar to what is found in ADHD patients without SUD comorbidity, providing neurobiological support for trials with stimulants in adolescents with ADHD+SUD, an important population excluded from studies.
Szobot
Claudia M
CM
ADHD Outpatient Clinic, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre (POA), Estado do Rio Grande do Sul (RS), Brasil. cmszobot@terra.combr
Shih
Ming Chi
MC
Schaefer
Thais
T
Júnior
Neivo
N
Hoexter
Marcelo Q
MQ
Fu
Ying Kai
YK
Pechansky
Flávio
F
Bressan
Rodrigo A
RA
Rohde
Luis A P
LA
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications* / Q000000981:diagnostic imaging / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D003627:Data Interpretation, Statistical; D017831:Diagnosis, Dual (Psychiatry); D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008774:Methylphenidate / Q000378:metabolism*; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism; D015609:Organotechnetium Compounds; D011485:Protein Binding; D011569:Psychiatric Status Rating Scales; D019275:Radiopharmaceuticals; D019966:Substance-Related Disorders / Q000150:complications* / Q000000981:diagnostic imaging / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D014326:Tropanes; C104196:technetium Tc 99m TRODAT-1; D008774:Methylphenidate