Selegiline in ADHD adults: plasma monoamines and monoamine metabolites.
Plasma monoamines and monoamine metabolites were assessed before and during selegiline treatment in adults with attention deficit/hyperactivity disorder (ADHD). Selegiline, at low dose, is a selective monoamine oxidase inhibitor type B (MAOI-B). After 2-week placebo baseline, 36 ADHD adults were randomized to 6-week placebo or 20 mg/day or 60 mg/day selegiline, followed by 2-week posttreatment placebo. Twenty-seven subjects continued into a 6-week 20-mg/day or 60-mg/day selegiline period. Behavioral variables included self-rated scores on the Conners' Abbreviated Teacher Rating Scale (Conners-ATRS) and performance on a Continuous Performance Task (CPT). Plasma samples were assayed for amines (dopamine, norepinephrine, epinephrine), precursor (DOPA), and metabolites (HVA, DOPAC, DHPG, normetanephrine, metanephrine, 5-HIAA). Selegiline produced dose-dependent changes in monoamine metabolites and DOPA plasma levels. Dopaminergic indices were associated with ADHD symptom severity (Conners-ATRS) and noradrenergic indices with CPT performance. Serotonergic metabolism, challenged by selegiline, correlated with clinical changes. These findings support a multisystem dysfunction underlying ADHD pathophysiology.
Ernst
M
M
Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland, USA.
Liebenauer
L L
LL
Tebeka
D
D
Jons
P H
PH
Eisenhofer
G
G
Murphy
D L
DL
Zametkin
A J
AJ
D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology*; D015306:Biogenic Monoamines / Q000378:metabolism*; D004298:Dopamine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D009638:Norepinephrine / Q000097:blood; D011597:Psychomotor Performance / Q000187:drug effects; D012642:Selegiline / Q000009:adverse effects / Q000627:therapeutic use*; D012701:Serotonin / Q000097:blood
D015306:Biogenic Monoamines; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine