Value of 99mTc-TRODAT-1 SPECT to predict clinical response to methylphenidate treatment in adults with attention deficit hyperactivity disorder

Abstract

In a previous study, binding of Tc-TRODAT-1 to the dopamine transporter (DAT) was found to be higher in patients with attention deficit hyperactivity disorder (ADHD) as compared to healthy controls. To determine whether the degree of Tc-TRODAT-1 binding to the striatal DAT may have a predictive role on the response to methylphenidate (MPH) in patients with ADHD. Twenty-two adult patients suffering from ADHD underwent a brain SPECT scan with Tc-TRODAT-1. After the scan patients received MPH, individually medicated up to 60 mg.day. Severity of illness was estimated using the Clinical Global Impression (CGI-S) Scale before treatment. Ten weeks after the beginning of MPH treatment the improvement in global symptoms was rated by the Clinical Global Improvement Scale (CGI-I). Before treatment 17/22 patients with ADHD presented with higher striatal DAT binding as compared to age-matched healthy controls (+23.8%; P<0.01). After treatment with MPH a significant improvement of ADHD symptoms was demonstrated by the CGI-I in 16 of these 17 patients (CGI-S before: 4.8; CGI-I after MPH: 1.9; P<0.01). Five patients showed reduced DAT binding prior to therapy (-14.4%; P=0.04); these patients did not respond to MPH therapy (CGI-S before: 4.5; CGI-I after MPH: 4.2; P=0.40). Our findings suggest that ADHD patients with primarily elevated binding of Tc-TRODAT-1 to the striatal DAT responded better to therapy with MPH as compared to those with normal or low DAT binding. Consequently, our results - even if obtained on a small collective indicate that measurement of DAT may be an important prognostic predictor for therapy response to MPH.