A prior secondary analysis of data from the same parent trial had indicated gefitinib mechanism of action the presence of a particular subgroup that could experience benefit from augmentation treatment with OROS-MPH, specifically, non-White smokers who showed higher rates of complete abstinence when treated with OROS-MPH than with placebo in contrast to their White counterparts who showed no superior effect of the active drug (Covey et al., 2010). The present analysis has suggested that ADHD-C smokers who are highly nicotine dependent comprise another subgroup likely to benefit from OROS-MPH treatment. The data also identified a subgroup for whom OROS-MPH is not a treatment of choice, that is, highly dependent ADHD-IN smokers who were found to do poorly with OROS-MPH but responded well to nicotine patch (and counseling) alone.
Neurobiological and other mechanisms underlying the contrasting clinical manifestations warrant further study. One implication of the divergence in response by ADHD subtype, relevant to the ongoing debate regarding the structure of ADHD (Coghill & Seth, 2011), is that qualitatively distinct clinical entities comprise the diagnosis. The inability of the continuous measure of ADHD symptoms at baseline to predict smoking abstinence argues against the alternative possibility that the ADHD subtypes represent points on a severity continuum. A second implication, relevant to smoking cessation treatment research, is that OROS-MPH offers targeted benefit for smokers with high nicotine dependence and other features that delineate the symptom structure of ADHD.
The rigorous study design and careful assessment of ADHD diagnosis and cessation outcome in the parent trial are strengths of the study. Limitations that call for cautious interpretation of findings include the use of selection factors in participant recruitment (including the exclusion of smokers with current substance use or other psychiatric disorders) and the post hoc and subgroup nature of the present analysis. The moderating effect of the FTND, observed post hoc, requires more investigation. The small numbers of non-White participants (n = 51) prevented a valid investigation of a potential impact of race/ethnicity. Smoking Cilengitide prevalence is higher and cessation lower among smokers with ADHD than among psychiatrically unaffected smokers, and smoking outcomes may differ according to the predominance of inattentive or hyperactive/impulsive symptoms. The present observations from a trial of OROS-MPH suggest that assessment of ADHD subtype and of nicotine dependence level comprise elements of a targeted personalized treatment approach for smokers with ADHD. More research to validate this implication and test its applicability to other nicotine-analog drugs is warranted.