The results from this 11-week randomized, double-blind, placebo-controlled trial suggest that using OROS-MPH, relative to placebo, to treat ADHD did not improve smoking outcomes in adult smokers with ADHD participating in smoking cessation treatment (i.e., nicotine patch and counseling). There might be several reasons for this lack of significant effect. First, all participants were provided with the nicotine patch, which has been found to be effective for both smoking cessation40
and for ameliorating inattention symptoms;7,12,13
thus, the lack of OROS-MPH effect might reflect a ceiling effect. The abstinence rates--43% for prolonged abstinence and 39% for point-prevalence abstinence--would appear to be sufficiently low, however, to allow the demonstration of a treatment effect if one were present. Alternatively, the lack of effect might, in fact, reflect a true lack of medication effect. While the self-medication hypothesis might account for the observed differences between ADHD and non-ADHD individuals in smoking onset3
as well as the potential protective effects of stimulant medication in preventing the onset of smoking in individuals with ADHD,15
it might be that, once an individual becomes nicotine dependent, the dependence itself is the primary factor determining outcome as opposed to the factors that initially led to dependence.
Past research suggests that smokers with ADHD have more difficulty quitting smoking compared to smokers without ADHD.4,41
The present trial did not include a non-ADHD comparison group and, thus, we are unable to directly address the relative efficacy of the nicotine patch and counseling in our ADHD sample relative to a non-ADHD sample. However, to provide a context for our results, it is helpful to compare the present abstinence rates to those from nicotine patch trials completed in study samples not selected on ADHD status. A meta-analysis evaluating the efficacy of the nicotine patch revealed that the abstinence rate, generally defined as point-prevalence abstinence, for trials using the nicotine patch for 8 weeks or less was 37.9% on average.42
This rate is comparable to the point prevalence abstinence rate in the present trial which was 39% after 6 weeks of nicotine patch treatment. It is thus possible that the ADHD participants in the present trial did not experience greater difficulty in quitting smoking when treated with nicotine patch and counseling relative to non-ADHD individuals.
From a public health perspective, the key finding from the present study was that OROS-MPH, relative to placebo, was effective and safe in treating ADHD in adult smokers. In the present trial, 71% of OROS-MPH participants had a clinically meaningful decrease in symptoms (i.e., a decrease of at least 30%), a rate comparable to that reported for prior MPH trials conducted with samples not selected for smoking. The 44% treatment response rate in the placebo group was somewhat high but is consistent with the 39% placebo response rate reported by Biederman et al.22
Thus, neither smoking nor smoking cessation treatment appeared to decrease the effectiveness of OROS-MPH in treating ADHD.
The safety profile of OROS-MPH in the present trial, in which it was used in combination with the nicotine patch in smokers, is similar to that observed in two large clinical trials of OROS-MPH in adults with ADHD.22,23
Similar to the findings from these prior trials, OROS-MPH, relative to placebo, was associated with statistically significant, but relatively small, increases in blood pressure and heart rate. In the present study, there was no significant treatment group difference for the number of participants experiencing a clinically significant elevation of heart rate while there was a non-significant trend for more OROS-MPH participants to have clinically significant elevations in blood pressure; patients on OROS-MPH should have their blood pressure and heart rate monitored as recommended in the prescribing information for OROS-MPH. The TEAEs occurring at a significantly greater rate in OROS-MPH (decreased appetite, dyspepsia, psychomotor hyperactivity, heart rate increase, and heart palpitations) have been associated with OROS-MPH in previous trials.22,23
In the present trial, 5.5% of OROS-MPH, and 1.5% of placebo participants were permanently discontinued from OROS-MPH/placebo, rates comparable to that of Medori et al. 23
and lower than that of Biederman et al.22
The latter difference is likely due to higher doses used by Biederman et al.22
(1.3 mg/kg/day). The present findings also indicate that the 72mg/day OROS-MPH dose was generally well tolerated and that OROS-MPH did not significantly affect tolerability of the 21 mg/day nicotine patch. In comparing the present safety results to those of prior trials,22,23
it is important to note that the vital signs eligibility criterion utilized in the present trial was likely more restrictive than the criterion used in prior trials and, thus, may underestimate risks that might arise if OROS-MPH were used in smokers with higher baseline blood pressure and heart rate.
Evaluation of the second key safety concern, that OROS-MPH might increase, rather than decrease, smoking, revealed that both OROS-MPH and placebo participants decreased their CPD during both the pre- and post-quit phases of the trial and that this decrease was to a statistically greater degree in the OROS-MPH, relative to placebo, group during the post-quit phase. This finding is not consistent with laboratory findings that IR-MPH significantly increases smoking in adult smokers without ADHD who are not trying to quit smoking.27, 28
Several critical differences between the laboratory studies and the present study, including the MPH formulation and study population, might account for the discrepant findings. In addition, it should be noted that the effects of acute dosing observed in laboratory studies do not necessarily predict a medication’s effects when used in on-going treatment. A prime example of the differing effects associated with acute and chronic dosing is bupropion, which was found to increase smoking in a laboratory study43
, but which is an FDA-approved smoking cessation treatment.44
The results of the present trial suggest that the clinical use of OROS-MPH will not increase the daily smoking rate in adult smokers with ADHD who are interested in quitting smoking.
The present study had several strengths. First, this trial utilized a randomized, double-blind, placebo-controlled design, the gold standard in clinical trials. Second, study retention was high, with 84.3% of participants completing the 11-week active study phase. Third, compliance with taking OROS-MPH/placebo was high, with an average of 94% of prescribed pills taken. A final strength is that the study was conducted at sites that were geographically diverse as well as diverse in expertise, with two sites having expertise in smoking cessation trials, two sites with expertise in ADHD trials, and two sites with expertise in neither area; this diversity helps to ensure the generalizability of the results. One weakness of the present study was the somewhat restrictive eligibility criteria utilized, including the restrictive vitals signs criterion and the DSM-IV exclusions, including current abuse or dependence for a substance other than nicotine; thus, the present sample may not be representative of adult smokers with ADHD.
In conclusion, the use of OROS-MPH to treat ADHD did not significantly improve smoking outcomes in adult smokers with ADHD participating in smoking cessation treatment (i.e., nicotine patch and counseling), counter to our hypothesis. It did not worsen smoking outcomes, however, as might be predicted from human laboratory findings that IR-MPH increases smoking in smokers without ADHD.27,28
Results from the present trial suggest that OROS-MPH was safe and generally well tolerated by this sample of healthy adult ADHD smokers and effectively treated ADHD, a relatively common mental health condition, which left untreated, can result in significant impairment in nearly every area of functioning.