Stimulant Therapy of ADHD and Substance Abuse
From MindLinc Wiki
Premise: There is good evidence that pharmacological treatment of ADHD with stimulants (mainly methylphenidate and amphetamine) is highly effective. Many people, however, are concerned that treatment with these drugs may lead to higher incidence of later substance abuse.
Methods: Systematic review of all published longitudinal studies of ADHD children that measure prevalence of substance abuse during adolescence/adulthood. Random-effects metaanalysis (method of Carlin) was used to calculate the pooled estimate of all the odds ratios. This method weighs each study according to the number of subjects. To see if small-study bias was present, the method of Egger was used, i.e. regressing the standard normal deviate (SND) of the OR against the precision of the OR. In the absence of bias, these should run through the same origin. Small studies have low precision, large standard error, and therefore small SND, whereas large studies have higher precision, smaller standard deviations, and therefore large SND. Since these are naturalistic studies, baseline severity was also assessed (severe cases are more likely to be treated; severe cases may also be more susceptible to becoming substance abusers).
Validity: 1) Systematic review of RCT: no, 2) hand-searched journals: no, 3) bias towards positive trials taken into account: yes (but see below), 4) similar trend in all studies: no, 5) can they explain this heterogeneity: somewhat, 6) did they analyze individual data: yes
Results: 6 studies (5 prospective and 1 retrospective). 674 treated and 360 untreated subjects. Pooled OR was 1.9 for all substance abuse. NNT to prevent EtOHism was S and to prevent illicitdrug use, 16. There was a stronger protective effect in the studies with similar baseline severity; in fact, in the two studies that showed a deleterious effect of stimulant treatment, the non-treated group had more severe ADHD at baseline (per the authors; I did not look at individual studies). The method of Egger showed that no small-study bias could account for the effect.
| Study | Rx+ | Rx- | EtOH/+ | EtOH/- | NNT/H | Drug/+ | Drug/- | NNT/H |
|---|---|---|---|---|---|---|---|---|
| Lambert | 93 | 81 | 44% | 32% | 8 (H) | 25% | 21% | 25(H) |
| Biederman | 145 | 45 | 21% | 68% | 2 (T) | 16% | 42% | 4 (T) |
| Huss | 98 | 21 | 33% | 33% | -- | 32% | 29% | 33 (H) |
| Loney | 182 | 37 | 27% | 56% | 3 (T) | 17% | 19% | 50 (T) |
| Molina | 53 | 73 | 4% | 21% | 6 (T) | -- | 28% | 5 (T) |
| Barkley | data | not | available | for | me | to | look | at |
Remarks: No randomized trials. Baseline severity was similar in studies that showed a protective effect, but there are many other factors. How good is the "method of Egger" to rule out smallstudy bias? The studies included in this paper were all about the same size (N range was 119-219) -> is this method still applicable? What about non-English studies?
Bottom-line: Impossible to conclude that stimulant treatment protects against substance abuse. Likely that stimulant treatment does not cause a large increase in substance abuse. Therefore, harm-benefit ratio is probably in favor of benefit, since stimulants help ADHD kids function.
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