Pharmacological cognitive enhancers: comment on Smith and Farah (2011)

Smith and Farah (2011) provided a thought-provoking and perhaps deliberately provocative literature review of the use of stimulants to improve cognitive functioning in humans. They addressed the apparently increasing willingness of individuals mostly in the United States to use stimulants for this purpose and then summarized published literature that explores whether stimulants actually improve specific aspects of neurocognitive function. Although calling for more research, they tentatively concluded that stimulants indeed may be "smart pills" for some people under certain circumstances. This comment emphasizes that they never actually defined the desired qualities of a smart pill, seemed to accept the unproven axiom that slight improvements in specific tests constitute meaningful enhancement of intelligence, and failed to consider the possible costs to individuals and to society of promoting the use of this class of medications for such a purpose.     

The impact of stimulants on a clinical measure of attention in children with ADHD.

The effect of stimulant medication on the attentional functioning of 23 children (8-12 yrs) with attention deficit/hyperactivity disorder (ADHD) was investigated. Significant main effects of medication and TEA-Ch subtests were found, however there was no significant interaction. Planned contrasts showed that stimulants improved performance on the sustained attention, but not the selective or divided attention, subtests. Similar to previous studies, the results indicate that stimulants improve sustained attention in children with ADHD. Significant effects of stimulants on selective and divided attention, however, were not as apparent. Therefore, care must be taken when using TEA-Ch subtests to assess performance change subsequent to stimulant administration.     

The impact of stimulants on a clinical measure of attention in children with ADHD

The effect of stimulant medication on the attentional functioning of 23 children (8–12 yrs) with attention deficit/hyperactivity disorder (ADHD) was investigated. Significant main effects of medication and TEA-Ch subtests were found, however there was no significant interaction. Planned contrasts showed that stimulants improved performance on the sustained attention, but not the selective or divided attention, subtests. Similar to previous studies, the results indicate that stimulants improve sustained attention in children with ADHD. Significant effects of stimulants on selective and divided attention, however, were not as apparent. Therefore, care must be taken when using TEA-Ch subtests to assess performance change subsequent to stimulant administration.     

Not Just “Study Drugs” for the Rich: Stimulants as Moral Tools for Creating Opportunities for Socially Disadvantaged Students

An argument in the cognitive enhancement literature is that using stimulants in populations of healthy but socially disadvantaged individuals mistakenly attributes pathology to nonpathological individuals who experience social inequalities. As the argument goes, using stimulants as cognitive-enhancing drugs to solve the social problem of poorly educated students in inadequate schools misattributes the problem as an individual medical problem, when it is really a collective sociopolitical problem. I challenge this argument on the grounds that not all types of enhancement have to be explained in medical terms, but rather at least one conception of enhancement can be explained in social terms—opportunity maintenance. Therefore, I propose that as a moral requirement we ought to explore whether stimulants could be a means of remedying underprivileged children's experiences of social inequalities that are borne from inadequate schools for the sake of increasing their chances for opportunities and well-being.     

Responses to methylphenidate in Attention-Deficit/Hyperactivity Disorder and normal children: update 2002

Since the positive effects of stimulants on disruptive behavior were described (Bradley & Bowen, 1941), further pediatric studyhas been limited almost exclusively to samples of hyperkinetic school-age children. Because these agents normally were viewed as arousing in their effects on the central nervous system, but were calming in their therapeutic effects on these children, stimulant effects on Attention Deficit Disorder (ADD) were interpreted as being 'paradoxical.' Investigation of effects in normal children and adolescents and in those with disorders unrelated to Attention-Deficit/Hyperactivity Disorder (ADHD), as well as in young adult samples, however, indicate that stimulants appear to have similar behavioral effects in normal and in hyperactive children. This brief report is an update (as of August 2002) on studies of stimulants in ADHD and normal children, with particular focus on MPH.     

Attention-Deficit Hyperactivity Disorder and Event-Related Potentials: Evidence for Deficits in Allocating Attentional Resources to Relevant Stimuli

Current research on the nature of attentional deficits in attention-deficit hyperactivity disorder (ADHD) is reviewed with a focus on studies using event-related potentials (ERPs). A robust effect is the smaller amplitude of the P3 wave to both auditory and visual stimuli for individuals with ADHD than for normal controls. This effect is indicative of deficits in the allocation of attentional resources to task-relevant information. The Nd wave is also smaller for individuals with ADHD, an effect that suggests impairments in the discrimination and preferential processing of task-relevant information, rather than distractibility by irrelevant stimuli. Studies of the effects of methylphenidate on ERPs in ADHD indicate that this stimulant enhances the quality of stimulus evaluation and speeds response time. These specific effects support the view that ADHD involves deficits in energetic processes that are required for processing task-relevant stimuli.     

Non-stimulant treatment of attention-deficit/hyperactivity disorder

Stimulants are a highly efficacious and safe treatment for attention-deficit/hyperactivity disorder (ADHD), with 75% to 90% of patients responding well if two different stimulants (amphetamine and methylphenidate) are used. Nonetheless, a subset of ADHD patients will either fail to respond to stimulants or have side effects that preclude their use (tics, severe loss of appetite, marked insomnia). For such patients, there are a number of non-stimulant agents that serve as second-line treatments. Tricyclic antidepressants (TCAs) are the most studied of these drugs. They are superior to placebo in the treatment of ADHD and may reduce abnormal movements in patients with ADHD/tic disorder. TCAs often produce side effects of sedation, dry mouth, and constipation. Bupropion is superior to placebo in the treatment of ADHD and has a more favorable side-effect profile than the TCAs. A new selective norepinephrine reuptake inhibitor, atomoxetine, has been shown to be efficacious in the treatment of ADHD and has recently received an approvable letter from the Food and Drug Administration. The a-agonists clonidine and guanfacine have also been used as alternative agents in ADHD, though the controlled data are more limited. A recent controlled clinical trial suggests a combination of methylphenidate and clonidine has advantages in the treatment of comorbid ADHD and tics over either medication alone. Clinical guidelines for each of these agents, as well as their use in combination with stimulants in comorbid conditions, will be discussed.     

The spontaneously hypertensive rat (SHR) as an animal model of childhood hyperactivity (ADHD): changed reactivity to reinforcers and to psychomotor stimulants.

Childhood hyperactivity (attention-deficit hyperactivity disorder, ADHD) is a behavior disorder affecting 2-6% of grade-school children. The main symptoms are attention problems and hyperkinesis. The disorder is commonly treated with psychomotor stimulants, usually methylphenidate hydrochloride (ritalin) or d-amphetamine. Neither the cause of the disorder nor the basis of the effectiveness of the drug treatment is well understood. Differences in reinforcement processes have been implicated as part of the underlying problem. The main purpose of the present research was to investigate reinforcement processes and motor characteristics with and without stimulant medication in SHR, as an animal model of ADHD, and WKY controls, its normoactive progenitor strain. SHR behavior turned out to be more sensitive to immediate reinforcement and proportionately less sensitive to delayed reinforcement when compared to the behavior of WKY, as demonstrated by systematic changes in rates of responding throughout fixed-interval schedules of reinforcement of bar-presses by water. The psychomotor stimulants weakened the control by immediate reinforcers and strengthened the control by delayed reinforcers, with the effect of the drugs being more pronounced in WKY than in SHR. The results are consistent with clinical observations that ADHD children are less willing than others to accept "delayed gratification" and that methylphenidate increases the control of delayed reward over their behavior.     

Correspondence between children's and adults' ratings of stimulant-induced changes in ADHD behaviours in a crossover trial with medication-naive children

Correspondence between children's and adults' ratings of changes in ADHD behaviours was investigated in a paediatric ADHD stimulant crossover trial. Thirty-one children completed an ADHD self-report scale each week, and comparisons were made with an ADHD questionnaire completed by adults (combined parent and teacher ratings). Children's and adults' ratings demonstrated good internal consistency, were significantly associated with the assessment of ADHD behaviours in the placebo condition and showed comparable responsiveness to stimulants at the group level. Furthermore, a large and significant correlation was detected between the two sets of informants' ratings of changes from placebo to both methylphenidate and dextroamphetamine high-dosage conditions, but not from placebo to low-dosage conditions. Agreement in the categorization of best stimulant condition for individual children was significant, but modest from a clinical perspective. The results indicate that children's ratings correspond adequately with adults' ratings, and thus appear to be a complementary outcome measure.     

Successful Child Psychotherapy of Attention Deficit/Hyperactive Disorder: An Agitated Depression Explanation

Science tries to explain phenomena in ways that are demonstrable and replicable to develop logical, coherent, parsimonious, and predictive theoretical systems. Yet hyperactive children are given stimulants to "calm" them down, despite the fact that science would predict stimulants would increase hyperactivity. Bradley (1937, 1950) observed that half of the behavior-problem children to whom he administered a stimulant for one week became subdued. He called this finding paradoxical, speculating that inhibitory centers of the central nervous system were stimulated. While Bradley's assertion of a paradoxical reverse effect in children may be an empirical observation, it is not an explanation. The Attention Deficit/Hyperactive Disorder (ADHD) is inferred to exist from hyperactive behavior, which in turn, is inferred to be neurological in origin, a circular argument. An inevitable consequence of the belief in the hypothetical neurological etiology of ADHD is that children are typically given stimulants. Using the case of a seven-year old child, described as experiencing ADHD, who was treated successfully without medication as an illustration, the author provides an alternative, more parsimonious explanation of the etiology, suggesting that ADHD is related to agitated depression.     

Sensation seeking, augmenting-reducing, and the perceived and preferred effects of drugs

The following measures were administered to 78 undergraduates: the General and Disinhibition subscales of Zuckerman's (1971) Sensation-Seeking Scale; the Reducer-Augmenter Scale (RAS; Vando, 1970, 1974); self-reported use of alcohol, tobacco, and cannabis; the degree of attribution of stimulant, depressant, and neutral effects to these drugs; and desirability ratings of stimulant and depressant effects ascribed to various drugs. Major findings were as follows: (a) On the RAS, reducing correlated positively with both sensation-seeking measures. (b) Seven of the nine personality-versus-drug-use correlations were positive and significant. (c) Generally, the effects attributed to drugs did not differ by sex, personality, or use. (d) However, frequent drinkers attributed stimulant effects to alcohol more strongly than depressant effects, whereas infrequent drinkers did the opposite. (e) The mean desirability ratings of stimulant and depressant drug effects correlated positively. (f) High disinhibitors rated drug effects of both kinds more favorably than did lows. (g) A similar, more favorable evaluation by high than by low general sensation seekers was significant for male subjects only. (h) Score on the Reducer-Augmenter Scale was not significantly predictive of subjects' desirability ratings.     

Effect of treatment with stimulant medication on nonverbal executive function and visuomotor speed in children with attention deficit/hyperactivity disorder (ADHD).

This study used a novel hidden maze learning test to examine the nature and magnitude of impairment on separable aspects of executive function in 36 children with ADHD. A within-subject analysis of children with ADHD was also conducted to assess cognitive effects of open-label stimulant treatment. Compared to 31 age-matched controls, unmedicated children with ADHD were slower and made significantly more errors that were indicative of relative impairment in prepotent response inhibition and ability to "maintain set" while using simple rules to complete the task. Open-label administration of stimulant medication led to faster and more efficient performance, with children with ADHD making fewer perseverative and rule-break errors than when off medication. This instrument might be useful in monitoring treatment response in specific aspects of executive function and in assisting with dose-titration decisions.     

Assessment of cognitive domains during treatment with OROS methylphenidate in adolescents with ADHD

Aim: To psychometrically assess cognitive domains in adolescents with ADHD during long-term open treatment with robust dosing of extended-release methylphenidate (OROS MPH).

Methods: Data were derived from a prospective clinical study of adolescent ADHD, employing the Cambridge Neuropsychological Test Automated Battery (CANTAB), before and after up to one year of treatment with OROS MPH. In the absence of placebo control, a similar age and gender group of youth without ADHD served as comparators.

Results: During the course of treatment with OROS MPH, ADHD youth’s performance significantly improved across multiple CANTAB tasks, including spatial working memory, rapid visual processing, verbal recognition memory, set shifting, and inhibition/vigilance. ADHD subjects’ scores in several CANTAB tasks, including spatial working memory, planning, and set shifting, were significantly more impaired at baseline compared to the non-ADHD comparison group; these significant differences were no longer seen at endpoint.

Conclusions: Statistically significant improvements in multiple cognitive domains were observed in a sample of adolescents with ADHD over the course of 12 months of robust treatment with extended-release methylphenidate. Rigorous, monitored stimulant treatment may be associated with objectively determined cognitive benefits; however, practice effects in this open trial cannot be ruled out. Further study on this important topic is warranted.     

The Use of Stimulant Medication and Behavioral Interventions for the Treatment of Attention Deficit Hyperactivity Disorder: A Survey of Parents’ Knowledge, Attitudes, and Experiences

We examined parents’ knowledge, attitudes, and information sources regarding Attention-Deficit/Hyperactivity Disorder (ADHD), including treatment with stimulant medication and behavioral interventions. Responses from parents with a child diagnosed with ADHD and parents without a child diagnosed with ADHD were also compared. Participants consisted of 146 parents of elementary age children from Wisconsin. The surveyed parents were aware of issues surrounding ADHD and the use of stimulant medication, but there were several areas where they possessed inaccurate or incomplete factual information. Parents who had a child diagnosed with ADHD rated the effects of stimulant medication more positively and side effects as less severe than other parents. They also rated behavioral interventions as less effective on all questions. Implications of the study are discussed.     

Acute Stimulant Treatment and Reinforcement Increase the Speed of Information Accumulation in Children with ADHD

The current studies utilized drift diffusion modeling (DDM) to examine how reinforcement and stimulant medication affect cognitive task performance in children with ADHD. In Study 1, children with (n = 25; 88 % male) and without ADHD (n = 33; 82 % male) completed a 2-choice discrimination task at baseline (100 trials) and again a week later under alternating reinforcement and no-reinforcement contingencies (400 trials total). In Study 2, participants with ADHD (n = 29; 72 % male) completed a double-blind, placebo-controlled trial of 0.3 and 0.6 mg/kg methylphenidate and completed the same task utilized in Study 1 at baseline (100 trials). Children with ADHD accumulated information at a much slower rate than controls, as evidenced by a lower drift rate. Groups were similar in nondecision time and boundary separation. Both reinforcement and stimulant medication markedly improved drift rate in children with ADHD (ds = 0.70 and 0.95 for reinforcement and methylphenidate, respectively); both treatments also reduced boundary separation (ds = 0.70 and 0.39). Reinforcement, which emphasized speeded accuracy, reduced nondecision time (d = 0.37), whereas stimulant medication increased nondecision time (d = 0.38). These studies provide initial evidence that frontline treatments for ADHD primarily impact cognitive performance in youth with ADHD by improving the speed/efficiency of information accumulation. Treatment effects on other DDM parameters may vary between treatments or interact with task parameters (number of trials, task difficulty). DDM, in conjunction with other approaches, may be helpful in clarifying the specific cognitive processes that are disrupted in ADHD, as well as the basic mechanisms that underlie the efficacy of ADHD treatments.     

The Efficacy, Safety, and Practicality of Treatments for Adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD)

Studies examining interventions for adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD) were reviewed to evaluate their efficacy. These efficacy findings were supplemented with a preliminary system for judging safety and practicality. Results suggest that the stimulant drug methylphenidate (MPH) is safe and well-established empirically, but has some problems with inconvenience and noncompliance. Preliminary research supports the efficacy, safety, and practicality of some psychotherapeutic interventions, including behavioral classroom interventions, note-taking training, and family therapy. Treatment with tricyclic antidepressants was judged to have minimal empirical support and debatable safety. Very little is known about long-term effectiveness of treatments, long-term compliance, or multimodal treatments for adolescents such as stimulants plus behavior therapy.