Effects of Stimulants on the Continuous Performance Test (CPT): Implications for CPT Use and Interpretation
Publication: The Journal of Neuropsychiatry and Clinical Neurosciences
Abstract
An increasing number of treatment plans for individuals with attention-deficit/hyperactivity disorder (ADHD), as well as other disorders, include stimulant medication. The purpose of this study was to investigate the effects of stimulant medications on attention and impulsivity as measured by continuous performance tests (CPTs). The effect of other stimulants (e.g., caffeine, nicotine) on CPT performance was examined as well. Although various versions of the CPT were used in the studies reviewed, the research supports improvements in CPT performance with stimulant treatment. Implications for the use of CPTs in evaluating the effects of medications on attention are discussed. Also presented are implications for control of common substances like nicotine or caffeine when CPT is used and interpreted as a measure of attention.
In the past 10 to 20 years, there has been an increase in the use of pharmacological treatment, and particularly the use of stimulants, for a variety of disorders. This increase is at least in part due to the effectiveness of stimulant medications for individuals with attention-deficit/hyperactivity disorder (ADHD), as well as other disorders across the lifespan.1 Among school-age children, this increase in the use of stimulant medication has been documented by a number of researchers.2–5 As a result of the increased use of stimulant medication, the American Academy of Child and Adolescent Psychiatry6 advocated systematic monitoring of medication effects across behavioral domains for children and youth with ADHD. The same need for medication monitoring extends into adulthood if optimal functioning is the desired outcome.
Inattention or distractibility is a behavior that is often targeted for change with medication. Swanson7 identified six measures that were found to be appropriate for monitoring pharmacological effects in children. Swanson included objective laboratory measures of inattention as one type of information that can be used to monitor medication effects. The continuous performance test (CPT) is one group of paradigms for the evaluation of attention (and, to a lesser degree, impulsivity) that has been used for medication monitoring. The CPT is reported to be the most popular clinic-based measure of sustained attention and vigilance,8 and it has been described as the most sensitive measure for monitoring medication effects.9,10 The basic paradigm of a CPT involves selective attention or vigilance for an infrequently occurring stimulus.11 CPTs are generally characterized by rapid presentation of continuously changing stimuli among which there is a designated “target” stimulus or “target” pattern. The duration of the task varies, but the task is intended to be of sufficient length to measure sustained attention.
The usefulness of a CPT in monitoring medication effects,12–14 as well as the effects of other treatments,15 has been researched. Some advantages and disadvantages of using a CPT to monitor the effects of medication are described by Bergman et al.16 One advantage to using a CPT is that CPTs are purported to have excellent face validity and appear to measure the ability of a person to concentrate on a single task for a certain length of time. Another advantage is that a CPT is an objective tool to gather quantifiable information on the improvement or deterioration of attention as a result of a particular treatment, in this case medication. CPTs also are inexpensive and easy to administer. Taken together, these advantages may explain the frequency with which a CPT is used as an objective measure of attention.16
The original CPT was developed in 1956 by Rosvold et al.17 to study vigilance. In the original CPT task, letters were presented visually one at a time, at a fixed rate, with 920 ms between presentations. The subject's task was to respond by pressing a lever whenever the letter X, designated as the target, appeared and to inhibit a response when any other letter appeared; this version can be referred to as the X-CPT. Rosvold et al. also introduced a variation of this task, the AX-CPT, in which the target was the letter X, but only if the X was immediately preceded by the letter A. Rosvold and colleagues found that the X-CPT correctly classified 84.2% to 89.5% of younger subjects with identified brain damage. Although the X-CPT had adequate classification accuracy, the classification accuracy improved with the more difficult AX-CPT.
Currently there are multiple variations in the components of the basic CPT task. For example, the target stimulus in the CPT may be a letter as in the original version, a number,18 a designated playing card,19 a picture of an object or person,20 or a word.21 The task may be the simpler X-CPT, or an AX-CPT, or a further modification of the AX such that the target must be preceded by itself (XX-CPT).22,23 Other versions may define the target such that color and letter are critical features (e.g., orange T followed by blue S,24 or such that two digits in a number series (or letters in an alphabetic string) are the same in two consecutive stimuli sets (Identical Pairs or CPT:IP25,26 ). Another modification involves a change in the response set such that the directions are to respond to all stimuli except the designated target (not-X-CPT) as in the Conners' CPT.27 In general, the CPTs that use pictures of objects have been used more frequently with younger children or individuals of limited cognitive ability,28 while the more difficult tasks involving repeated patterns, such as the CPT:IP, have been used predominantly with adults. In addition to changes in the target, presentation of the target differs; it may be visual, as in the original version of the CPT, it may be auditory,21 or it may use both auditory and visual stimuli within the same task.29
The target type and criteria are not the only variations among CPTs. Studies have varied the frequency of the target,30 the duration of the stimulus presentation,31 and the quality of the stimulus presented.32,33 Further modifications include the addition of “distraction conditions.”34,35 The time lapse between presentations of the stimuli (interstimulus interval; ISI) has been varied as well, some studies having used a shorter, longer, or variable interval.36,37 In addition, the CPT can be designed so that subjects receive feedback on their performance following either correct responses, incorrect responses, or both.38,39
Variables of interest in scoring the CPT have changed as well. When Rosvold and colleagues17 first introduced the CPT, the focus was on the number of correct hits as an indicator or index of attention. Since that time other variables have been used as measures of attention, including omission errors (the number of targets not responded to) and relative accuracy (the number of correct hits out of the total targets presented). In contrast, the number of commission errors (the number of responses to stimuli other than the target) is frequently reported as a measure of impulsivity. Sometimes, the reaction time (time elapsed between stimulus presentation and response) is reported along with the standard deviation of the reaction time. Alternatively, many researchers use the measures of sensitivity (d′) and bias (beta) based on signal detection theory in reporting CPT scores.26,40 The signal detection indices may be more sensitive to differences in CPT performance than either omission or commission errors.41 Sensitivity is dependent on the intensity of the stimulus and the sensitivity of the subject; it is believed to reflect the ability of the individual to discriminate between the signal (or target stimulus) and irrelevant noise (or nontarget stimuli). Bias or response style is presumed to be related to the strategy used in making decisions on whether to respond or not. Bias is believed to reflect the extent to which the individual is likely to respond quickly (and hence increase the likelihood of errors) or to respond more conservatively. However, concerns have been raised by some as to the applicability of signal detection theory to CPT performance.42,43
Since 1956, the CPT has continued to be used in the study of attention, as well as impulsivity, with consistent findings of sensitivity to dysfunction in the central nervous system.44 With this sensitivity to dysfunction, and an understanding that stimulant medications act on the central nervous system via interactions with neurotransmitters or neuromodulators, it is logical to assume that CPTs would be sensitive to stimulant-related changes in brain function as they relate to attention. It is generally believed that the catecholamine neurotransmitters (e.g., dopamine, norepinephrine) are involved in both attention and inhibition.45,46 The involvement of the dopaminergic system in children, adolescents, and adults with ADHD has been reviewed extensively,47 and this system has been implicated in brain–behavior models of attention.48–50
The extant meta-analyses have looked at research on specific effects of a single class of medication or of a single medication,51,52 with the type or version of CPT used kept constant. The purpose of the present review was to provide a synthesis of the CPT research related to both prescribed stimulant medications and other stimulants, in order to determine the effects of stimulants in general on attention as measured by the CPT. A secondary goal was to determine the extent to which the type of stimulant used should be considered in interpretation of CPT results.
The sheer number of CPT versions is a major disadvantage when trying to synthesize the literature quantitatively (e.g., through meta-analysis). There is no research to date on the relative sensitivity of the various CPTs or score types. When possible, we computed effect sizes (ES) and examined ES for differing CPT types and score types. Score types examined included correct hits, omission errors, commission errors, reaction time, sensitivity (d′), and bias (lnB or beta), these being the types more frequently reported. In addition, some studies reported on the mean ISI (i.e., the adaptive rate) or standard deviation of the reaction time, as well as various other indices of variability. Because of the variations in how results were reported, as well as the differing parameters of the tasks, the synthesis provided will be more qualitative than quantitative in nature.
METHODS
The literature search included review of citations listed in PsycINFO (310 entries), MEDLINE (192 entries), and ERIC (13 entries) from 1966 through 1999, using “continuous performance test” as a search prompt. When overlapping entries were accounted for, the total number of original entries was 342. Several studies cited in the databases, however, were not available in English or were specific to animals and therefore were not included in this review. Dissertations were included; in the event a dissertation had been published, the publication (as opposed to the dissertation) was included. Additional references were generated from the review of the cited articles. In some cases, although the research reviewed included a vigilance task, it was determined that the task used was not a “continuous performance test.” Because of the vast numbers of vigilance tasks in general as well as the variety of CPTs available, only those studies that included a vigilance task that constituted a CPT were included. For this review, the defining characteristics of a CPT were based on paradigms from Rosvold et al.17 such that the task had to involve the presentation of constantly changing stimuli with some clearly defined “target” stimulus or pattern that occurred at a low frequency relative to the number of stimuli presented over the duration of the task. Paper-and-pencil vigilance tasks, even when referred to as a continuous performance test,53 were not included. Of the identified articles, 77 were found to be empirical studies that included stimulant medications or other stimulants. These were then further limited to those studies that used a randomized, placebo-controlled design. As a result, only 45 studies were included in the final analysis.
Effect size (ES) was calculated when sufficient information was provided in an article reporting on an empirical study. ES values were computed to transform data to a common metric. When means and standard deviations were reported in a study, ES was calculated by dividing the difference between baseline scores (or placebo scores, if no baseline data were available) and medication scores by the standard deviation of the gain.54 As neither pre/post correlations nor test-retest reliabilities were consistently available for the various CPTs used, the calculated ES values should be considered conservative estimates. When means and standard deviations were not available, the ES values were derived from inferential statistics (e.g., F-values), using the procedure set by Wolf.55
RESULTS
Psychostimulants for ADHD
Psychostimulants or stimulant medications are the most frequently prescribed medications to address the behavioral complex of inattention, impulsivity, and hyperactivity associated with attention-deficit/hyperactivity disorder (ADHD) or attention deficit disorder (ADD). Psychostimulants are believed to act on the catecholaminergic system as they mimic the actions of dopamine and norepinephrine,56 both of which are believed to be involved in attention processes.49 The exact mechanisms by which psychostimulants bring about the changes in the catecholamines have not been determined as yet. It appears that dextroamphetamine, for example, increases the availability of norepinephrine, dopamine, or both, while it is believed that methylphenidate (MPH; Ritalin) has predominant effects on the dopaminergic system.56 Prescribed psychostimulants generally include methylphenidate, pemoline (Cylert), dextroamphetamine (d-amphetamine; Dexedrine), methamphetamine (Desoxyn), and a combination of amphetamine and dextroamphetamine (Adderall).
Stimulants have been found to be effective medications for children with ADHD for more than 20 years.57 Prescriptions for psychostimulants are becoming increasingly common; it is estimated that prescriptions increased by approximately 248% in the 1980s.58 Safer and Krager3,4 suggested, on the basis of their findings, that the number of children with ADHD who were treated with medication doubled every 4 to 7 years. Given that only 3% to 5% of the population is projected to have ADHD,59 this increase in the prescription rate of psychostimulants, and methylphenidate in particular, has raised concerns.60,61 Short-term improvements of attention and impulsivity with psychostimulants, shown on a variety of behavioral indices, are well established in the literature.62 Kavale51 performed a meta-analysis on 135 studies to examine the efficacy of stimulant drug treatment for ADHD on 5,300 children. To be included in his meta-analysis, a published study had to include a comparison group or condition (e.g., a placebo control). His study included MPH, dextroamphetamine, and pemoline. The conclusion Kavale reached was that treatment for hyperactivity with all major stimulant drugs, except caffeine, is effective. Attention and concentration, including speed, reaction time, and automatic functioning on simple tasks, were found to improve with stimulant medication, whereas the number of errors decreased with stimulant treatment. Moderate effect sizes were found on various measures of attention in Kavale's meta-analysis. For example, Porteus Mazes63 were used in 16 studies with a mean ES of 0.54. For the continuous performance or vigilance tasks across 8 studies, the mean ES was 0.56.17 In fact, the results suggested an average 75% decrease in error scores and a 65% decline in reaction times on CPTs. These findings are comparable with other studies.9,64–67
Of the 77 studies that addressed the effects of stimulant medications on CPT performance, 39 focused on methylphenidate. A summary of these findings by specific stimulant, as well as studies comparing the efficacy of stimulants and other medications, are presented below.
Methylphenidate
Methylphenidate is the most commonly used of the stimulant medications for the treatment of ADHD68–70 and has been found to result in improved behavior for 80% to 85% of the ADHD population.69 MPH has a short half-life (4 to 6 hours); therefore, it is commonly administered twice a day, once in the morning and once in the afternoon. A rebound effect may occur in the late afternoon or early evening, when the medication wears off in about one-third of the children with ADHD.56 With this rebound effect, symptoms of ADHD become evident again as the child becomes more irritable and noncompliant. This could explain why teachers notice more improvements with the use of the drug and parents notice more of the side effects. Because of the short half-life and potential rebound effect, increasing the number of times medication is consumed from two to three times per day is being considered by some practitioners.71 For these same reasons (short half-life and potential rebound effect), there has been interest in developing stimulants that remain effective for longer periods of time. Slow-Release Ritalin (SR-20) is one such medication and is increasingly being prescribed.57 For standard MPH, 0.3 mg/kg is the dose frequently prescribed; this dosage level has been found to be effective on both cognitive and behavior ratings, including CPT performance.62 Notably, attention, as measured by CPT performance, has been reported to improve with MPH not only in individuals with ADHD, but in control subjects as well.
Research suggests that MPH improves attention, impulse control, and possibly academic performance.72 For example, a meta-analysis by Losier et al.52 of studies using similar types of CPT tasks found that children with ADHD who were treated with MPH made significantly fewer commission and omission errors. Consistent with these findings, the majority of studies having randomized, placebo-controlled conditions that were included in this review indicated a reduction in both commission and omission errors with administration of MPH.13,73–87 Some studies indicated that MPH resulted only in significantly decreased commission errors. For example, one study using adult volunteers found reduced commission error scores but no reduction in omission errors or reaction time improvements.88 In other studies, involving children with ADHD, a main effect for MPH treatment was found only for omission errors. For example, using a visual X-CPT, Aman et al.89 found significant improvements in omission error scores. Improvement in omission errors or correct responses on an AX-CPT was found for aggressive and nonaggressive children90 and for children with ADD91 as well. Other researchers have found improved reaction time23,84,91,92: when reaction time was included as a measure of CPT performance and doses of MPH ranged from 0.3mg/kg to 0.9mg/kg, effect sizes ranged from 0.02 to 1.21.
Although a majority of studies focus on correct responses, omission errors, commission errors, and reaction time, a handful of studies have evaluated the effects of MPH on CPT performance by using signal detection theory indices of sensitivity (d′) and bias (lnB). For the five studies that included indices of SDT, as well as correct hits, omission errors, or commission errors, d′ was fairly consistent with the direct performance measures. For example, effect sizes for the Klorman et al.40 study were 0.41 for omission errors, 0.30 for commission errors, and 0.39 for d′. Interestingly, for the same study, dosage, and task parameters, the effects size of reaction (0.73) is not comparable, suggesting a greater impact on reaction time as opposed to other indices of performance and further suggesting that reaction time differences are not captured by d′. In a study by Solanto et al.,83 the effect size for correct hits (0.64) and d′ (0.55) were also fairly consistent. As with correct hits, omission errors, and commission errors, studies reporting on CPT performance as reflected by d′ and lnB generally suggest improved performance with stimulant medications.
Not all studies with MPH showed benefits. A few studies found no significant drug effects for MPH on commission errors, omission errors, correct responses, or reaction time.93 Handen et al.94 found reduced errors scores with MPH, but the improvements in performance were not statistically significant. Aman et al.95 found a ceiling effect on omission errors for the X-CPT used, and this resulted in no change being evident. Many studies that used the Gordon Diagnostic System (GDS)18 found significant drug effects when doses of approximately 0.3 mg/kg to 0.5 mg/kg were administered.96 Thus, the medication level, as opposed to the task, may account for the lack of positive results. Consistent with the idea that “effectiveness” of the treatment is in fact being measured, Kupietz and Balka,97 using the Test of Variables of Attention,98 found significant improvements in performance for both the placebo and the MPH conditions, suggesting that some documented improvements may be due to the individual's belief that medication will improve attention.
The majority of research to date on MPH has focused on school-age children or youth. As yet, less is known about the impact of MPH on preschoolers. Musten et al.79 used the GDS with preschoolers to investigate the usefulness of MPH (0.3mg/kg and 0.5mg/kg) with a preschool population as well. Results indicated omission scores on the GDS improved with MPH at both dosage levels (ES=0.26 and 0.33, respectively). It was concluded that MPH had the same effects with preschool and school aged children. With the focus on children and youth, there is a paucity of research with adults. Koelega99 suggested that the lack of published material on the effects of MPH on CPT performance in adults may be due to a ceiling effect associated with some of the CPT measures used. Aman et al.'s95 study of 12 normal adults with a mean age of 28.3 years found a decrease in commission errors with MPH, but no changes in reaction time or correct hits, possibly due to the ease of the task (i.e., a ceiling effect). Although available research on adults continues to be limited, preliminary findings are consistent with the majority of studies with children and youth, suggesting that MPH results in improved CPT performance.
Other Prescribed Psychostimulants
Although the majority of studies included MPH, it is not the only psychostimulant used in the treatment of attention problems. Others include dextroamphetamine (d-amphetamine; Dexedrine, slow-release Dexedrine spansule [DS]), and pemoline. Of these, dextroamphetamine is the second most frequently prescribed medication behind MPH for ADHD.62 Seven studies were found that examined the effects of the dextroamphetamines on CPT performance; however, no study using the CPT was found with the most recently developed dextroamphetamine saccharate/sulfate (Adderall).
The results for efficacy of dextroamphetamine as measured by the CPT are not consistent. Differences in age, clinical status, dosage levels, and CPT types may have resulted in the extreme differences in effect sizes found. Most studies using dextroamphetamine explored the effects on children with hyperactivity, ADHD, and ADD and on normal control subjects. Sostek et al.100 and Wiengartner et al.13 found improvements in vigilance for both control subjects and children with hyperactivity. Conners74 found improvements on both commission and omission errors with Dexedrine treatment. The research of Pelham et al.57 using the slow-release form of dextroamphetamine (DS) indicated beneficial effects of DS on CPT performance for the X-CPT, but not the AX-CPT.
Pemoline is another of the psychostimulant drugs; only two studies were found that examined the impact of pemoline on attention, as measured by the CPT. This drug, like most stimulants, has been found to improve motor activity, fine motor coordination, and goal-directed behavior and to reduce impulsiveness and distractibility.101 Pemoline has a longer half-life than dextroamphetamine or MPH, which allows for only one dose to be administered per day.57 Pemoline has been shown to have similar effects to MPH and SR-20 with children with ADHD at 56.25mg/day.57 On the other hand, Conners and Taylor93 found no significant effects on any CPT variable after administration of approximately 10 to 60 mg/day of pemoline. Thus, research related to the impact of pemoline on attention as measured by CPT performance is equivocal.
Other Stimulants
Additional substances included in the category of stimulants are caffeine and nicotine. Stimulants such as caffeine and nicotine are used daily in our society because they are thought to reduce fatigue and enhance concentration. There are mixed reports on caffeine as an effective stimulant. It is commonly believed that caffeine may decrease restlessness and fidgetiness, and increase sustained attention. Results with the CPT do not support these beliefs. One interesting finding was that when the effects of a number of stimulants were compared, only the difference between caffeine and methylphenidate was statistically significant, with minimal effect (ES=0.11) on CPT performance evidenced as a result of caffeine consumption.51 Similarly, minimal to no effects were found for commission or omission errors or reaction time after caffeine consumption for normal control groups.102 These results suggest that the impact of stimulants may depend not only on the CPT type, CPT index of performance used, stimulant type, and dosage, but also on the type of sample (clinical or control) included in the study.
The effects of nicotine exposure have been examined with the CPT as well. People who were exposed to nicotine in utero had higher rates of commission errors than the control group.103 More direct evidence of the impact of nicotine is available from empirically controlled studies. In adult smokers, normal intake of nicotine decreased the variability of reaction time but was not statistically significant.104 Using an adaptive-rate interstimulus interval (i.e., a condition in which the rate of presentation increased following a correct response), Levin et al.104 found that for subjects who did not usually smoke and were exposed to nicotine only as part of the research protocol, mean ISIs were significantly reduced compared with results prior to exposure. Levin's group105 found that low levels of nicotine (e.g., a 7-mg patch) resulted in decreased omission and commission errors for the control group. With a group of individuals with schizophrenia who were taking haloperidol (Haldol), Levin and colleagues106 investigated the interaction of various doses of nicotine and haloperidol. At the lowest nicotine level of 7 mg, decreased omission errors and faster reaction times were found, but commission errors increased. In contrast, at the highest dosage (21-mg patch), there was a strong, positive effect on commission errors (ES=0.77), a minimal effect on omission errors (ES=0.15), and a marked decrease in reaction time (ES=–0.58). Based on these limited studies, it would appear that nicotine exposure in utero may result in increased commission errors, while direct nicotine exposure may result in decreased omission errors, commission errors, and reaction time.
Comparative Results Across Stimulants
A number of studies have compared the efficacy of the various stimulant medications on attention, as well as impulsivity, as measured by CPT performance. Based on Kavale's51 meta-analysis, the mean effect sizes for MPH, dextroamphetamine, pemoline, and amphetamine (Benzedrine) were all moderate, ranging from 0.44 to 0.63. When standard MPH and SR-20 were compared, results suggested that both drugs were effective and that there were no significant differences in CPT performance between medication treatments.16,23,57 While SR-20 may be less effective in the afternoon than a second administration of MPH,16 results favored long-lasting stimulants for improvements in overall CPT performance.57 Conners74 compared the effects of MPH and dextroamphetamine treatment with children with minimal brain dysfunction and found that both drugs reduced the number of commission and omission errors as compared with the placebo condition. MPH was found to have slightly more positive effects than dextroamphetamine. Hagerman et al.14 compared MPH, dextroamphetamine, and placebo effects. Of the three conditions, only the MPH condition showed evidence of improved attention. Further, it was noted that MPH resulted in fewer reported side effects than dextroamphetamine.
Summary
Of the psychostimulants, MPH is the most studied. Of the MPH studies, the majority indicated improvement on some aspect of CPT performance; only five studies indicated no significant improvement. Results of studies using CPTs and psychostimulants are generally positive and suggest that, depending on the drug, the dosage, and the type of CPT used, improvement may be seen in attention, as evidenced by increased correct hits or decreased omission or commission errors. In a majority of studies, reaction time is decreased and less variable with stimulant medication. Additionally, stimulant medications generally resulted in decreased reaction times as well as decreased variability. Notably, research suggests that higher doses of stimulant medication are associated with improved performance only up to an optimal dosage, and then performance begins to decline.107 That these changes in CPT performance reflect differences in CNS functioning is evident in associated changes in event-related potential, such that MPH resulted in increased amplitude of P3 as well as decreased latency of P3 to target stimuli.23,77
DISCUSSION
Stimulant medications are frequently prescribed to address the behavioral symptoms associated with ADHD based on the belief that there is a neurological or neurochemical basis to attention problems. Psychostimulants have been found to improve CPT performance for both control subjects and clinical populations over the short term. Further research is needed on the effectiveness of the dextroamphetamines, particularly Adderall, as well as pemoline. Initial findings suggest that stimulants such as caffeine and nicotine do not affect overall CPT performance; however, because of the limited number of studies available and equivocal findings, it may be appropriate to control for (or consider) possible nicotine or caffeine effects when interpreting CPT results. It may be prudent for caffeine and nicotine intake be to controlled for as part of the standardization process for CPTs as well.
Additional research is needed with regard to the best CPT task parameters (score type, difficulty level, interstimulus interval) for appropriate evaluation of the effects of stimulant medications on attention. In some instances, significant pre/post-treatment differences were evident on one version of the CPT, but not others. Klorman et al.40 found the XX-CPT to be more sensitive to changes in brain functioning that resulted from medication for a clinical sample of children. When auditory and visual AX-CPT were compared, the auditory CPT was found to be more sensitive to apparent improvement.84 Other studies with an auditory version found improvements with stimulant medication or with placebo.98 Further, significant dose-by-task interactions were evident in studies that used more than one type of CPT. Thus, interpretation of CPT performance may be a function not only of the medication, but of variations in the task that increase or decrease the sensitivity of the CPT to the changes in the CNS.
Score type appears to make a difference as well; omission errors appear to be more sensitive than commission errors to medication, but not appreciably so. Although reported less frequently, correct hits and reaction time appear to be sensitive to changes in brain function as a result of medication as well. Signal detection theory indices (d′, beta) were not reported with sufficient frequency to determine their relative sensitivity to changes produced by stimulants. Similarly, we were not often able to compute effect sizes for other indices of CPT performance or for variability of reaction time and performance over time, and therefore we cannot comment on the relative sensitivity of these indices. Notably, regardless of the type of score used, there is consistent evidence that stimulants can have mixed effects; some score types show positive and moderate effect size while others, in the same study, demonstrate negative or minimal effect size.96,100,106 More research with various measures of CPT performance is needed to determine the most appropriate score type or index to be used in monitoring medication efficacy.
Presumably, medications are prescribed with the intent of improving one's functional ability. Negative impacts on attention can be detrimental to functioning and therefore need to be considered as an element of treatment monitoring. The American Academy of Child and Adolescent Psychiatry6 advocated the use of multiple methods for medication monitoring with children and youth (to include parent and teacher input) as well as adults with ADHD. Brown and Sawyer62 recommend that medication management be monitored over time as well. Although these concerns are specific to the monitoring of stimulant medication with children and youth, the same practice is needed with all medications for ADHD patients of all ages.
Direct observation of behavior in naturalistic settings would provide optimal monitoring information, but it is not always feasible. Reports of parents and teachers (or spouses, employers) can assist in monitoring; however, often there is a disparity of findings across raters, and obtaining this information over time can be intrusive in the workplace. As for laboratory measures, a vast number of neuropsychological measures can be used for the purpose of monitoring treatment effects on attention and executive control, so why use a CPT? The chief reasons are that a CPT provides a quick, relatively inexpensive, objective measure of the impact of medications on at least some components of attention, as well as their impact on processing speed (as measured by reaction time) and executive control.
Because there are some indications that stimulant medication may have a negative impact on some children,108 additional research is needed to identify the characteristics of those individuals who demonstrate a positive response to stimulants. Given dose effects on CPT performance and the need to identify the optimal dosage for a given individual, a CPT may provide an objective measure of dose effectiveness over time. However, monitoring stimulant effects by using objective measures over the short term, and simply addressing any immediate and measurable difficulties with inattention or disinhibition, is not sufficient. Currently there are few controlled long-term outcome studies on the effects of stimulant medications.1,109 Outcome studies of stimulant medication use that incorporate overall functioning across social, school or work, and community contexts over extensive periods of time are needed.
ACKNOWLEDGMENTS
This study was presented in part at the National Academy of Neuropsychology, Washington, DC, November 1998.
References
1.
Greenhill LL, Halperin JM, Abikoff H: Stimulant medications. J Am Acad Child Adolesc Psychiatry 1999; 38:503-512
2.
Gadow KD: Prevalence of drug therapy, in Practitioner's Guide to Psychoactive Drugs for Children and Adolescents, edited by Werry SJ, Aman MG. New York, Plenum, 1993, pp 57-74
3.
Safer DJ, Krager JM: A survey of medication treatment for hyperactive/inattention students. JAMA 1988; 260:2256-2258
4.
Safer DJ, Krager JM: Hyperactivity and inattentiveness: school assessment of stimulant treatment. Clin Pediatr 1989; 28:216-221
5.
Safer DJ, Zito JM, Pine EM: Increased methylphenidate usage for attention deficit disorder in the 1990s. Pediatrics 1996; 98:1084-1088
6.
American Academy of Child and Adolescent Psychiatry: Summary of the practice parameters for the assessment and treatment of children, adolescents and adults with ADHD. J Am Acad Child Adolesc Psychiatry 1997; 36:1311-1317
7.
Swanson JM: Measures of cognitive functioning appropriate for use in pediatric psychopharmacological research studies. Psychopharmacol Bull 1985; 21:887-895
8.
DuPaul GJ, Anastopoulos AD, Shelton TL, et al: Multimethod assessment of attention deficit hyperactivity disorder: the diagnostic utility of clinic-based tests. J Clin Child Psychol 1992; 21:394-402
9.
Aman MG: Drugs, learning, and the psychotherapies, in Pediatric Psychopharmacology: The Use of Behavior Modifying Drugs in Children, edited by Werry JS. New York, Brunner/ Mazel, 1978, pp 79-108
10.
Kornetsky C: The use of a simple test of attention as a measure of drug effects in schizophrenic patients. Psychopharmacologia 1972; 24:99-106
11.
Eliason MJ, Richman LC: The continuous performance test in learning disabled and nondisabled children. J Learn Disabil 1987; 20:614-619
12.
Aman MG, Kern RA, McGhee DE, et al: Fenfluramine and methylphenidate in children with mental retardation and attention deficit hyperactivity disorder: laboratory effects. J Autism Dev Disord 1993; 23:491-506
13.
Weingartner H, Rapoport JL, Buchsbaum MS, et al: Cognitive processes in normal and hyperactive children and their response to amphetamine treatment. J Abnorm Psychol 1980; 89:25-37
14.
Hagerman RJ, Murphy MA, Wittenberger MD: A controlled trial of stimulant medication in children with the fragile X syndrome. Am J Med Genet 1988; 30:377-392
15.
Benedict RHB, Harris AE, Markow T, et al: The effects of attention training on information processing in schizophrenia. Schizophr Bull 1994; 20:537-546
16.
Bergman A, Winters L, Cornblatt B: Methylphenidate: effects on sustained attention, in Ritalin: Theory and Management, edited by Greenhill LL, Osman BB. New York, Mary Ann Liebert, 1991, pp 223-232
17.
Rosvold H, Mirsky A, Sarason I, et al: A continuous performance test of brain damage. Journal of Consulting Psychology 1956; 20:343-350
18.
Gordon M: The Gordon Diagnostic System. DeWitt, NY, Gordon Systems, 1983
19.
Erlenmeyer-Kimling L, Cornblatt B: Attentional measures in a study of children at high risk for schizophrenia. J Psychiatr Res 1978; 14:93-98
20.
Anderson VE, Siegel FS, Fisch RO, et al: Response of phenylketonuric children on a continuous performance test. J Abnorm Psychol 1969; 74:358-362
21.
Earle-Boyer EA, Serper MR, Davidson M, et al: Continuous performance tests in schizophrenic patients: stimulus and medication effects on performance. Psychiatry Res 1991; 37:47-56
22.
Coons HW, Klorman R, Borgstedt AD: Effects of methylphenidate on adolescents with a childhood history of attention deficit disorder, II: information processing. J Am Acad Child Adolesc Psychiatry 1987; 26:368-374
23.
Fitzpatrick PA, Klorman R, Brumaghim JT, et al: Effects of sustained release and standard preparations of methylphenidate on attention deficit disorder. J Am Acad Child Adolesc Psychiatry 1992; 31:226-234
24.
Garfinkel BG, Klee SH: A computerized assessment battery for attention deficits. Psychiatry Hospitals 1983; 14:163-166
25.
Cornblatt BA, Lenzenweger MF, Erlenmeyer-Kimling L: The Continuous Performance Test, identical pairs version (CPT-IP), II: contrasting attentional profiles in schizophrenia and depressed patients. Psychiatry Res 1989; 29:65-85
26.
Keilp JG, Herrera J, Stritzke P, et al: The Continuous Performance Test, identical pairs version (CPT-IP), III: brain functioning during performance of numbers and shapes subtasks. Psychiatry Research: Neuroimaging 1997; 74:35-45
27.
Conners CK: Conners' Continuous Performance Test. Ottawa, MultiHealth Systems, 1995
28.
Harper GW, Ottinger DR: The performance of hyperactive and control preschoolers on a new computerized measure of visual vigilance: the Preschool Vigilance Task. J Child Psychol Psychiatry 1992; 33:1365-1372
29.
Sandford JA, Turner A: Manual for the Intermediate and Visual Auditory Continuous Performance Test. Richmond, VA, authors, 1995
30.
Beale IL, Matthew PJ, Oliver S, et al: Performance of disabled and normal readers on the Continuous Performance Test. J Abnorm Child Psychol 1987; 15:229-238
31.
Chee P, Logan G, Schachar R, et al: Effects of event rate and display time on sustained attention in hyperactive, normal, and control children. J Abnorm Child Psychol 1989; 17:371-391
32.
Buchsbaum MS, Nuechterlein KH, Haier RJ, et al: Glucose metabolic rate in normals and schizophrenics during the Continuous Performance Test assessed by positron emission tomography. Br J Psychiatry 1990; 156:216-227
33.
Ernst M, Liebenauer LL, Tebeka D, et al: Selegiline in ADHD adults: plasma monamines and monamine metabolites. Neuropsychopharmacology 1997; 16:276-284
34.
Hoy E, Weiss G, Minde K, et al: The hyperactive child at adolescence: cognitive, emotional, and social functioning. J Abnorm Child Psychol 1978; 6:311-324
35.
Rutschmann J, Cornblatt B, Erlenmeyer-Kimling L: Sustained attention in children at risk for schizophrenia: report on a continuous performance test. Arch Gen Psychiatry 1977; 34:571-575
36.
Girardi NL, Shaywitz SE, Marchione K, et al: Blunted catecholamine responses after glucose ingestion in children with attention deficit disorder. Pediatr Res 1995; 38:539-542
37.
Ruekert L, Grafman J: Sustained deficits in patients with frontal lesions. Neuropsychologia 1996; 34:953-963
38.
Nuechterlein KH: Signal detection in vigilance tasks and behavioral attributes of schizophrenic mothers and among hyperactive children. J Abnorm Psychol 1983; 92:4-28
39.
O'Dougherty M, Nuechterlein KH, Drew B: Hyperactive and hypoxic children: signal detection, sustained attention, and behavior. J Abnorm Psychol 1984; 93:178-191
40.
Klorman R, Brumaghim JT, Salzman LF, et al: Effects of methylphenidate on attention-deficit hyperactivity disorder with and without aggressive/noncompliant features. J Abnorm Psychol 1988; 97:413-422
41.
Lam CM, Beale IL: Relations among sustained attention, reading performance, and teachers' ratings of behavior problems. Remedial and Special Education (RASE) 1991; 12:40-47
42.
Jerison HJ: Signal detection theory in the analysis of human vigilance. Hum Factors 1967; 9:285-288
43.
Parasuraman R: Memory load and event rate control sensitivity decrements in sustained attention. Science 1979; 205:924-927
44.
Reynolds CR, Lowe PA, Moore JJ, et al: Sensitivity and specificity of CPT in diagnosis of ADHD: much of one and none of the other. Presented at the Annual Meeting of the National Academy of Neuropsychologists, Washington, DC, November 1998
45.
Clark CR, Geffen GM, Geffen LB: Catecholamines and attention, I: animal and clinical studies. Neurosci Biobehav Rev 1987; 11:341-352
46.
Clark CR, Geffen GM, Geffen LB: Catecholamines and attention, II: pharmacological studies in normal humans. Neurosci Biobehav Rev 1987; 11:341-352
47.
Zametkin AJ, Rapoport JL: Neurobiology of attention deficit disorder with hyperactivity: where have we come in 50 years? J Am Acad Child Adolesc Psychiatry 1987; 26:676-686
48.
Heilman KM, Voeller KKS, Nadeau SE: A possible pathophysiological substrate of attention deficit hyperactivity disorder. J Child Neurol 1991; 6 (suppl):S76-S81
49.
Levy F: The dopamine theory of attention deficit hyperactivity disorder (ADHD). Aust N Z J Psychiatry 1991; 25:277-283
50.
Posner MI, Inhoff AW, Fredrich FS: Isolating attentional systems: a cognitive-anatomical analysis. Psychobiology 1987; 15:107-121
51.
Kavale K: The efficacy of stimulant drug treatment for hyperactivity: a meta-analysis. J Learn Disabil 1982; 15:280-289
52.
Losier BJ, McGrath PJ, Klein RM: Error patterns of the continuous performance test in non-medicated and medicated samples of children with and without ADHD: a meta-analytic review. J Child Psychol Psychiatry 1996; 37:971-987
53.
Wildman RW, Wildman RW II: An investigation into the possibility of irreversible central nervous system damage as a result of long-term chlorpromazine medication. J Clin Psychol 1975; 31:340-344
54.
Glass GV: Integrating findings: the meta-analysis of research. Review of Research in Education 1977; 5:351-379
55.
Wolf FM: Meta-analysis: Quantitative Methods for Research Synthesis. Beverly Hills, CA, Sage, 1986
56.
Barkley RA, DuPaul GJ, Connor DF: Stimulants, in Practitioner's Guide to Psychoactive Drugs for Children and Adolescents, 2nd edition, edited by Werry JS, Aman MG. New York, Plenum, 1999, pp. 213-248
57.
Pelham WE, Greenslade KE, Voale-Hamilton M, et al: Relative efficacy of long-acting stimulant on children with attention deficit and hyperactivity disorder: a comparison of standard methylphenidate, sustained-release methylphenidate, sustained-release dextroamphetamine and pemoline. Pediatrics 1990; 86:226-237
58.
Kelly DP, Aylward GP: Attention deficits in school-aged children and adolescents: current issues and practice. Pediatr Clin North Am 1992; 39:487-512
59.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Washington, DC, American Psychiatric Association, 1994
60.
Barkley RA: Attention Deficit/Hyperactivity Disorder: A Handbook for Diagnosis and Treatment, 2nd edition. New York, Guilford, 1998
61.
Pelham WE: Pharmacotherapy for children with attention deficit hyperactivity disorder. School Psychology Review 1993; 22:199-227
62.
Brown RT, Sawyer MG: Medications for School-age Children. New York, Guilford, 1998
63.
Porteus SD: The Maze Test and Clinical Psychology. Palo Alto, CA, Pacific Books, 1959
64.
Barkley RA: A review of stimulant drug research with hyperactive children. J Child Psychol Psychiatry 1977; 18:137-155
65.
Klorman R, Brumaghim JT, Fitzpatrick PA, et al: Clinical effects of a controlled trial of methylphenidate on adolescents with attention deficit disorder. J Am Acad Child Adolesc Psychiatry 1990; 29:702-709
66.
Sandoval J: The measurement of hyperactive syndrome in children. Review of Educational Research 1977; 47:293-318
67.
Whalen CK, Henker B: Psychostimulants and children: a review and analysis. Psychol Bull 1976; 83:1113-1130
68.
Kwasman A, Tinsley BJ, Lepper HS: Pediatricians' knowledge and attitudes concerning diagnosis and treatment of attention deficit and hyperactivity disorders: a national survey approach. Arch Pediatr Adolesc Med 1995; 149:1211-1216
69.
Quay HC: Inhibition and attention deficit hyperactivity disorder. J Abnorm Child Psychol 1997; 25:7-13
70.
Winsberg BG, Kupietz SS, Yepes LE: Ineffectiveness of imipramine in children who fail to respond to methylphenidate. J Autism Dev Disord 1980; 10:129-137
71.
Schacher RJ, Tannock R, Cunningham C, et al: Behavioral, situational, and temporal effects of treatment of ADHD with methylphenidate. J Am Acad Child Adolesc Psychiatry 1997; 36:754-763
72.
Brown RT, Borden KA, Wynne ME, et al: Methylphenidate and cognitive therapy with ADD children: a methodological reconsideration. J Abnorm Child Psychol 1986; 14:481-497
73.
Barkley RA, Fischer RF, Newby RF, et al: Development of a multimethod clinical protocol for assessing stimulant drug response in children with attention deficit disorder. Journal of Clinical Child Psychology 1988; 17:14-24
74.
Conners CK: Psychological effects of stimulant drugs in children with minimal brain dysfunction. Pediatrics 1972; 49:702-708
75.
Handen BL, Breaux AM, Gosling A, et al: Efficacy of methylphenidate among mentally retarded children with attention deficit hyperactivity disorder. Pediatrics 1990; 86:922-930
76.
Klorman R, Salzman LF, Bauer LO, et al: Effects of two doses of methylphenidate on cross-situational and borderline hyperactive children's evoked potentials. Electroencephalogr Clin Neurophysiol 1983; 56:169-185
77.
Michael RL, Klorman R, Salzman LF, et al: Normalizing effects of methylphenidate on hyperactive children's vigilance performance and evoked potentials. Psychophysiology 1981; 18:665-677
78.
Milich R, Licht BG, Murphy DA, et al: Attention-deficit hyperactivity disordered boys' evaluations of and attributions for task performance on medication versus placebo. J Abnorm Psychol 1989; 98:280-284
79.
Musten LM, Firestone P, Pisterman S, et al: Effects of methylphenidate on preschool children with ADHD: cognitive and behavioral functions. J Am Acad Child Adolesc Psychiatry 1997; 36:1407-1415
80.
Peloquin LJ, Klorman R: Effects of methylphenidate and performance in memory scanning and vigilance. J Abnorm Psychol 1986; 95:88-98
81.
Rapport MD, Carlson GA, Kelly KL, et al: Methylphenidate and desipramine in hospitalized children, I: separate and combined effects on cognitive function. J Am Acad Child Adolesc Psychiatry 1993; 32:333-342
82.
Rapport MD, DuPaul GJ, Stoner G, et al: Comparing classroom and clinic measures of attention deficit disorder: differential, idiosyncratic, and dose-response effects of methylphenidate. J Consult Clin Psychol 1986; 54:334-341
83.
Solanto MV, Wender EH, Bartell SS: Effects of methylphenidate and behavioral contingencies on sustained attention in attention deficit hyperactivity disorder: a test of the reward dysfunction hypothesis. J Child Adolesc Psychopharmacol 1997; 7:123-136
84.
Sykes DH, Douglas VI, Morganstern GL: The effect of methylphenidate (Ritalin) on sustained attention in hyperactive children. Psychopharmacologia 1972; 25:262-274
85.
Sykes DH, Douglas VI, Weiss G, et al: Attention in hyperactive children and the effects of methylphenidate (Ritalin). J Child Psychol Psychiatry 1971; 12:129-139
86.
Verbaten MN, Overtoom CCE, Koelega HS, et al: Methylphenidate influences on both early and late ERP waves of ADHD children in a continuous performance test. J Abnorm Child Psychol 1994; 22:561-578
87.
Werry JS, Aman MG: Methylphenidate in hyperactive and enuretic children, in The Psychobiology of Childhood, edited by Greenhill LL, Shopsin B. Jamaica, NY, Spectrum, 1984, pp 183-195
88.
Aman MG, Werry JS, Paxton JW, et al: Effects of sodium valproate on psychomotor performance in children as a function of dose fluctuations in concentration and diagnosis. Epilepsia 1984; 28:115-124
89.
Aman MG, Marks RW, Turbott SH, et al: Methylphenidate and thioridazine in the treatment of intellectually subaverage children: effects on cognitive-motor performance. J Am Acad Child Adolesc Psychiatry 1991; 30:816-824
90.
Barkley RA, McMurray MB, Eldebrook CS, et al: The response of aggressive and non-aggressive attention deficit and hyperactivity disorder children to two doses of methylphenidate. J Am Acad Child Adolesc Psychiatry 1989; 28:873-881
91.
Klorman R, Brumaghim JT, Fitzpatrick PA, et al: Methylphenidate speeds evaluation processes of attention deficit disorder adolescents during a continuous performance test. J Abnorm Child Psychol 1991; 19:263-283
92.
Werry JS, Aman MG, Diamond E: Imipramine and methylphenidate in hyperactive children. J Child Psychol Psychiatry 1980; 21:27-35
93.
Conners CK, Taylor E: Pemoline, methylphenidate, and placebo in children with minimal brain dysfunction. Arch Gen Psychiatry 1980; 37:922-930
94.
Handen BL, Breaux AM, Janosky J, et al: Effects and noneffects of methylphenidate in children with mental retardation and ADHD. J Am Acad Child Adolesc Psychiatry 1992; 31:455-461
95.
Aman MG, Vamos W, Werry JS: Effects of methylphenidate in normal adults with reference to drug action in hyperactivity. Aust N Z J Psychiatry 1984; 18:86-88
96.
Brown RT, Sexson SB: A controlled trial of methylphenidate in black adolescents. Clin Pediatr 1988; 27:74-81
97.
Kupietz SS, Balka EB: Alterations in vigilance performance of children receiving amitriptyline and methylphenidate pharmacotherapy. Psychopharmacology 1976; 50:29-33
98.
Greenberg LM: The Test of Variables of Attention (TOVA). Los Alamitos, CA, Universal Attention Disorders, Inc, 1991
99.
Koelega HS: Stimulant drugs and vigilance performance: a review. Psychopharmacology 1993; 111:1-16
100.
Sostek AJ, Buchsbaum MS, Rapoport JL: Effects of amphetamine on vigilance performance in normal and hyperactive children. J Abnorm Child Psychol 1980; 8:491-500
101.
Konopasek DE: Medication “fact sheet,” 1998 edition. Anchorage, AK, Arctic Tern, 1997
102.
Bernstein GS, Carroll ME, Crosby RD, et al: Caffeine effects on learning, performance, and anxiety in normal school-aged children. J Am Acad Child Adolesc Psychiatry 1994; 33:407-415
103.
Fried PA, Watkinson B:12- and 24-month neurobehavioural follow-up of children prenatally exposed to marihuana, cigarettes and alcohol. Neurotoxicol Teratol 1988; 18:305-313
104.
Levin ED, Conners CK, Sparrow E, et al: Nicotine effects on adults with attention-deficit/hyperactivity disorder. Psychopharmacology 1996; 123:55-63
105.
Levin ED, Conners CK, Silva D, et al: Transdermal nicotine effects on attention. Psychopharmacology 1998; 123:55-63
106.
Levin ED, Wilson W, Rose JE, et al: Nicotine-haloperidol interactions and cognitive performance in schizophrenics. Neuropsychopharmacology 1996; 15:429-436
107.
Rapport MD, Jones JT, DuPaul GJ, et al: Attention deficit disorder and methylphenidate: group and single subject analyses of dose effects on attention in clinic and classroom settings. J Clin Child Psychol 1987; 16:329-338
108.
Biederman J, Faraone SV, Keenan K, et al: Familial association between attention deficit disorder and anxiety disorders. Am J Psychiatry 1991; 148:251-256
109.
Brown RT: Long term treatment with ADD children: a call for more research. Developmental and Behavioral Pediatrics 1986; 7:173-174
Information & Authors
Information
Published In
History
Published online: 1 August 2001
Published in print: August 2001
Authors
Metrics & Citations
Metrics
Citations
Export Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.
For more information or tips please see 'Downloading to a citation manager' in the Help menu.
View Options
View options
PDF/EPUB
View PDF/EPUBGet Access
Login options
Already a subscriber? Access your subscription through your login credentials or your institution for full access to this article.
Personal login Institutional Login Open Athens loginNot a subscriber?
PsychiatryOnline subscription options offer access to the DSM-5-TR® library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.
Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).