ADHD Articles
New Study Shows Prevalence of ADHD May Be Underestimated
Understanding and Treating Adult ADHD
Understanding and Treating Adult ADHD
Martin L. Korn MD Disclosures
Introduction
Attention-deficit/hyperactivity disorder (ADHD) is increasingly being recognized as a disorder of not only children but of adults as well. The adult forms of ADHD can be very disabling but often go unrecognized. At this year's US Psychiatric & Mental Health Congress, Michael A. Schwartz, MD,[1] from Case Western Reserve University, Cleveland, Ohio, focused on the basic mechanisms underlying the disorder and their relationship with current treatment options and interventions.
Recognizing Adult ADHD
Although child psychiatrists have appreciated the impact and prevalence of the disorder, it is only lately that adult psychiatrists are also beginning to recognize similar findings. Similar to the experience with children, adult males with ADHD are more easily identified then are adult females. Males in general tend to manifest more problems in areas such as hyperactivity or antisocial behavior. It is these disturbing behaviors that are more likely to come to clinical attention. Women can also suffer from the disorder, however, they tend to manifest predominantly attentional problems. As more cases are identified in children, parents are being evaluated more closely for evidence of genetic transmission.
Attention, like intelligence, is distributed along a bell-shaped curve. Although those at the more extreme lower end of the curve, by definition, manifest greater difficulties with attention, it has been difficult to identify specific disease states that correspond to these deficits in attention. ADHD represents, therefore, a multifactorial disorder with many differing etiologies and presentations. Cultural elements may come into play if society demands a high degree of concentration and focus from all of its members. In this kind of rigorous society, problems in attention will be seen as more problematic than in a less structured culture. Although the biological substratum is very significant, the fact that there are multiple factors make it clear that there is not just 1 overarching theory of ADHD.
Neurobiology
It has been estimated that there are approximately 100 billion neurons. This figure is 15 times the world's population. Of the 100 billion neurons, 20 billion are glutaminergic cells and 8 billion are GABAergic cells. The monoamines that are the primary target for most available psychotropic agents form a small minority of the neurons. There are only 50,000 norepinephrine-containing cells, 250,000 dopamine-containing, and 250,000 serotonin-containing cells. These monoamine cells, despite their very small absolute number, branch widely and connect with and serve to modulate many of the billions of other neurons. They are responsible for "fine-tuning" central nervous system processes, including attention. An analogy may be made to the lighting system in an auditorium. Serotonergic neurons are not responsible for the lighting system itself, but act as the "dimmer switch." They are able to turn the intensity of the lights up and down. Alternatively, the catecholamines, including norepinephrine and dopamine, serve to focus attention as a spotlight would on a stage. The nicotinic system also helps in the attentional process.
Genetic Factors
Adoption and twin studies confirm that genetics play a significant role in the evolution of ADHD. Monozygotic twins demonstrate a 2-fold greater risk of ADHD compared with that for dizygotic twins. The dopamine receptor has been implicated as a possible genetic factor. Several subtypes of the dopamine receptor have been identified and the dopamine-2 (D2) receptor has been implicated most frequently in schizophrenia. The D4 receptor is distributed in the frontal cortex as well as in the hippocampus and entorhinal cortex. There are 8 variants of the D4 receptor. The D4,4 variant is found in 66% of the population. The D4,7 receptor variant is more commonly found in individuals with high scores on tests of impulsiveness, excitability and novelty-seeking behavior. D4,7 is also found most often in patients with ADHD.
Clinical Presentations
Approximately 50% to 80% of ADHD cases will persist into adolescence and 30% to 50% will continue into adulthood. However, the clinical presentations change as one ages. In younger children, hyperactivity is much more common; in adolescents, oppositional and restless behavior becomes more predominant; in adulthood, the hyperactivity diminishes and problems with attention becomes more prominent.[2]
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV)[3] describes 3 major subtypes of ADHD: ADHD, predominantly inattentive type; ADHD, predominantly hyperactive-impulsive type; and ADHD combined type.[3] There appears to be cognitive processing differences between the primarily inattentive type of ADHD and the combined hyperactive/inattentive type. The inattentive type manifests slower information processing and problems with focused or selective attention. These individuals appear to be daydreaming, "spaced out" and easily confused. In patients with the combined type disorder, there are problems in sustaining attention, thus these individuals present as distractible.
One of the most common complaints of an individual with adult ADHD is the sense of demoralization and failure. This may be due to the inability to achieve life goals or, alternatively, may be secondary to the presence of comorbid depression. The experience of cognitive disorganization related to problems in working memory points to an inability to complete tasks effectively. The presence of impulsive behavior often leads to negative feedback and this also contributes to the overall sense of failure.
Some have criticized that ADHD is an artifactual diagnosis resulting from the criteria established in the DSM system of classification. However, this is clearly unfounded because many countries and cultures have been found to have equal or greater rates of ADHD, with estimates ranging from 3% to 5%. The variance in diagnostic criteria explains some of the differences in rates. The International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10) criteria, for example, emphasize hyperactivity and therefore estimates of prevalence rates in adults using these criteria may be lower than estimated rates based on DSM-IV.[4,5]
ADHD comorbidity:
|
Females |
Males |
|
|
bipolar disorder |
8% |
14% |
|
Depression |
35% |
25% |
|
Anxiety disorder |
50% |
50% |
|
substance abuse |
> 15% |
> 25% |
- All these rates were substantially greater than the rates in normal controls.
Comorbidity
There are very high rates of comorbidity among patients with ADHD. These comorbid conditions include personality disorders, substance abuse, mood and anxiety disorders, Tourette's syndrome, and obsessive-compulsive disorder among others. Biederman and colleagues,[6] found that the rate of bipolar disorder in patients with ADHD was about 8% in females and 14% in males. Depression was present in approximately 35% of females with ADHD and 25% of males. Anxiety disorders were found in about 50% of both males and females. Substance abuse was noted in over 15% of females and over 25% of males. All these rates were substantially greater than the rates in normal controls.
The overlap between ADHD and bipolar disorder remains controversial. Since symptoms such as inattention, distractibility, hyperactivity, and impulsiveness may be seen in both disorders, it may be difficult to distinguish between them. However, these are clearly 2 separate syndromes and not all cases of ADHD can be subsumed under the bipolar syndrome.[7] However, some studies have shown a higher rate of affective disorders in families of patients with ADHD.[8]
In the ICD-10, the presence of a comorbid affective syndrome is a basis for exclusion from the ADHD diagnosis. This is not true in the DSM-IV, which accounts for some of the prevalence differences between countries. In general, comorbid conditions should be treated first and the ADHD secondarily. Treatment with stimulants may precipitate a manic episode in an individual with bipolar disorder, so the clinician should exercise caution if manic depression is suspected.
Psychopharmacology
Stimulants are still the treatment of choice in ADHD. Originally used extensively for weight loss, they have developed a reputation for their addictive potential. Although habituation to the anorectic elements of the drug may be seen, this does not occur when these medications are used to treat ADHD. Since the rate of substance abuse is high in patients with ADHD,[9,10] there has been consistent concern about the abuse potential with stimulant medication. However, several studies have shown that stimulants may actually help with craving and substance abuse issues.[11,12] Biederman and colleagues[13] found that untreated ADHD is a significant risk factor for substance use disorder in adolescence, however, pharmacotherapy is associated with an 85% reduction in risk for substance use disorder in youths. The rate in medicated ADHD patients was actually equal to the rate in normal controls.
The prescription rates for methylphenidate have risen dramatically since 1991. This has only leveled off recently because of the introduction of Adderall (mixed salts of a single-entity amphetamine product), a mixed amphetamine/dextroamphetamine medication. Adderall is preferred by some patients for its therapeutic effects. When administered in higher doses, the therapeutic effect may be more prolonged. More recently, slow-release forms of methylphenidate have been developed.
Stimulants appear to work through the release of the catecholamines into the synaptic clefts. They also block the reuptake of catecholamines, inhibit monoamine oxidase (MAO) enzymes and act as false neurotransmitters. The effectiveness of these medications appears to be most closely related to the effect on norepinephrine rather than dopamine. Venlafaxine has been shown to be effective, and this medication blocks the reuptake of norepinephrine as well as serotonin.[14] At high doses, however, venlafaxine may also block dopamine reuptake as well.
There are several nonstimulant medications now available that have been shown to have utility in the treatment of ADHD. Buproprion has been shown to be effective in several studies, as have clonidine and guanfacine also have been shown to have utility in the disorder.[15] Atomoxetine, a norepinephrine reuptake inhibitor has been shown to be effective in adults.[16] There are 4 placebo controlled studies demonstrating effectiveness, one of which was in adults. Weight loss is a side effect in approximately 15% to 20%.[16] The nonstimulant medications may be advantageous in that they are not controlled substances. Although they take several weeks to work, they do not have the rapid onset/offset effect of stimulant medications.
Conclusion
ADHD is now widely recognized as a disorder that is found in both children and adults. Many negative consequences result from the untreated condition including antisocial behavior, poor vocational and social functioning, and difficulties with substance abuse. Despite these many difficulties, psychopharmacologic and therapeutic interventions may successfully improve the negative outlook. Greater clinician awareness of the nature of the disorder and the range of treatments available is clearly warranted to improve success rates for a neglected but treatable disorder.
References
Schwartz MA. Treatment of dementia with cholinesterase inhibitors: improving quality of life. Adult ADHD: advances in understanding and treatment. Program and abstracts of the US Psychiatric & Mental Health Congress 2001; November 15-18, 2001, Boston, Massachusetts. 22-3
Mannuzza S, Klein RG. Adolescent and adult outcomes in attention deficit/hyperactivity disorder. In: Quay HC, Hogan AE, eds. Handbook of Disruptive Behavior Disorders. New York, NY: Klumer Academic/Plenum Publishers; 1999:279-294.
Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition (DSM-IV). Washington, DC: American Psychiatric Association; 1994.
Foreman DM, Foreman D, Prendergast M, Minty B. Is clinic prevalence of ICD-10 hyperkinesis underestimated? Impact of increasing awareness by a questionnaire screen in an UK clinic. Eur Child Adolesc Psychiatry. 2001;10:130-134.
Tripp G, Luk SL, Schaughency EA, Singh R. DSM-IV and ICD-10: a comparison of the correlates of ADHD and hyperkinetic disorder. J Am Acad Child Adolesc Psychiatry. 1999;38:156-164.
Biederman J, Faraone SV, Spencer T, et al. Patterns of psychiatric comorbidity, cognition, and psychosocial functioning in adults with attention deficit hyperactivity disorder. Am J Psychiatry.1993;150:1792-1798.
Milberger S, Biederman J, Faraone SV, Murphy J, Tsuang MT. Attention deficit hyperactivity disorder and comorbid disorders: issues of overlapping symptoms. Am J Psychiatry. 1995;152:1793-1799.
Biederman J, Munir K, Knee D, et al. High rate of affective disorders in probands with attention deficit disorder and in their relatives: a controlled family study.Am J Psychiatry. 1987;144:330-333.
Biederman J, Wilens TE, Mick E, Faraone SV, Spencer T. Does attention-deficit hyperactivity disorder impact the developmental course of drug and alcohol abuse and dependence? Biol Psychiatry. 1998;44:269-273.
Wilens TE, Biederman J, Mick E, Faraone SV, Spencer T. Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders. J Nerv Ment Dis. 1997;185:475-482.
Levin FR, Evans SM, McDowell DM, Kleber HD. Methylphenidate treatment for cocaine abusers with adult attention-deficit/hyperactivity disorder: a pilot study. J Clin Psychiatry. 1998;59:300-305.
Grabowski J, Roache JD, Schmitz JM, Rhodes H, Creson D, Korszum A. Replacement medication for cocaine dependence: methylphenidate. J Clin Psychopharmacol. 1997;17:485-488.
Biederman J, Wilens T, Mick E, Spencer T, Faraone SV. Pharmacotherapy of attention-deficit/hyperactivity disorder reduces risk for substance use disorder. Pediatrics. 1999;104:e20.
Findling RL, Schwartz MA, Flannery DJ, Manos MJ. Venlafaxine in adults with attention-deficit/hyperactivity disorder: an open clinical trial. J Clin Psychiatry. 1996;57:184-189.
Silver LB. Alternative (nonstimulant) medications in the treatment of attention-deficit/hyperactivity disorder in children. Pediatr Clin North Am. 1999;46:965-975
Spencer TJ, Biederman J, Wilens TE, et al. Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder. Am J Psychiatry. 1998;155:693-695.
Section 1 of 1
Take the Post Test
New Study Shows Prevalence of ADHD May Be Underestimated
from Brown University Child and Adolescent Behavioral Letter
www.medscape.com, 3/20/02
Introduction
School and public health officials may be greatly underestimating the public health impact of childhood ADHD, according to a new study supported by the National Institute of Environmental Health Sciences (NIEHS).
Researchers at the NIEHS in North Carolina reported that when they surveyed parents in a typical county of rural and suburban communities -- Johnston County, N.C. -- the parents reported that more than 15 percent of boys in grades 1 st through 5 th had a diagnosis of ADHD, with about 10 percent (two-thirds of those diagnosed) receiving medication for the disorder.
According to the study authors, treatment rates are considered abnormally high if they exceed the prevalence estimate of three to five percent outlined in a 1994 American Psychiatric Association manual. "Therefore, the national public health impact of ADHD may be greatly underestimated by educators and public health officials," say the researchers.
Including parents in the study was a key to the higher reported rates, the researchers wrote, because school nurses might not be aware of some students who take their medication at home.
The study was based on parent and teacher reports concerning 6,099 children in 17 public elementary schools.
Among the study's findings:
607 children -- 10 percent of the sample -- had received an ADHD diagnosis, 434 of whom were currently receiving medication treatment for the condition (93% stimulants).
About 5 percent of the girls in Johnston County were diagnosed with ADHD, compared to 15 percent of the boys. Also, three times as many boys as girls take medication to treat the condition.
While the percentage of children diagnosed with ADHD was similar among African-American and White children, medication treatment rates were higher among White children -- particularly boys -- compared with African-American or Hispanic children (8%, 5% and 2%, respectively).
Medication treatment rates also increased with grade level, with more than nine percent of children in 4 th and 5 th grades receiving medication for the disorder.
The authors could not explain why smaller proportions of African-American and Hispanic children with ADHD were receiving medication compared to white children. They cited increased barriers to care, including less access to providers, less health insurance coverage and less ability to pay for medications, as well as cultural differences toward the use of medications, as possibilities.
Possible Impact of Findings
Study author Andrew Rowland, Ph.D., told The Brown University Child & Adolescent Behavior Letter that these findings raise important public health questions regarding diagnosis and treatment of childhood ADHD.
Rowland, an epidemiologist at the University of New Mexico in Albuquerque, said, "If so many children are receiving medication, the public health questions become: Are they appropriate candidates for the treatment, are they benefiting from the treatment and, is follow-up adequate?"
The results of this study add fuel to ongoing concerns that too many children are being treated for the disorder. Rowland agrees that medication treatment is very helpful for children with ADHD but at the same time he stresses the need for standardized diagnosis and good follow up.
"Results of the MTA study suggest that medication treatment for ADHD works much better if there is good follow up of the child being treated and regular interaction between the doctors providing the treatment, the schools and parents," explained Rowland.
Standardization of diagnoses is perhaps the first piece of the puzzle. Rowland cites a report from the primary care network that suggests that 62 percent of primary care physicians do not use DSM criteria to diagnose ADHD (Wasserman, 1999).
"A more recent report from the Academy of Pediatrics suggest that this is something that should change," says Rowland.
Rowland also points to the need for accurate national prevalence data.
"I believe that the 3-5 percent prevalence estimates for ADHD are outdated and poorly documented. DSM-IV expanded the definition of the disorder when they included inattentive children, which increased prevalence simply by changing the definition," he said. "Our experience in Johnston County is that if we apply DSM-IV criteria the best we can ... the prevalence is several times the 3-5 percent cited in DSM-IV."
To really assess whether these results were merely unusual, or perhaps the sign of higher prevalence rates and medication use, there is a great need for other studies like this one.
"Having that information is important for understanding the dimensions of the impact of ADHD," concludes Rowland.
Rowland AS, Umbach DM, Stallone L, et al.: Prevalence of medication treatment for attention deficit-hyperactivity disorder among elementary school in children in Johnston County, North Carolina. Am J Public Health 2002 92: 231-234.
Reprint Address
Correspondence to: Dr. Rowland, MPH Program, Department of Family and Community Medicine, University of New Mexico Health Sciences Center, 2400 Tucker NE, Albuquerque, NM 87131-5267; e-mail: arowland@salud.unm.edu
Steven C. Stoner PharmD, BCPP Disclosures
Prior to initiating a pharmacologically based treatment approach for attention-deficit hyperactivity disorder (ADHD), one must ensure that an accurate diagnosis has been made. This includes ensuring that the diagnostic criteria described in the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) are met.[1] It is important to obtain adequate and complete histories from family members, caregivers, and teachers to assist in providing an overall, comprehensive evaluation. Additionally, a baseline level of functioning should be established by using 1 or more of the numerous ADHD psychometric assessment scales that are available (eg, Conners scale).[2]
Including family members or assigned caregivers in the initial discussions of initiating medication is also very important. Often children with ADHD will look to their caregiver for guidance and understanding. The caregiver's attitude toward medication is often the determining factor as to whether or not a child will accept and be compliant with medication. Discussing the potential benefits and risks of medication is vital to the eventual outcome of the medication trial. It is also important to not ignore the other facets of treatment for ADHD. Although cognitive behavioral therapy is largely unsuccessful, it is important to use other methods of behavioral therapy, including the use of a reward system for positive behavior.
The mainstay for years in the management of ADHD has been the use of stimulant therapy. Methylphenidate (Ritalin) is the stimulant with the most extensive database of clinical trials providing efficacy, safety, and tolerability data.[3-8] There is also ample and growing evidence with dextroamphetamine (Dexedrine), the combination product of d- and l-amphetamine (Adderall), and pemoline (Cylert) (Table).[3-8] Recently there have been some new advancements in the methods and rates of drug delivery for methylphenidate.
|
Stimulant Medication |
Brand Name |
Dosage Form(s) Available |
|
Methylphenidate |
Ritalin |
5-, 10-, and 20-mg tablets |
|
Methylphenidate sustained release |
Ritalin SR |
20-mg tablet |
|
Methylphenidate extended release (OROS delivery system) |
Concerta |
16-, 36-, and 54-mg caplets |
|
Methylphenidate extended release |
Metadate |
10- and 20-mg tablets |
|
Dextroamphetamine sulfate and saccharate/ amphetamine sulfate and aspartate |
Adderall |
5-, 10-, 20-, and 30-mg double-scored tablets |
|
Dextroamphetamine |
Dexedrine |
5-, 10-, and 15-mg sustained release capsules 5 and 10 mg tablets 5 mg/ml elixir |
|
Pemoline |
Cylert |
18.75-, 37.5-, and 75-mg tablets 37.5-mg chewable tablet |
Recently released is the extended-release preparation of methylphenidate known as Concerta.[9] Concerta uses the OROS drug delivery system, which is an oral osmotic delivery system formulation. The medication consists of a semipermeable rate controlling membrane that surrounds an osmotic core. The medication is coated with an immediate-release form of drug and contains a triple layer of drug inside the membrane. One of the inner layers is considered to be a "push" dose. Water enters the membrane and dissolves the drug, which is then released at a controlled rate through one of the laser-drilled holes in the membrane. Concerta is designed to have a 12-hour duration of action and is available in 18-mg, 36-mg, and 54-mg caplets. Concerta should be used with caution in cases of potential gastrointestinal obstruction, as the semipermeable membrane does not dissolve and passes through the gastrointestinal tract and is eliminated with different excipients inside the capsule. Pharmacokinetically, Concerta has been studied against sustained-release and immediate-release methylphenidate, and no significant differences have been found. Numerically, the Cmax was lower and the Tmax was slightly longer with essentially an equal area under the curve. To date, over 400 patients have been treated in blinded, placebo-controlled trials and Concerta has been found to be equally efficacious with immediate-release methylphenidate.
Additionally, another extended-release form of methylphenidate (Metadate ER) has become available in 10-mg and 20-mg tablets.[10] Metadate ER is designed to have approximately an 8-hour duration of action with the goal to use once-daily dosing. Pharmacokinetic studies comparing both the sustained-release and immediate-release forms of methylphenidate have shown that Metadate ER was more slowly but just as extensively absorbed. The Cmax, Tmax, and AUC were found to be equivalent with sustained-release methylphenidate. Additionally, when taken with food, the Cmax of Metadate ER was found to increase. Metadate ER is to be used in place of immediate-release methylphenidate when the 8-hour dose of Metadate ER corresponds to the titrated 8-hour dose of immediate-release tablets.
Pemoline (Cylert) continues to be a viable option, but is often considered as a later option for the treatment of ADHD in patients who have failed trials with methylphenidate and dextroamphetamine.[7,8] The primary reasons for this include the possibility of hepatotoxicity, which requires twice monthly liver function test monitoring, and its delayed onset of effect, usually as long as 2 weeks. An advantage of Cylert is that it can be dosed once daily.
The dosing of stimulants has been an issue with clinicians over the years. The controversy has centered on a weight-based dosing model vs empiric dosing. According to recent clinical trials, efficacy has not been greatly associated with the weight-based model, and more clinicians prefer to use an empiric dosing approach.[11] Typically, methylphenidate is initiated at 5-10 mg per day in divided doses, with increases of 5-10 mg per week to a maximum of 60 mg/day. Dextroamphetamine is typically dosed at 2.5-5.0 mg per day, with increases of 5 mg every week to a maximum dose of 40 mg/day. Adderall (dextroamphetamine/amphetamine) is typically initiated at 5-10 mg per day in children 6 years of age and older, and at 2.5 mg per day in children from the ages of 3-5 years. Pemoline is usually started at 37.5 mg per day and is increased by 18.75 mg on a weekly basis, depending on response, to a maximum of 112.5 mg per day.
Additional therapies that have been studied but that are not yet widely used include antidepressants (bupropion, tricyclic antidepressants [TCAs], monoamine oxidase inhibitors [MAOIs], selective serotonin reuptake inhibitors [SSRIs]), and the alpha agonists clonidine and guanfacine.[5-8,12,13]
The side effects from stimulants are very similar among the different available agents. Those side effects include insomnia, anorexia, weight loss, nausea, hypertension, tachycardia, gastrointestinal distress, growth suppression, tic development, psychosis, mania, rash, headache, and a potential of lowering the seizure threshold.[5-8]
Drug interactions are also a potential concern with stimulant medications. Stimulant use with MAOIs should be avoided concurrently and also within 2 weeks of using an MAOI. Additionally, there is concern about using other classes of antidepressant medications, including the TCAs, which have the potential for cardiac-related adverse events. Stimulants have also been associated with increasing clotting times in patients who are treated with warfarin. Additional precaution should be taken when stimulants are taken with over-the-counter cold preparations that contain systemic decongestants.
Predicting who will respond to stimulant therapy remains something that clinicians are not able to determine. Response is generally measured by a decrease in motor activity (eg, reduced activity to normal, improved fine motor control), improvement in social interactions (eg, decreased anger and increased ability to play with others), and improved cognitive functioning (eg, increased sustained attention, reduced distractibility).
The Texas Children's Medication Algorithm Project has attempted to provide a set of guidelines to assist the clinician with a standardized method to treat ADHD alone and when several comorbidities are present.[7,8] The guidelines have been established from an extensive literature search and an assessment of the available data. For classic ADHD, inattentive or hyperactive-impulsive type, the stimulants methylphenidate or dextroamphetamine are recommended as first line.[7,8] If no response is obtained after 2 weeks, it is recommended to switch to the other stimulant.[7,8] For ADHD with comorbid anxiety or depression, a stimulant is used as the first-line therapy for a minimum of 2 weeks.[7,8] If ADHD improves, but depression does not, then it is recommended that an antidepressant, preferably an SSRI, be added.[7,8]
Until recently, a major area of ADHD research that was lacking was clinical data showing head-to-head efficacy comparisons between stimulants. The last 2 years have produced some clinical efficacy evidence comparing dextroamphetamine/amphetamine (Adderall) and methylphenidate (Ritalin).[14-17 ] There continues to be no comparative trials of extended-release methylphenidate vs sustained-release methylphenidate, sustained-release methylphenidate vs dextroamphetamine/amphetamine, extended-release methylphenidate vs dextroamphetamine/amphetamine, or dextroamphetamine vs dextroamphetamine/amphetamine.
Methylphenidate and Adderall were tested in school-aged children (range, 5-17 years) with ADHD.[14] Subjects participated in a 4-week, double-blinded, placebo-controlled trial in which the treating psychiatrist was allowed to determine which stimulant the child would be prescribed. One hundred fifty-nine subjects were referred for treatment, 117 of whom were placed on methylphenidate and 42 of whom were placed on Adderall. Subjects received a placebo dose, and varying doses of either methylphenidate (5 mg, 10 mg, or 15 mg by mouth twice daily) or Adderall (5 mg, 10 mg, or 15 mg by mouth every day). Subjects were then matched to the 42 Adderall subjects based on age, length of treatment, and gender. Results of this trial showed that the best dose of each agent was 19.5 mg per day of methylphenidate and 10.6 mg per day of Adderall. Both agents were considered to be more effective than placebo based on both parent and teacher ratings.
|
Adderall |
Methylphenidate |
|
|
n |
42 |
117 |
|
Best dose |
10.6 mg qd |
19.5 mg / d |
|
Superior to placebo? |
Yes |
Yes |
|
side effects |
> insomnia, mood changes |
> anxiety |
|
Findings: |
The findings of this study provide evidence that once daily dosed Adderall is at least as efficacious as twice-daily methylphenidate. |
|
Side-effect reports were similar for both agents, with methylphenidate subjects reporting more anxiety and Adderall subjects reporting more insomnia and changes in mood. Notably, 15 subjects who received Adderall had been considered treatment failures on methylphenidate, 13 of whom responded. The findings of this study provide evidence that once daily dosed Adderall is at least as efficacious as twice-daily methylphenidate. The study was not without limitations, which included a nonrandom assignment of patients to treatment arms and the use of primarily middle-class subjects. Additionally, those who had not responded to methylphenidate may have benefited from the increased attention they received during the trial, thus increasing their likelihood of response.
|
Adderall |
Methylphenidate |
|
|
n |
25 |
25 |
|
Superior to placebo? |
Yes |
Yes |
|
side effects: |
> mood changes (sadness) |
|
|
Findings: |
Adderall was found to significantly improve social behavior over Ritalin |
|
Another comparative trial between Adderall and Ritalin studied the efficacy and time course to response in children with ADHD.[15] The trial evaluated 25 subjects who were enrolled in a 6-week, within-subject, double-blind, placebo-controlled, crossover-designed trial. All subjects concurrently participated in an intensive behavioral treatment program. Subjects received placebo, Ritalin 10 mg or 17.5 mg by mouth twice daily, and Adderall 7.5 mg or 12.5 mg by mouth twice daily. Medications were changed daily at random so that each subject received an average of 5 days on each dose being evaluated. Ritalin and Adderall were considered to be more effective than placebo on all measures, including in the classroom and at recess. Adderall was found to significantly improve social behavior over Ritalin. Counselors and teachers felt that the higher dose of Ritalin and the low and high doses of Adderall were equally effective. Additionally, the authors concluded that using a reduced midday dose of stimulant would be effective for stimulants that require twice-daily dosing. Adderall was also reported to have a larger effect size during the fifth hour after the morning dose when compared with Ritalin. Adderall was reported to result in more side effects, which included gastrointestinal upset, loss of appetite, insomnia, changes in mood, and headache. Surprisingly, though, at the conclusion of the study more subjects were recommended to continue on the low dose of Adderall (n = 11) than on the high dose of Ritalin (n = 4). The primary limitation of this trial is that nonequivalent doses (3:4 ratio) of Adderall and Ritalin were used.
In a 3-week, double-blind, placebo-controlled study, Adderall was again compared to methylphenidate in children (mean age = 8.1 years) diagnosed with ADHD.[16] Fifty-eight subjects were randomly assigned to receive placebo (n = 18), Adderall (n = 20), or methylphenidate (n = 20). Subjects were dosed according to specific dosing algorithms, with dosage adjustments made at the end of each week. Both stimulants were found to be superior to placebo according to psychiatrist and teacher ratings, while parents found no difference between stimulants in their evening assessments. Again, the side-effect profiles for both stimulants were similar, with more Adderall-treated subjects reporting changes in mood (sadness) and gastrointestinal upset. The mean doses during the trial were 25.2 mg per day for methylphenidate and 12.5 mg per day for Adderall. Again, this trial was potentially limited by restrictions on methylphenidate dosing according to the algorithm and the relatively short 3-week duration of the study.
The future study of ADHD looks very promising. With a new dosage formulation of methylphenidate coming to market, one can expect an increase in the number of comparative trials between once-daily dosed Adderall and once-daily dosed methylphenidate. Research for all stimulants to date shows a very robust response rate, estimated to be nearly 60% to 70%. Selection of therapy is often dependent on family history of response, physician familiarity, and comfort level with a particular medication, issues of compliance, and issues of cost. While methylphenidate continues to be commonly prescribed, in part due to its efficacy and in part due to the availability of a generic formulation, the newer agents are certainly a viable treatment option in cases where frequent dosing and intolerability are of concern.