Attention-Deficit Hyperactivity Disorder (ADHD) Medication: A Growing List of Choices.
by Ernest J. Bordini, Ph.D.
Clinical Psychology Associates of North Central Florida
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With the television ads promoting medicine for adult ADHD, the evening news raising warnings about mediation recalls, and concerns about ADHD medication overprescription, the controversies about ADHD and medication becomes a renewed conversation in many families. There will always be those opposed to any psychoactive medication for children and those who see a pill as a solution for everything. This article hopes to provide some basic information about the diagnosis of ADHD and the role of medication in treatment. The role of stimulant medication, newer FDA-approved ADHD medication, as well as a brief review of some medications which are more rarely used for ADHD.
Attention-deficit Hyperactivity Disorder (ADHD) is not a new diagnosis. It was referred to as hyperkinesis, minimal brain damage and Attention-deficit Disorder (ADD) with and without hyperactivity in the past. The current nomenclature consists of ADHD predominantly hyperactive-impulsive type, predominantly inattentive type, and combined type. It is the most common neurodevelopmental psychiatric disorder. Males are diagnosed more frequently than females, and scientist agree that there is a genetic component in many cases. The primary symptoms are levels of overactivity, difficulty sustaining attention, difficulty completing tasks such as homework and disorganization which are problematic relative to age peers and result in difficulties in functioning. The symptoms need to be present since childhood.
Since there are no symptoms of ADHD that are unique to ADHD and the main question is are the problems unusual for age and ability it is easy to over-diagnose or under-diagnose the disorder. Since the disorder is one that persists into adulthood, diagnosis has serious implications for school, current and future medical insurance costs, and involves consideration of possible long-term medication. In addition other disorders such as handwriting difficulties, other behavior and mood difficulties often co-exist. Clearly, this diagnosis warrants careful psychodiagnostic evaluation. More information about symptoms and assessment is available at ADHDASSESSMENT.COM, CPANCF.COM and CHADD.ORG.
The National Institute of Mental Health conducted large study, called the Multimodal Treatment Study of Children with ADHD, involved close to 600 children with ADHD treated fir a 14-month period. Children who were treated with medication alone, and children who received both medication management and behavioral treatment had the best outcomes with respect to improvement of AD/HD symptoms. Combination treatment provided the best results with respect to ADHD and other areas of functioning (Swanson et. al., 2001).
While some children may get by with accommodations, many have sufficiently severe difficulties that they will require medication. Fortunately, studies are generally consistent with the American Academy of Pediatrics findings that 70-80% of children respond positively to medication. However, it also emphasizes use of behavior therapy such as parent training and group sessions. The American Academy of Child & Adolescent Psychiatry (1999) also emphasizes that psychiatric medication should not be used alone for ADHD or other conditions. It states that medication should be part of a more comprehensive approach and treatment plan that usually includes psychotherapy as well as parent training or involvement in the therapy.
By far the most frequently prescribed medication for ADHD in children are psychostimulant medications. This is not new. Since stimulant were first administered to children with behavior and learning problems in the late 1930's. At first it was thought that the stimulants had a paradoxical effect, calming hyperactive children.
We now understand that stimulant medication increase certain neurotransmitters which act to improve the brains ability to inhibit and control behavior and to focus and shift attention. Stimulants increase the brain’s neurotransmitter levels of dopamine, norepinephrine, and serotonin, usually on a short-term basis (3-5 hours). Higher levels of dopamine are believed to reduce hyperactivity, while an increase in norepinephrine improves attention.
I often use the analogy of adding steering and brake fluid to an automobile. All the parts may be there, but adding the fluids if they are low makes stopping, starting and staying on the right road much easier than if the levels are critically low. Medications will not make a child a perfect child nor make them do anything they don’t want to do or do not have the abilities to do. Thus the importance of assessment for establishing appropriate expectations and parent training and child therapy for dealing with motivational or behavioral issues.
There is now nearly eight decades of research and clinical experience which have demonstrated stimulants are generally safe and effective as prescribed. Studies have demonstrated reduced levels of out-of-seat behaviors, improved on-task performance and reduced distractability, fewer spelling and math errors, and even improved handwriting. What is relatively new, are a variety of stimulants with slow release forms, and a new non-stimulant medication. Though a slow-release stimulant (Ritalin SR) had been around for some time, it was reported to be somewhat unpredictable in terms of duration, and did not become as popular as the newer slow-release stimulant preparations. Some of these newer medications are quite sophisticated in terms of their release mechanisms, allowing for an immediate dose, and a second release in 3-4 hours.
An older medication, Cylert (magnesium pemoline) was a frequent alternative medication to shorter-acting medication and was often used in ADHD children who developed tics with other stimulants. Unfortunately often did nor produce a therapeutic effect for 3-4 weeks. Since regular blood work is necessary due to more serious risks of liver failure and sometimes high blood pressure, this is now rarely used and never became as popular as the current long-acting stimulant medication.
It is important to note that despite the multitude of stimulant medications, the American Academy of Pediatrics has found that each stimulant improved core symptoms equally. Thus, the differences largely involve absorption rates which effect blood levels which are important to the type of effect the stimulants have and how long the medication lasts.
Dexedrine (dextroamphetamine sulfate, Dextrostat) Ages 3+ Duration 4-5 hr Onset 20-30 min. introduced in 1950s
Longer acting medications avoid the necessity to be called out of class for medication during the school day. Longer-acting stimulants may also help with completion of homework after school. In some cases a child is switched to a longer-acting stimulant to reduce some of the side effects such as afternoon irritability resulting from more rapid decreases in the stimulant blood level from short-acting doses. The trend toward the use of longer acting medication for ADHD is also probably partially due to increased awareness that problems in impulsiveness, inattention, hyperactivity impact on peer and family relationships as well as extracurricular activities.
Clinical use of the longer-acting stimulants have led some to report that individual duration of the effective response can vary from the duration the medications are designed for. Thus, in the accompanying table in this article a range is given.
Stimulant and other medications sometimes do have side effects, though opponents to psychoactive medication for children often make wild claims. Stimulants do reduce appetite and therefore some weight loss or failure to gain an expected amount of weight can be seen if care is not taken to provide a good breakfast before the morning dose and sometimes shift meals to a later time. Research also show that children generally regain growth when off the medication.
The second most common misconception is that stimulants turn children into “zombies”. Proper doses of medication increase concentration, decrease hyperactivity and seem to exert a calming effect, sleepiness or unresponsiveness is not typical unless the child is greatly over-medicated. When discussing side effects, it is important to understand all medication have side effects -just take a look at the side effects for aspirin or Tylenol. As with any medication, a small number of children can show unusual reactions, but since the medication is relatively short-acting these are usually short-lived. Other side-effects such as headaches and irritability usually disappear after a week or two. Sleep onset difficulties can occur if the medication is taken too late in the day or lasts too long, but with properly scheduled dosing this should not be a problem.
Some physicians were reluctant to prescribe stimulants in individuals who tended to be anxious, since the stimulants increase physiological arousal. Clinical experience has largely found this to be only true for more severe anxiety disorders, and mild levels of anxiety usually do not contra-indicate stimulant use if an accurate diagnosis of ADHD is made. As co-existing disorders may influence which medication may be selected for treatment, it is important to perform a comprehensive assessment.
A final misconception is that children treated with stimulant medication will become addicted or will abuse other drugs later in life. Follow-up studies generally indicate this is not true, and some studies find untreated children are more likely to abuse drugs in later life. It is likely that children with ADHD and who also show oppositional or conduct problems constitute a high-risk group for drug abuse as well as other illegal and destructive behaviors in later adolescence and adulthood. This highlights the importance of parent training to reduce oppositional behavior as early as possible to prevent evolution into more serious conduct problems which can be quite difficult to treat.
Common Stimulant Side Effects
-trouble getting to sleep
-restlessness or irritability
- drowsiness or excessive staring (rare)
-tics (involuntary motor movements; rarely chronic; sometimes temporary)
- hallucinations or bizarre behavior (rare)
Canada has withdrawn approval of Adderal due to concerns about reports of heart problems and sudden deaths. It remains approved in the U.S. and unlikely will be subject to closer scrutiny for these complications.
Common Stimulant Medication Used to Treat ADHD
Dexedrine Spanules, Ages 3+, Duration 6-12 hrs, somewhat variable duration, initial release 1 hr and 2nd release in 3-4 hrs
Ritalin (methylphenidate); Ages 6+; Duration 4 hrs; Onset of action 15-20 min, introduced in the 1950s
Ritalin SR (methylphenidate); Ages 6+; Duration 3-6 hrs; duration reported to vary greatly
Methylin Chewable Tablet and Oral Solution (another form of methylphenidate)
Methylin ER; introduced 2000
Cylert (pemoline); Ages 6+; long-acting; concerns about liver toxicity
Adderall (dextroamphetamine & levoamphetamine); ages 3+; duration 3.5 - 8 hrs
Adderall XR; ages 6+; duration 8-10 hrs; initial release 1 hrs with additional release 3-4 hrs; introduced in 2001
Concerta (methylphenidate); ages 6+; duration 10-12 hours; introduced 2000
Metadate ER (methylphenidate); duration 8 hrs; has two peaks; introduced 2000
Metadate CD (methylphenidate); smoother curve than CD; introduced in 2001
Ritalin LA (methylphenidate); duration 8 hrs; 1/2 released initially and ½ in 4 hrs
Focalin (dextro-methylphenidate hydrocholoride); more potent than levo-methylphenidate and wice as potent as methylphenidate
Provigil (modafinil); 15 hour half-life; released in 1998
Nuvigil (made of one of the isomers of Provigil); longer-acting than Provigil; possible release (2006)
Tricyclic antidepressants were long known to be effective for treating depression, also by increasing neurotransmitter levels. These were also often used, though not necessarily FDA-approved for an alternative means of treating ADHD children who developed tics, could not otherwise tolerate stimulants, who may have some co-existing problems such as insomnia, bedwetting, depression, or anxiety, or whose parents feared Ritalin might turn their children into the dreaded “green zombie”. However, these medications were more inherently dangerous than the stimulants since overdose raised serious issues of cardiac arrest. Though many children were safely treated a small number of cardiac-related deaths were reported, some of which involved children who had cardiac problems. This, combined with safer new antidepressants, the Selective Serotonin Re-uptake Inhibitors (SSRI’s) such as Prozac, greatly reduced the use of these medications in children.
Common tricyclic antidepressants included imipramine, desipramine, amitryptiline, Nortriptyline and Clomipramine. Side effects were lowered blood pressure, irregular or rapid heartbeat, fatigue, stomach upset, dizziness, dry mouth, with some medication sleep difficulties, and rarely confusion and seizures. Abruptly stopping the medication could result in increased blood pressure, agitation and sleeplessness.
Selective Serotonin Re-uptake Inhibitors (SSRIs)
The popularity of the tricyclic antidepressants began to wane with the introduction of medications such as Prozax (fluoxetine) which were effective in more selectively targeting Seretonin, the SSRIs. These have not been FDA approved for ADHD, and like the tricyclics, probably were less effective at treating some of the core symptoms of inattention and hyperactivity than the stimulants.
Common SSRI side effects are constipation or diarrhea, sometimes nausea, headaches or dizziness, and in adults and late adolescents, sexual side effects could occur. Sleep is sometimes improved, but the more activating SSRIs are sometimes associated with sleep onset difficulties. These generally may take 3-5 weeks to reach full effect, and are sometimes started with a low dose to reduce the initial side effects. The effects of the medication are long-tern. At first it was thought that rapid discontinuation of these was far less problematic than the older antidepressants, but similar reaction have been reported especially for the SSRIs which have a shorter half-life.
Not all of the SSRI’s are alike, some tend to be more activating and some tend to be more sedating. For example Effexor (venlafaxine) has effects on both serotonin and norepinephrine. Serotonin is believed, among other things, to have an important role in depression. Use of these medications as second-line medications for treating ADHD began as the popularity of tricyclic antidepressant use for children waned. More recently there have been some warnings concerning use of Paxil or Zoloft with children. As with the tricyclics, not all have been FDA approved for children or adolescents. Refer to the CPANCF.COM Articles and Archives section for a more detailed discussion of the controversy about antidepressant use in children.
Wellbutrin (bupropion hydrochloride) stimulates dopamine, but may be less effective than stimulants with respect to core ADHD inattentive symptoms. It has been FDA approved for treatment of depression and to help stop cigarette smoking (also marketed as Zyban). It is relatively short-acting from 4-6 hours, with longer acting forms available which may last 6-8 hours. Though not FDA approved for ADHD or children under 18, use of Wellbutrin became popular for treatment of adolescent and adult ADHD since it was not a controlled substance and tended to be of some help with mood problems. Common side effects include insomnia and headaches.
Another alternative to stimulants evolved with the use of medication that was traditionally used to lower blood pressure, the anti-hypertensive medication. This class of drugs can be very dangerous if there is an overdose, due to the effect on the cardiovascular system.
Catapres (clonidine), which blocks norepinephrine auto-receptors probably became the most popular of these, though it also is not FDA approved for ADHD. Medication effects last 4-6 hours, though a patch also became available which was designed to last 5-6 days. Clinical experience suggested that it tended to help more with hyperactive and impulsive or explosive behavior, and in some cases it was prescribed with an antidepressant or stimulant in difficult cases. Tenex (guanfacine) which lasts 6-8 hours, like clonodine seemed to work on anger and hyperactivity more than inattention. This also was not FDA approved for ADHD. Use began to wane to a degree after a report of a small number of deaths when combined with Ritalin. These medications tended to produce drowsiness and had to be discontinued slowly. Common side effects were dry mouth, headaches and nausea. Since these are used to lower blood pressure, cardiac evaluation should be performed prior to prescription. Blood pressure and heart rate should be periodically monitored.
Provigil(modafinil), released in 1998, is a medication seeing increased use for ADHD. It's manufacturer is in the process of obtaining approval for treatment of ADHD (possibly 2005). It is a drug traditionally used to treat narcolepsy and the fatigue associated with sleep apnea. Successful double-blind placebo-controlled studies and studies in adults have been reported.
It is presumed Provigil has its main effect on the hypothalmus and seems to improve alertness without some of the side effects of more traditional stimulants. It is an Alpha1-adrenergic agonist and believed to increase the receptiveness of brain's alpha-1 receptors to the neurotransmitter noradrenaline resulting in increased alertness, memory and energy. Common side effects are reported to include headache, nausea, diarrhea, upset stomach, headache, nausea, nervousness, anxiety, trouble sleeping, dizziness, or back pain. It may reduce the effectiveness of birth control pills.
Selective Norepinephrine Re-uptake Inhibitor
Strattera (atomoxetine) was FDA-approved in 2002. It is an ADHD medication which inhibits pre-synaptic re-uptake of norepinepherine. It is FDA approved for ages 6 and above. While some studies show it is as effective as the stimulants and tolerated as well as the stimulants there are some greater cautions. Strattera should not be taken with MAO–inhibitors, and there are some cautions regarding individuals with either high or low blood pressure and for those with kidney or liver difficulties. There are some reports that it may also improve mood or mood swings, particularly with higher doses. Though response is immediately seen with stimulants, full effects with Strattera may not be seen for 3-4 weeks. It is long-lasting and around-the-clock response can be achieved with one or two doses a day.
Strattera side effects are not unlike other stimulants or some of the antidepressants and consist of some reports of headache and sometimes dizziness, gastro-intestinal complaints such as stomach aches, nausea or vomiting and decreased appetite, dry mouth. While improvement in mood is usually seen, some individuals reported mood swings and/or fatigue and some reported nervousness or sleep difficulties. Some adults experience difficulty with urination, erectile difficulties, prostate difficulties, menstrual irregularities, or insomnia.
Mood stabilizers are sometimes used when other approaches fail or when there seems to be cyclical mood changes. Increased use seems to be associated with an increasing trend of the diagnosis of bipolar disorder in children and adolescents, a very controversial topic. While it is true that a greater than average number of ADHD children and adolescents will develop bipolar disorder (manic-depression) in adulthood, a full clinical presentation of Bipolar Disorder - Type I is uncommon before early adulthood. Since hyperactive symptoms and even inattentive symptoms overlap a great deal with manic symptoms, and only a short duration is required to diagnosis a brief manic episode referred to as a hypomanic episodes, it is easy to misdiagnose ADHD and Bipolar Type II. Like ADHD, this is assumed to be a chronic disorder, but with more severe consequences and implications in adulthood with respect to potential employment, functional outcome, and even the ability to obtain future health insurance.
Since the risk of overdiagnosis of bipolar in ADHD children is high and the implications serious, some people have been critical and feel that this is rapidly becoming the “fad” alternative diagnosis in ADHD children. In the author’s opinion this should only be diagnosed after careful psychiatric and psychological evaluation.
Some of these medications such as carbamazepine (Tegretol or Epital), Topamax (topiramate), Lamictal (lamotrogine) and gabapentin (Neurontin) all act and have been used as anticonvulsants (used for seizure control) and mood stabilizers. There has been some clinical use for ADHD, though these also are not FDA approved for ADHD. It must also be noted that some of these medications can actually interfere with certain types of motor and cognitive performance and carry a number of more serious warning and side effects than the stimulants.
Finally, there is very little support that supplements, vitamins, food additives have any general use in effective treatment for ADHD children. While there may be very few children who have a particular response to medication, the marketing of these products is understandable. Many people fear traditional medicines and the large market created by this frequently diagnosed childhood condition attracts all sorts of snake-oil vendors, unlicensed helpers, and unproven and often costly treatments. As a general guide, if results are promised, a treatment is touted as a cure-all for a wide variety of conditions, dramatic improvements described in testimonials, or the individual providing the service is not licensed by the state, caveat emptor (buyer beware).
American Academy of Child & Adolescent Psychiatry (1999)
Swanson, J.M., Kraemer, H.C., Hinshaw, S.P., Arnold, L.E., Conners, C.K., Abikoff, H.B., et al. (2001). Clinical relevance of the primary findings of the MTA: Success rates based on severity of ADHD and ODD symptoms at the end of treatment, Journal of the American Academy of Child and Adolescent Psychiatry, 40, 168–179.
Kratochvil CJ Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial. 2002, -J Am Acad Child Adolesc Psychiatry 41(7): 776-84.
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Disclaimer: Note the information contained in this article is offered only as general education and is not intended to offer medical or psychological advice. Consult your physician and pharmacist about the latest information about dangers, effects, and side effects of any medication. Dr. Bordini is Executive Director of Clinical Psychology Associates of North Central Florida (CPANCF.COM) and an adult and pediatric neuropsychologist who specializes in assessment of ADHD as well as head injuries.