Understanding ADHD | For Professionals | For Healthcare Professionals | Treatment Strategies | The Role of Medication

The Role of Medication

Medication is an integral part of treatment for many children and adults with ADHD. Medication does not cure ADHD; when effective, it eases ADHD symptoms during the time it is active.

Medications that most effectively improve the core symptoms of ADHD seem primarily and directly to affect certain neurotransmitters. The neurotransmitters involved are dopamine and norepinephrine. Both neurotransmitters appear to play a role in the attentional and behavioral symptoms of ADHD. Use of a medication trial helps determine which medicine works best for each individual and at what dosage. The trial usually begins with a low dose that is gradually increased at 3–7 day intervals until clinical benefits are achieved.

The reports on medication use vary. For some, the benefits are extraordinary; for others, medication is quite helpful; and for still others, the results are more modest. Attention span, impulsivity and on-task behavior often improve, especially in structured environments. Some children also demonstrate improvements in frustration tolerance, compliance and even handwriting. Relationships with parents, peers and teachers may also improve.

Psychostimulant medications

Psychostimulant compounds are the most widely used medications for the management of ADHD symptoms. Psychostimulant medications were first administered to children with behavior and learning problems in 1937. Despite their name, these medications do not work by increasing stimulation of the person. Instead, they help important networks of nerve cells in the brain to communicate more effectively with each other. Between 70–80 percent of children with ADHD respond positively to these medications. In some instances, the first medicine tried may not be the right one, or perhaps a higher dose may be needed.

Common psychostimulant medications used in the treatment of ADHD include methylphenidate (Ritalin, Concerta, Metadate, Focalin); mixed salts of a single-entity amphetamine product (Adderall, Adderall XR); and dextroamphetamine (Dexedrine, Dextrostat). Methylphenidate, amphetamine and mixed salts of amphetamine are now available as both short- and long- acting preparations. Short-acting preparations generally last about 4 hours; long-acting preparations are more variable in duration—with some preparations lasting 6–8 hours and newer preparations lasting 10–12 hours. Of course, there can be wide individual variation that cannot be predicted and will only become evident once the medication is tried.

The specific dose and timing of medication must be determined for each individual. However, there are no consistent relationships between height, age and clinical response to a medication. A medication trial is often used to determine the most beneficial dosage. The trial usually begins with a low dose that is gradually increased at 3–7 day intervals until clinical benefits are achieved. It is common for the dosage to be raised several times during the trial.

In addition, the individual is monitored both on and off the medication. For children, observations are collected from parents and teachers, even coaches and tutors, and parent and teacher rating scales are often used. In all cases, the appropriate dose must be tailored to the individual patient and monitored by the prescribing medical professional to make any needed adjustments.

Short-acting preparations generally last approximately 4 hours; long-acting preparations are more variable in duration—with some preparations lasting 6–8 hours and newer preparations lasting 10–12 hours. Of course, there can be wide individual variation that cannot be predicted and will only become evident once the medication is tried.

Since effective longer-acting formulations of stimulants became available, many children, adolescents and adults have found these preferable. Longer-acting medications may cause fewer “ups and downs” over the day and may eliminate the need for taking additional doses at school or during work. Although there is little research on utilizing short-acting and long-acting medications together, many individuals, especially teenagers and adults, find that they may need to supplement a longer-acting medication taken in the morning with a shorter-acting dose taken in the mid to late afternoon. The “booster” dose may provide better coverage for doing homework or other late afternoon or evening activities and may also reduce problems of “rebound” when the earlier dose wears off.

Hundreds of controlled studies involving more than 6,000 children, adolescents and adults have been conducted to determine the effects of psychostimulant medications—far more research evidence than is available for virtually any other medication. There are no studies on the use of psychostimulant medications for more than a few years, but many individuals have been taking these medications for many years without adverse effects. Longer term controlled studies cannot be done because this would involve withholding treatment over many years from some patients suffering significant impairments, which would be unethical.

Nonstimulant medications

Although stimulants are the best tested and most widely used medications for the treatment of ADHD, some children, adolescents and adults respond just as well or better to treatment with other medications that are not stimulants. Nonstimulants may be used when psychostimulant medications have been ineffective, unacceptable side effects have resulted, or the individual or child’s parents prefer a nonstimulant for other reasons.

Atomoxetine (Strattera) is neither a stimulant nor an antidepressant. It alleviates inattention and hyperactivity/impulsivity symptoms of ADHD by affecting specific aspects of the norepinephrine system. Atomoxetine has been tested on more than 1,600 children, adolescents and adults. It is a prescription medication, but it is not a controlled substance like a stimulant. This allows medical professionals to give samples and to place refills on the prescriptions. It does not start working as quickly as the stimulants do. Reports suggest that the full effects are often not seen until the person has been taking atomoxetine regularly for 3 or 4 weeks. 

Antidepressants

Antidepressants that have a direct effect of increasing the neurotransmitter norepinephrine (but not serotonin as in the selective serotonin reuptake inhibitors [SSRIs] like fluoxetine) appear to have a positive effect on the core symptoms of ADHD. None of the antidepressants has been approved by the FDA for the treatment of ADHD in children, adolescents or adults; such treatment is considered off-label.

Antihypertensive agents

Clonidine (Catapres; Kapvay) and guanfacine (Tenex; Intuniv) are alpha-2 and alpha-2a noradrenergic agents, respectively, that may indirectly affect dopamine by first affecting norepinephrine. Although they have been used to help children who have ADHD with hyperactive and aggressive symptoms, their use in adults has been generally minimal. A few small controlled studies have shown some efficacy of guanfacine in adults with ADHD. However, sedation and blood pressure lowering effects as well as potential hypertensive rebound are issues of concern. Long-acting preparations of clonidine Kapvay and guanfacine have been approved for ADHD in children and may also be helpful in adults.

Wake-promoting agent

Modafinil (Provigil) is approved by the FDA for the treatment of narcolepsy. Its main effect appears to be indirect activation of the frontal cortex rather than direct involvement in central dopamine and norepinephrine pathways. In a two-week, controlled study of modafinil, 48% of adults with ADHD responded favorably to the medication. Longer, controlled studies in adults are clearly needed. At this time, modafinil’s utility may be limited to adults with ADHD who do not respond to first line medications. A variation of modafinil, armodafanil (Nuvigil) has become available in the United States; its effects on ADHD in adults have not yet been studied.

Possible side effects of medications for ADHD

Most immediate side effects related to these medications are mild and typically short term. The most common side effects are reduced appetite and difficulty sleeping. Some children experience stimulant rebound, a brief period of negative mood, fatigue or increased activity when the medication is wearing off. These side effects are usually managed by changing the dose and scheduling for short-acting medications or by changing to a prolonged-release formulation. Headaches and stomachaches can also occur; these often disappear with time or, if necessary, a reduction in dose. Some children may have an initial, slight effect on height and weight gain, but studies suggest that ultimate height and weight are rarely affected. A few studies suggest that some children with ADHD reach puberty later than their peers, but this does not appear to be a result of medication treatment.

Tics are involuntary motor movements, such as eye blinking, facial twitching, shrugging and throat clearing. Sometimes children who are given stimulant medication may appear to develop tics. The medication, however, does not actually cause the tics, but may instead bring them to notice earlier, or make them more prominent than they would be without medication. They often eventually go away, even while the individual is still on medication.

Tourette’s syndrome is a chronic tic disorder that involves vocal and motor tics. Experts estimate that 7 percent of children with ADHD have tics or Tourette’s syndrome that is often mild but can have social impact in the severe but rare form, while 60 percent of children with Tourette’s have ADHD. Recent research suggests that the development of Tourette’s syndrome in children with ADHD is not related to psychostimulant medication. However, a cautious approach to treatment is recommended when there is a family history of tics or Tourette’s syndrome, as certain patients will experience worsening of their tics with stimulant treatment. In these cases, treatment with nonstimulant medications may be considered as an alternative.

Medication therapy in adults with ADHD and co-existing psychiatric disorders    

There is no controlled research on medication therapy in adults with ADHD and co-existing conditions. The treatment decisions of the medical professional and the individual will be guided by their previous therapeutic and clinical experience, extrapolations from others’ clinical experiences, and a rational, empirical approach to the individual’s clinical response.

Significant co-existing conditions are usually treated first, before ADHD, especially if they cause more significant clinical and functional impairment and disturbance. This is particularly true with substance use disorders, severe depression and bipolar disorder, psychoses, and homicidal or suicidal ideation. It is important to consider how the ADHD may be affected by medication for a co-existing disorder—both positive and negative, both helpful and harmful. For example, treating depression with bupropion may also help ADHD. On the other hand, some medications for major depression and bipolar disorder may actually worsen ADHD symptoms. The SSRIs (selective serotonin reuptake inhibitors), which by themselves do not effectively treat ADHD symptoms directly, appear to be successful in the treatment of individuals who have co-existing depression and who are taking stimulants at the same time for ADHD.

It is also important to note that medications for ADHD may affect co-existing disorders. For example, psychostimulants may worsen an untreated anxiety or bipolar disorder. The risk of stimulant abuse is also greater in adults with substance use disorder and are actively using. However, as previously mentioned, successful treatment of ADHD tends to decrease the chances of a person with ADHD eventually developing an SUD.

Some nonstimulant treatments of ADHD may simultaneously and adequately treat the co-existing disorder along with the ADHD. For example, an antidepressant (TCA, bupropion, venlafaxine) may effectively treat co-existing depression and ADHD, and similarly, a TCA or venlafaxine may successfully treat co-existing anxiety and ADHD.