Approximately 10 million adults have attention-deficit/hyperactivity disorder (ADHD). Although there is a significant amount of research on medication treatment for children with ADHD, much less controlled research data has been conducted on medication therapy in adults. As a treatment of ADHD, it has been said that “pills do not substitute for skills.” This means that medication alone is not sufficient to help a person improve his or her problems in areas such as organization, time management, prioritizing and using cognitive aids. However, medication improves attention and reduces impulsivity in adults who have been correctly diagnosed with ADHD. Adults with ADHD may also frequently have other conditions such as depression or anxiety that may require additional treatment.
How medication works
Medications that most effectively improve the core symptoms of ADHD seem primarily and directly to affect certain neurotransmitters (brain molecules that facilitate the transmission of messages from one neuron [brain cell] to another). The neurotransmitters involved are dopamine and norepinephrine. Both neurotransmitters appear to play a role in the attentional and behavioral symptoms of ADHD. Practitioners cannot know in advance what drug will work best for a particular patient without trying them. Doctors will use a medication trial to figure out 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.
Psychostimulant compounds are the most widely used medications for the management of ADHD symptoms in adults as well as children and adolescents. Several long-acting psychostimulants are approved by the Food and Drug Administration (FDA) for the treatment of ADHD in adults and are routinely prescribed. The two stimulants most commonly used, methylphenidate (MPH) and amphetamines (AMP), are regulated as Schedule II drugs by the Drug Enforcement Administration (DEA) because they have a potential for abuse when not used as prescribed by a medical professional. ADHD medications approved for adults include methylphenidate; Focalin, Focalin XR; Concerta; Daytrana; Metadate CD; and the amphetamines, Adderall XR and Vyvanse.
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 withholding treatment over many years from some patients suffering significant impairments, which is required in a controlled study, would be unethical.
Frequently asked questions about psychostimulants
Q. When an adult has been diagnosed with ADHD and decides to seek medical treatment, should the person try MPH or AMP first?
A. There is no scientific basis for choosing one type of stimulant over the other for a given individual who has not yet tried either. Because MPH and AMP affect dopamine and norepinephrine somewhat differently, they also affect people differently.
Both MPH and AMP block the reuptake of dopamine and norepinephrine and increase their levels in the synapse (space where the brain cells connect). AMP also increases the levels of dopamine and norepinephrine in the synapse through another mechanism in the pre-synaptic (pre-connection) brain cell.
If one family of stimulants does not improve ADHD symptoms, the practitioner can try a different type. Because MPH and AMP have different mechanisms of action, combining MPH and AMP may be useful in a person who does not respond to either type alone.
Q. Are adults who take psychostimulant medications more likely to have substance abuse problems?
A. No. Generally, the stimulants are well tolerated in therapeutic doses without any abuse. There is no evidence to substantiate the fear that stimulant use leads to substance abuse or dependence. On the contrary, studies indicate that successful treatment of ADHD with stimulants lowers the chances of substance use disorders, compared to adults with untreated ADHD.
Adults with ADHD who have a co-existing substance use disorder and are actively using sometimes abuse psychostimulants. Generally, the active substance use disorder needs to be treated before the co-existing ADHD can be treated. In this case, it may be advisable not to use a psychostimulant for the treatment of ADHD. For people with a recent history of substance use but no current use, deciding to use stimulant medication needs to be dealt with on a case-by-case basis. Certain extended release preparations, such as Concerta (an extended release form of MPH with an delivery system that cannot be crushed and used other than as prescribed orally), are less likely to be abused.
Q. What are the possible side effects of stimulant use in adults with ADHD?
A. Side effects of stimulant use in adults are generally not severe. For MPH, one controlled study showed side effects such as insomnia, headaches, anxiety, loss of appetite, weight loss (but less weight loss than is seen in children) and some cardiovascular effects. The cardiovascular effects in those with normal blood pressure include increases in blood pressure (systolic and diastolic increases of about 4 mm Hg) and increases in heart rate (less than 10 beats per minute). A few long-term large-scale controlled studies of cardiovascular effects have been published. These studies found that stimulant use was not associated with increased risk of heart attacks, cardiac death or stroke. In addition, a study of adults with well-controlled hypertension showed that ADHD could be safely and effectively managed with mixed amphetamine salts. Regular monitoring of blood pressure is generally recommended in adults with or without ADHD.
Other stimulant treatment considerations
Matching the characteristics of the various extended release stimulants with the needs of the adult requires both knowledge of these medications as well as an understanding of the specific needs of the adult with ADHD and how these needs change over time. It is often useful for the prescribing professional and adult to chart the adult’s needs and individual response to the medication. Adjustments may require changing the amount and/or timing of the dosing, changing the extended release stimulant to one with different characteristics, or adding an immediate release preparation at the beginning, middle or end of the extended release preparation’s action. For example, if an adult has a business meeting later in the day or after dinner, he or she could take the extended release medication later than usual or add an immediate release dose or two late in the day.
With the exception of atomoxetine (Strattera), which will be discussed below, non-stimulant medications have generally been considered second-line medications. They have been used in people who have an incomplete response or no response to stimulants, cannot tolerate stimulants or have certain co-existing psychiatric conditions.
Atomoxetine (Strattera) is approved by the FDA for the treatment of ADHD in children, adolescents and adults. It is a potent selective norepinephrine reuptake inhibitor. It is the first nonstimulant medication to be approved by the FDA for the treatment of ADHD and the first medication of any kind specifically approved for the treatment of ADHD in adults. It lacks the abuse potential of stimulants, and since it is not a controlled Schedule II drug, atomoxetine can be prescribed by telephone and with refills.
While the effects of stimulants are almost immediate, atomoxetine takes longer to produce a response. In controlled studies of adults, atomoxetine was associated with cardiovascular side effects including increased heart rate of five beats per minute and an increase in blood pressure of 3 mm Hg for systolic and 1 mm Hg for diastolic blood pressure. No controlled studies comparing the cardiovascular effects of atomoxetine and of stimulants have yet been published. Other side effects can include dry mouth, insomnia, nausea, constipation, decreased appetite, dizziness, decreased libido, erectile disturbance, and urinary retention, hesitation or difficulty. Atomoxetine may lead, in rare cases, to severe liver injury resulting in liver failure if not stopped immediately on finding any liver effects (itching, dark urine, right upper quadrant tenderness or unexplained “flu-like” symptoms).
In a long-term, open label study of atomoxetine, two-thirds of adults with ADHD continued to have a positive therapeutic response through an average of 34 weeks.
Atomoxetine is metabolized (broken down) in the liver by the CYP2D6 enzyme. Drugs that inhibit this enzyme, such as fluoxetine, paroxetine and quinidine, can inhibit this enzyme and slow the metabolism of atomoxetine. Decreasing the dosage of atomoxetine may be necessary when the person is taking these medications. Atomoxetine (as with the stimulants and TCAs) should not be taken with a mono-amine oxidase inhibitor (MAOI) or within two weeks of discontinuing a MAOI. Likewise, treatment with a MAOI should not be initiated within two weeks of discontinuing atomoxetine.
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.
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.
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.
Choosing a medication
It is crucial for individuals to work with their health care professional to match their needs with the characteristics of the ADHD medication. The process of choosing a medication should involve recognizing the negative side effects of a medication so that the risks and benefits can be adequately weighed in the decision. It is often useful to construct a daily timeline of the needs (both attentional and behavioral) of the adult.
For example, an adult who has severe ADHD symptoms that threaten his/her job may also have difficulty controlling his/her hypertension. In this case, choosing a treatment for ADHD that has a significant effect during the most crucial hours of the work day but does not destabilize the tentatively controlled hypertension will require knowledge of the medications’ actions over time as well as their cardiovascular side effects.
Monitoring the effects of medication
Monitoring the effectiveness of medication over time is important and may require substantial effort. However, fine tuning of the timing and dosing of the medication can often improve the time-related clinical response. Sometimes the prescribing professional alone may fulfill these functions; sometimes an experienced therapist who is familiar with the adult can provide additional input to help maximize the effectiveness of the medicine. Clinical adjustment may include adding other medications or adding or changing the psychosocial interventions, such as behavioral, cognitive or supportive psychotherapy, coaching, and tutoring.
Improving functioning and quality of life
While improvement of the core symptoms of ADHD is important and crucial, it is often not the only goal of treatment. Rather, improved functioning in the real world (being self-sufficient, having a better quality of life and being able to cope with the demands of daily life) may be the most important outcome for an adult with ADHD. Controlled medication studies in adults with ADHD have begun to track and measure these functional improvements including psychosocial and quality of life functioning. Future controlled, long-term medication studies in adults with ADHD are needed to accurately measure the effect of medication on functioning in the workplace, college and interpersonal relationships.
Medication therapy in adults with ADHD and co-existing psychiatric disorders
Approximately two-thirds to three-quarters of adults with ADHD will have at least one other psychiatric disorder during their lifetime. These other disorders include antisocial personality disorder, anxiety disorders, depressive disorders, bipolar disorder, and substance use disorders (SUD). After diagnoses have been made, the clinician and adult should decide which diagnoses need to be treated and in what order.
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.
Discuss the specifics of any medication with your physician or medical professional. New medications for the treatment of ADHD continue to be formulated and researched every day. Similarly, researchers continue to explore the use and effectiveness in the treatment of ADHD of medications that were used previously to treat other conditions.