It had long appeared that the medication situation for AD/HD was reversed from that of other psychiatric conditions. For other conditions, psychiatrists who treated children and adolescents had relatively fewer medications that had actually been tested on children. We had to extrapolate from adult data, make do with fewer medications, and base our prescribing practices on less research data. Child psychopharmacology seemed like the stepchild of adult psychopharmacology. The exception was AD/HD. This was the condition child psychiatrists could call their own. Although medication choices were still more limited than they are today, clinicians still had more information on how the medications affected AD/HD children than they did on how the same medications affected adults. The tables were turned. The adults were the ones with less data and fewer medication options. It used to be quite controversial to give stimulant medication to older adolescents, let alone adults. However, some adults did get stimulant medication for AD/HD. Usually it involved adolescents who simply continued treatment after they turned 18. Second opinions or special permission from the Drug Enforcement Agency were necessary if one wanted to prescribe stimulants to an adult with AD/HD. Tricyclic antidepressants could be a less controversial choice.
Over the past 20 years, it has become easier and much less controversial to diagnose and treat adult AD/HD. Medication options have expanded, but stimulant medications, usually methylphenidate (Ritalin) and dextroamphetamine compounds (Dextrostat, Dexedrine Spansules and Adderall) are still a frequent starting place in the pharmacological treatment of AD/HD.
Adults and children may have different medical considerations:
Although there is still more information on pediatric AD/HD, there is an emerging body of knowledge specific to medication for adult AD/HD. Many of the medications are the same as those used for children and adolescents. However, when treating adults, there are several general differences to consider. Although adults are generally larger, their liver and kidney function may not be as robust as children. Thus an adult may need less of a particular medication per pound of body weight. A given dose of medication may hang around longer in the adult’s system.
Adults are more likely to be taking medications for other medical conditions such as high blood pressure or diabetes. These may interact with the AD/HD medication. Conversely, some of these other medications may cause inattention and thus exacerbate or mimic AD/HD. For example, a clinician from another state referred me a patient with possible AD/HD. It turned out that an anxiety disorder, along with two medications she was taking, caused her inattention.
Stimulants can cause modest increases in blood pressure and heart rate. Thus there has been some concern that widespread use of stimulant medications in adults might lead to an increase in heart attacks, strokes and other cardiovascular problems.
Stimulants may cause increases in blood pressure or pulse. This is usually not significant at normal doses in most people. However occasionally, the blood pressure effects can be significant. Individuals on very high doses of stimulants or individuals at risk for blood pressure problems should be monitored more closely. Some adults may opt to continue the stimulant and add a blood pressure medication. A small open study suggested that adults who were well controlled on their blood pressure medications could take amphetamine without significant increases in blood pressure. Individuals with blood pressure changes need to discuss the risks and benefits with their physicians.
In late 2011 a large retrospective study of adults aged 25-64 reported that individuals who were taking amphetamine, methylphenidate or atomoxetine did not have a higher incidence of heart attack, stroke or sudden cardiac death than matched individuals who were not taking stimulants. (citation)
Polypharmacy, (prescribing several psychiatric medications at the same time) has become more common. Adult AD/HD by itself often requires more than one medication to control all of the AD/HD symptoms. If the individual has another disorder, such as depression, one may need to medicate this too. I have mixed feelings about the trend towards polypharmacy. When done carefully and systematically, it can bring relief to individuals who have experienced distressing symptoms. However, if done in a rapid or cavalier fashion, it can lead to medical side effects, or it can exacerbate the very symptoms it was meant to treat.
The stimulants, including methylphenidate (Ritalin) and amphetamine (Dexedrine and others) along with some tricyclics (such as Desipramine), have demonstrated efficacy in the treatment of adult and childhood AD/HD. The stimulants have a 60 to 80% response rate. However, some individuals respond partially or not at all. Others develop uncomfortable side effects. Atomoxetine (see below) is a non-stimulant medication approved for the treatment of AD/HD in adults and children. The following is a brief overview of some of the emerging developments in the field.
Food can affect the way stimulants are absorbed. The amphetamines are more likely to be affected. A meal high in fat can slow the absorption of amphetamines. High dose Vitamin C can lower the effect of amphetamines. Grapefruit juice and delay excretion of amphetamines.
Current Second and Third-Line Medications: Alphaagonists, bupropion, (Wellbutrin) and the tricyclic antidepressants. Other medications often used for comorbid disorders or ADHD-related symptoms: SSRIs (eg. Prozac, Zoloft and others) mood stabilizers (Lithium, Depakote, Tegretol) and the atypical antipsychotics. Other than two of the α agonists, these are not FDA approved for the treatment of AD/HD.
Longer Duration Stimulant Medications
Slow Release Methylphenidate
Methylphenidate (Ritalin) is a short-acting drug. It can be difficult to remember several doses per day.
Ritalin SR, one of the older slow-release stimulants, often seems to show inconsistent results. It comes in 20mg pills and cannot be split into smaller fragments. The duration of effects may not always be consistent. Metadate-ER manufactured by Celltech, was released in 10mg and 20mg sizes. Metadate-ER is similar to Ritalin-SR. The active component, methylphenidate, is in a wax-like matrix that releases the drug over time. It lasts about 4-8 hours.
Metadate CD: Released by Celltech in 2001, uses a delivery system called Diffucaps. more recently released which uses a different delivery system. Its peak effect is generally around 5 hours and its effect lasts 8 hours. Metadate CD capsules contain two types of beads. About 30% of the medication is released immediately. The remainder is released over time through beads with a release-control membrane. If the individual cannot swallow the capsule, one can open the capsule and sprinkle the beads on food. The medication has a first peak at about 1.5 hours and a second, larger peak at about 4.5 hours after ingestion.
Ritalin LA: Released in 2002 by Novartis (the makers of brand name Ritalin) this medication is a capsule in which 50% of the beads release the methylphenidate immediately and 50% are released abour four hours later. As compared to Concerta and Metadate CD, this medication gives a stronger earlier dose and relatively less medication in the afternoon. the duration of efficacy is about 6-8 hours.
Concerta (McNeil Pharmaceuticals) is a form of Methylphenidate that uses an osmotic system to deliver methylphenidate in a pulsed pattern. This allows a 12 hour response from a single daily dose. It may prove to be more reliable than Ritalin-SR. Concerta was released in August 2000. The osmotic “oros” system has been used successfully for several years for a diabetes medication and a bladder control medication. With Concerta, the methylphenidate level does not rise as fast as it would with Metadate CD, but the Concerta lasts longer than Metadate CD or Ritalin SR. Drug studies suggest that its duration of action is 12 hours, but I have seen a number of patients who seem to get a shorter duration of effect at all dosage levels. Concerta is now available in a generic form.
Focalin and Focalin XR: Novartis, the manufacturer of brand name Ritalin, has released a non-racemic form of methylphenidate, dexmethylphenidate. Other forms of methylphenidate such as Concerta and Metadate are mixtures of two mirror images (isomers) of the methylphenidate molecule. The body metabolizes the dextro (right handed) form of a compound differently from its mirror image the levo (left handed) form. In the case of methylphenidate, the dextro isomer is the active component and the levo isomer is not significantly active. If you switch from regular methylphenidate to Focalin, you use half as many milligrams. Some individuals feel that Focalin causes less of a problem with appetite but this is not shown consistently in large studies.
Daytrana: Shire released a skin patch form of methylphenidate. The FDA has only approved its use in children and adolescents aged 6-17. It’s commercial release was initially delayed because of FDA safety concerns. After extended testing was done the FDA gave its approval. There are some concerns about skin sensitization from the adhesive. The individual starts to feel the effect of the drug about two hours after applying the patch. One can tailor its duration of action timing the patch removal. I would recommend that adults defer using this medication until there is further testing in other age groups. For more information on this medication, see our article on Daytrana.
Slow Release amphetamines:
Dexedrine Spansules, a long-acting form of d-amphetamine, has been on the market for years. It has a peak effect in 1-4 hours and lasts 6-10 hours. It tends to have a more gradual tapering and thus may have less of a rebound effect. Adderall is a mixture of four salts of d-amphetamine combined with a smaller amount of the less active r-amphetamine. Some clinicians felt that Adderall had a longer duration of action than regular d-amphetamine. However, there are as of yet, no published studies showing that it lasts any longer than short-acting d-amphetamine. Thus we cannot really classify regular Adderall as a long-acting stimulant.
Adderall XR: In 2001, Shire, the manufacturer of Adderall, released Adderall XR. In this formulation, the Adderall is encapsulated in coated beads inside of a capsule. Half of the beads dissolve immediately, and the other half dissolve about 4-6 hours later. There are, as yet, no published studies comparing Adderall XR to the less expensive Dexedrine Spansules. However some patients appear to do better on Adderall XR with its d and r-dextroamphetamine combination. Others do better on Dexedrine Spansules–the all d-amphetamine compound. Adderall XR is now available in a generic form.
Vyvanse: Vyvanse (lisdexamfetamine) is approved for use in individuals age 6 and above. It is also approved for use in adults. The active drug, dextroamphetamine, is bonded to l-lyseine, an amino acid. The drug is not active until it is converted into d-amphetamine in the body. . If one is unable to swallow a pill, one can dissolve it in water and drink it immediately It has a lower abuse potential because it will not produce a rapid onset of action even if it is inhaled or injected. It takes about two hours to show a significant effect after one takes the pill. However one generally still experiences drug effects 14 hours after taking the pill. Because it takes longer to become start working in the morning, some people may take a small dose of short acting dextroamphetamine in the morning along with the Vyvanse.
Non Stimulant Medications
Atomoxetine (Strattera, from Lilly Pharmaceuticals), was approved by the FDA for distribution in November 2002. It became available in US pharmacies in early 2003. Despite its hefty price tag, it is becoming widely used for adults and children with Attention Deficit Hyperactivity Disorder. (AD/HD) It is a non-stimulant medication approved for the treatment of AD/HD in both children and adults. It was the first medication that the FDA specifically approved for the treatment of ADHD in adults. Atomoxetine is a selective norepinephrine reuptake inhibitor. This means that it strengthens the chemical signal between those nerves that use norepinephrine to send messages. Atomoxetine does not appear to affect the dopamine systems as directly as do the stimulants. It is most commonly administered once a day. Those who have trouble with gastrointestinal upset, can take a smaller dose twice a day. Common side effects are headache, abdominal pain, nausea, vomiting, weight loss anxiety, sleepiness and insomnia. It can also interfere with sexual performance in adults. It appears to cause less insomnia and appetite suppression than methylphenidate. However it may cause a higher incidence of sleepiness and vomiting than methylphenidate. The clinical effect appears to last all day and even into the next morning. I sometimes prescribe it twice a day to minimize the nausea. It can be quite helpful to those who cannot tolerate stimulants. However, some patients say that it does not give as strong an effect as what they get from the stimulants. The effect of the medication is gradual. It may take several weeks to se the full effect of a given dose. See our expanded article on Atomoxetine
Modafinil (Provigil) has been approved for treatment of narcolepsy in adults. It is chemically unrelated to methylphenidate or amphetamine. When compared to methylphenidate and amphetamine, it seems less likely to cause irritability and jitteriness. It appears to act on the frontal cortex and is more selective in its area of action than the traditional stimulants. Cephalon In studies of adults with AD/HD, there was a small, promising study suggesting that it might be effective for adults with ADHD. However a larger study sponsored by Cephalon indicated that Modafinil was no more effective than placebo. Some of their studies suggested a positive effect on children when larger doses are used. In the summer of 2006, the FDA announced that it would not approve Modafinil for children with AD/HD. The FDA felt that the medication did not show significant advantages over existing ADHD medications, and expressed concern about side effects in the higher doses necessary to effectively treat AD/HD. There were reports of two cases of rash. One rash was thought to be Stevens Johnsons Syndrome, a serious issue. However this was not confirmed. Modafinil has been used off-label to treat adults if other treatments are not effective. The effect appears to be less intense. It may be useful if the stimulants cause excessive irritability or jitteriness.
Bupropion SR and XL (Wellbutrin) has been used to treat AD/HD for several years. A recent controlled study showed that it is effective in the treatment of AD/HD symptoms in adults. Its structure is chemically similar to amphetamine, but does not have the same abuse potential. It should not be used in individuals with bulimia or a seizure disorder. In my experience, it is not as powerful as the stimulants, but is useful for individuals who cannot tolerate stimulants or for whom a Schedule II drug is inadvisable. Bupropion is FDA approved for depression and smoking cessation.
Alpha-2A-adrenoceptor agonists: Clonidine (Catapress) and guanfacine (Tenex) have been used in adults for the control of high blood pressure. These medications treat high blood pressure by relaxing the blood vessels and slowing the heart rate. Clonidine and guanfacine are approved in adults for the treatment of high blood pressure but not for the treatment of AD/HD. However clinicians have used these two medications to treat AD/HD in adults and children for many years. This class of medications is particularly useful for those with tics, physical hyperactivity, impulsivity or aggression. Like clonidine, guanfacine can reduce tics for individuals with Tourette Syndrome. Because of its sedating properties, clonidine is sometimes used to help people with AD/HD fall asleep. Since both clonidine and guanfacine can affect blood pressure and heart rate, it is a good idea to monitor blood pressure and get an EKG to check the heart rhythm. Clonidine has a very short duration of action. In order to have an extended effect, one must either take it multiple times per day or use the Catapress TTS patch. The patch is applied to the skin and changed every five days. There are now two medications in this class which have FDA approval for the treatment of AD/HD in children and adolescents. Kapvay, a long acting form of clonidine, is FDA approved for use in children and adolescents. However I have used it successfully in adults as well as children. It is usually given twice a day. Intuniv is a long acting form of guanfacine. It is usually given once a day in the evening. It is approved for children and adolescents. Some have prescribed it for adults although this is an off-label use. Years ago there were a few reports of sudden death in children associated with a stimulant/clonidine combination, but some researchers have questioned whether some of those deaths were truly related to the medication.
Omega 3 Fatty Acids: This has been a controversial issues for a number of years. A recent meta-analysis (compilation of multiple studies) was published in the Journal of the AmericanAcademy of Child and Adolescent Psychiatry. In higher doses, there did seem to be a positive effect on AD/HD symptoms. The effect size was not as dramatic as some of the prescription AD/HD medications. The eicosapentaenoic acid component appeared to be the most effective. When individuals with AD/HD self-medicate with this medication, they usually take too low a dose. At higher doses of omega 3s, side effects are possible. These can include nausea, a fishy smelling breath and the side effects of taking in some extra calories.
Effexor and Effexor-XR (venlafaxine) An open trial (not a controlled study) with adults suggested that it might be helpful for some adults with AD/HD. In an open, 5-week study of children and adolescents with AD/HD, some individuals showed an improvement in behavioral but not cognitive measures. Several experienced worsening of their AD/HD symptoms and 25% could not tolerate the medication due to side effects. It is a good idea to monitor blood pressure since some individuals on Effexor show a rise in blood pressure. Sudden discontinuation of Effexor may lead to nausea and vomiting.
Mood Stabilizers are traditionally used for Bipolar Disorder. (Manic Depressive Disorder) These medications include Lithium and several anticonvulsant (seizure) medications such as Depakote (valproate) Tegretol (carbamazepine) Lamictal (lamotrigine) and others. There is debate among psychiatrists about the percentage of AD/HD individuals who also have Bipolar Disorder. Some see the mood swings as part of the AD/HD. Others see it as a sign of a separate, co-existing mood disorder. In either case, the mood stabilizers may be useful to help modulate irritability and rapid mood shifts. These medications require closer medical monitoring. Blood tests and sometimes an EKG may be required. If an adult appears to have both AD/HD and Bipolar Disorder, one often treats the Bipolar Disorder first and then treats the AD/HD. Individuals with both conditions have a significantly increased incidence of substance abuse. Since illegal drugs can have dangerous interactions with some prescribed medications, drug screens may be advisable.
Estrogen Supplementation Some women report that their AD/HD symptoms worsen in the premenstrual period and during the peri-menopausal years. Low or fluctuating levels of estrogen might lead to depressed mood or a worsening of one’s ADHD. Some women with and without AD/HD have reported improvement in memory and attention span after estrogen supplementation. A women who has hormone-related exacerbation of mood or attention span might benefit from a stimulant, estrogen supplementation, an SSRI or a combination of these medications. Since estrogen affects many systems in the body, each woman should review the risks and benefits with her gynecologist. More systematic research is needed. (See Pat Quinn’s article in Nov/Dec 2000 Attention Magazine. Recent data reported in this spring in JAMA from the WHMS study suggested that estrogen-progesterone supplementation might actually accelerate the progress of memory impairment and dementia in postmenopausal women..
Nicotinic Analogues (Medications that act on some of the same brain receptors as nicotine.) Much of the work on the neurological basis for AD/HD has focused on the regulation of dopamine and noradrenergic neurotransmitters. However, there has been a suggestion that poor regulation of the nicotinic receptors may also be involved. Nicotine enhances dopaminergic neurotransmission. Individuals with AD/HD have an increased rate of cigarette smoking. A small study suggested that a transdermal nicotine patch improved AD/HD symptoms in ADHD adults. Studies may focus on more selective compounds in this category that produce an effect without the negative side effects of nicotine. (selective cholinergic channel activators.)
Pemoline (Cylert) The FDA has recommended that individuals who are still taking this medication be switched over to other treatments. This revised recommendation was made in response to several reported cases of liver failure. It is no longer available in the US.
Stimulant Medications: Duration of Action
|Medication||Frequency||Peak Effect||Duration of Action|
|Dexedrine (d-amphetamine)||2 or 3 times per day||1-3 hours||5 hours|
|Adderall||2 or 3 times per day||1-3 hours||5 hours|
|Dexedrine Spansules||Once in am||1-4 hours||6-9 hours|
|Adderall XR||Once in am||1-4 hours||9 hours|
|Ritalin||3 times per day||1-3 hours||2-4 hours|
|Focalin||2 times per day||1-4 hours||2-5 hours|
|Ritalin SR||1 or 2 times a day||3 hours||5 hours|
|Metadate CD||Once in am||5 hours||8 hours|
|Concerta||Once in am||8 hours||12 hours|
Table adapted from Greenhill, Laurence, “Are New Stimulants Really Better?” AACAP Oct. 2001 Annual Meeting
See our article on Strattera (atomoxetine)
See our article on Daytrana (not FDA approved for adults)
Adults: Habel et al, ADHD Medications and Risk of Serious Cardiovascular Events in Young and Middle-aged JAMA. 2011;306(24):2673-2683.
Bloch and Qawasmi, Omega-3 Fatty Acid Supplementation for the Treatment of Children With Attention-Deficit/Hyperactivity Disorder Symptomatology: Systematic Review and Meta-AnalysisJournal of the American Academy of Child & Adolescent Psychiatry Volume 50, Issue 10 , Pages 991-1000, October 2011
J. F. Auiler et al., Effect of Food on Early Drug Exposure from Extended-Release Stimulants: Results from the Concerta®, Adderall XR™ Food Evaluation (CAFÉ) Study Current Medical Research and Opinion , Informa Healthcare , 2002.