I hope it is now clear to you that there are several components that are essential in the treatment of the patient who has been diagnosed with ADD. Medication is only one such component. Several types of medication are used in the treatment of adult ADD. Before prescribing any medication, it is critical that the psychiatrist has considered the possible presence of comorbid conditions. I refer the visitor to Dr. Goodman’s article on the possible consequences of prescribing a stimulant medication to a patient with ADD who also has a bipolar illness, without first managing the patient with a mood stabilizing medication.

    Stimulants are the medications most commonly prescribed for patients with ADD. The term stimulants refer to a class of medications that increase in dopamine and norepinephrine in the brain.  These are the neurotransmitters presumed to ameliorate ADHD symptoms. Stimulants fall into several categories.

1) Methylphenidate-there are numerous preparations of the compound (Ritalin, Concerta, Metadate, Methylin, Focalin, generic). The compound in each preparation is the same, however the method of release is different.  The vehicle of release, as it's called, determines the duration of action. For example, a single dose of generic methylphenidate lasts 2-4 hours, whereas Concerta, the longest acting, is effective up to 12 hours, perhaps longer. For someone who can't remember, single daily dosing increases medication compliance and adds convenience. There is a longer-acting sustained released form of Ritalin which many clinicians find less reliably consistent in its effectiveness than the immediate release form. Some patients observe that generic methylphenidate is less potent, milligram per milligram, than brand name Ritalin. The other agents have varying durations of action.

2) Amphetamines- there are several compounds and preparations of the compounds. Adderall is a mix of four amphetamine salts. The generic form last up to 6-7 hours. Adderall XR has duration of action up to 12 hours, longer is some people.  The XR form is composed of micro-beads. Half the micro-beads are released immediately while the second half are released approximately four hours later accounting for the extended duration of action.  Again, single daily dosing increases medication compliance and adds convenience. Dextroamphetamine (Dexedrine), one of the amphetamine salts, is available as a single agent.  It's available in a short acting (3 hours) or longer acting (6 hours). Methamphetamine, a sustained release form (Desoxyn), known for its high abuse potential, is rarely used.  However, there is a rare patient who reports significant improvement with this agent beyond the other stimulants.  All of the previous stimulants are classified as Category II, meaning there is abuse potential. For physicians, it means that refills can not be written or called into a pharmacy.  Each prescription needs to be hand-written.

3) Pemoline-the only prescription stimulant not in Category II is pemoline (Cylert). Because of pemoline's class, it is free of the prescription restrictions. Pemoline is convenient in another way in that it is a once per day drug. Unlike the other stimulants which begin working after the first dose, Cylert takes a few weeks to begin working.  Pemoline is not often used because of potential liver damage in children. Signed consent by patient/parent and frequent blood tests are strongly recommended. The manufacturer no longer recommends it as a first-line drug for ADD. It may be used with less risk in adults. Because it is not abusable and there is no street value, pemoline is a possible choice in adult ADHD patients with recent substance problems or someone in recovery who wishes to avoid abusable medications.

      Side effects of the stimulants as a group include nausea, headaches, tremors, insomnia, loss of appetite and possible worsening of the pre-existing tics. The worsening of tics is now hotly debated in current research.  The presence of tics is not an absolute contraindication for stimulant use.  Blood pressure elevation and increased pulse rate may also be seen.  At our center, we take patient's blood pressure and pulse before starting medication and then periodically after dose changes. We have detected high blood pressure in some patients before we started the stimulant.  This hypertension might have been ascribed to the stimulant if we hadn't detected it before treatment.  On occasion, we have elected to treat stimulant-induced hypertension with and anti-hypertensive medication instead of discontinuing the stimulant.  This is done when the patient reports significant improvement, understands the treatment options and chooses to remain on the stimulant and the antihypertensive agent.

    Stimulants are very effective in calming the restless ADHD patient, improving his or her ability to focus and improving the patient’s ability to inhibit distraction and impulsivity. The initial response to a stimulant may be dramatic, and the patient may need to be persuaded to temper his or her expectations after subsequent dose adjustments.

    Atomoxetine (Strattera), a norepinephrine agent, manufactured by Lilly, is the first medication approved for ADHD in 30 years. In fact, it is now the only medication approved for ADHD in adults.  Initial trials in children were then extended to adolescents and adults. Atomoxetine was renamed from tomoxetine at the request of the FDA because it sounded to similar to tamoxifen, a breast cancer drug.  Given once-daily in the morning, atomoxetine seems to last all day.  In contrast to stimulants that work within 1 hour, atomoxetine may take a week before improvements are noticed.  Dosing in children is weight-based. In adults, PDR recommended starting dose is 40 mg daily then increased to 80 mg 4 days later. However, we suggest starting at 25 mg daily for four days, then to 40 mg daily for 10 days, then to 80 mg daily.  This assumes the patient is on no medication that may inhibit Strattera's metabolism. Because atomoxetine is metabolized by a specific liver enzyme, its dosing may need to be modified when combined with fluoxetine (Prozac), paroxetine (Paxil), or bupropion (Wellbutrin).  If the patient is on such medication, the holding at 40 mg daily for 14 days to assess benefit and side-effects is merited. If no side-effects, then increase to 60 mg daily for two weeks and then on to 80 mg daily, continuing to assess for side-effects. Side effects to look for in adults are insomnia, daytime fatigue, decreased appetite, dry mouth, constipation, erectile dysfunction.  Increases in blood pressure and pulse occur but are not substantial.  There may be an occasional vulnerable adult person for whom this may be an issue. Although atomoxetine increases norepinephrine, trials in Major Depression have not proven its benefit for these symptoms.

    Several antidepressant medications have been found to be helpful in the treatment of ADD. Tricyclic antidepressants, particularly desipramine, have been helpful in both children and adults. Like pemoline, these medications take a few weeks to work. Advantages include single one per day dosing and the ability to call in prescriptions and authorize refills. There is some controversy over the dosing of tricyclic antidepressants for ADD. There are advocates of both low and high daily doses. Unfortunately, there is no reliable correlation between antidepressant blood levels and improvement or ADD symptoms. Side effects of the tricyclic antidepressants can include dry mouth, constipation, increased appetite with possible weight gain, lightheadedness on standing up quickly, and heart rhythm problems in patients with certain types of pre-existing heart disease. Many clinicians report that tricyclic antidepressants are more effective in reducing hyperactivity and distractibility, and less effective than stimulants in reducing impulsivity. These medications are wonderfully effective in reducing anxiety and improving depressed mood in ADD patients. Tricyclic antidepressants effect several neurotransmitters in the brain beyond norepinephrine and dopamine.

    Other antidepressants that have been found to be helpful in the treatment of ADD include bupropion (Wellbutrin SR) and venlafaxine (Effexor XR).  Bupropion is a norepinephrine and dopamine antidepressant. It is generally taken twice per day. It seems to improve both the cognitive symptoms of ADHD and the comorbid mood /anxiety disorders. Its benefit in adult ADHD patients was demonstrated in a double-blind placebo controlled trial. Venlafaxine may be taken as a single daily dose. It is very helpful in reducing comorbid anxiety and depression, although it seems to have little effect on the cognitive symptoms of ADHD. The research with venlafacine has tonly been open-label studies and drop-out rate is higher than other trials. It affects the brain by increasing the availability of serotonin at doses 0-150 mg per day, and serotonin and norepinephrine at doses over 150 mg per day. 

In general, antidepressants are helpful for patients who are unable to tolerate the side effects of stimulants, or as additional agents with stimulants.  Serotonin antidepressants ( Prozac-fluoxetine; Zoloft-sertraline; Paxil-paroxetine; Celexa-citalopram, Lexapro-escitalopram) work by increasing the availability of serotonin.  These agents are very effective at reducing anxiety/agitation, increasing one's "emotional fuse" (decreased emotional reactivity), improving depressed mood and reducing impulsivity.  There are two studies using Prozac in ADHD children.  In one study, Prozac was added to methylphenidate and it was noted that the childrens' mood improved and overall function improved beyond the group of children receiving methylphenidate alone.  In the other study, Prozac was used alone and those children also showed improvement beyond the placebo group.

    In the above adult study bupropion (Wellbutrin SR) was significantly better than placebo. Remember that the antidepressants take time before a benefit is noted.  Patients on these medications need to be patient when evaluating the benefit. 

    Our experience in ADD adults is similar.  It is very common for many of our patients to be on a stimulant for cognitive improvement and an antidepressant for anxiety, mood and impulsivity control.  We have not seen any consistent side-effects with this combination and therefore consider the combination safe.

    Sometimes, mood stabilizers are helpful in the treatment of ADD patients, particularly those who have problems with anger and rage outbursts. Of course, as mentioned above, mood-stabilizers are the first-line medications for patients with comorbid bipolar disorder and ADD.

       There are a number of new medications in development.  The ADHD area is exploding with new research. Several new agents are in Phase II and III clinical trials. Many of the research protocols include adult patients.  The companies understand the need to seek the adult ADHD indication from the FDA.