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Second Line Medications

All of the medications below involve more risk. That is, in rare cases, people can have serious side effects. This means that there is additional monitoring required.

Why do you use these drugs?

Because other drugs have not worked. Except in a few cases (comorbid severe tic disorders, some mood disorders, some substance abuse disorders) the stimulant medications are tried first before considering the drugs below.

Because the risk of ADHD is far greater than the risk of the medication.

ADHD is not always a mild disorder. People with ADHD sometimes engage in very risky behaviors. These are risky to themselves and others. ADHD can totally demoralize a child and put them at significant risk for depression. The risks of things like substance abuse related accidents, motor vehicle accidents, demoralization, other psychiatric disorders and even suicide is not that small. If you look at a group of children with ADHD that go to see a pediatric psychiatrist and then see how they are doing four years later, 51% will have required tutuoring, 34% will have repeated a grade, 15% will be in special classes, and 16% will have been diagnosed with a learning disability. Compared to children without ADHD, they will be 10 times more likely to have manic-depressive disorder, 8 times more likely to have depression, and 4 times more likely to have major anxiety problems. (1) ADHD can be a very serious illness.

The risk of serious problems with the drugs below is on the order of 1 in 10,000 or less. To put that in perspective, your chance of being killed in a car accident on the way to my office is .7 in 10,000. Compared to the risks of ADHD, most people would say the risks of these medications are worth taking.

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Bupropion ( Welbutrin ) Zyban, Amfebutamone

Bupropion has been available in the USA for about 10 years. It is used primarily as an antidepressant. However, it affects the same chemicals in the brain (dopamine and norepinephrine) that other drugs for ADHD effect. As a result, it has been tried in ADHD in children and adults. There are only a few studies of this drug in children. However, all of them have found it to be effective. In the one study which compared it to Ritalin, it was found to be almost, but not quite, as effective as Ritalin. (3) It has been used in children who have Conduct Disorder, Substance abuse problems and Attention Deficit Hyperactivity Disorder and it has been found to be helpful. (15) It comes in a slow release form, which means there is no need for a middle of the day dosage. The average dosage is about 3mg/kg. However, sometime higher doses are used. The drug is available only as a slow release preparation in Canada. It comes in 50, 100, and 150mg sizes. Usually it is given once or twice a day and it is not recommended that any dose be greater than 150mg.

Side effects

Rashes are not uncommon, about one out of 6 children can get one which usually resolves over 3-4 days. Nausea and vomiting can occur. About 1/3 of children will lose a little weight.

Less common side effects include irritability, sleep problems, and head-aches. It can cause seizures. This is most frequent in over doses and when patients also have Bulimia. In adults, 4 out of 1000 people will have a seizure using the short acting form of the drug. However, the long acting form used in Canada only causes seizures in 1 in 1000 people (9). This is about the same as most of the drugs used for depression. Seizures have occurred in children, but usually at higher doses. It is still unknown if the seizure rate in children is lower, higher, or the same as in adults. There are no other long term side effects or risks. On the other hand, it has not been around a long time. Over all, the early data suggests the side effects are slightly less than stimulants, but not a lot less. (4)

Good points about Bupropion
Compared to the other non-stimulant drugs for ADHD, the monitoring necessary is minimal. No ECGs or blood tests are necessary. It can be helpful when depression is also present. It has been used a lot in the USA for ADHD without any major problems. If a child has failed to respond or tolerate the first line drugs and won't have his blood drawn, it is a great choice. (5)

Bad points about Bupropion
There has been some, but not a lot of research on this drug. It seems quite safe in adults, and it probably is in children. However, there is a possibility that something will come up which is a problem with this drug in the future.

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Tricyclics - This is a group of medications (desipramine and nortryptiline) which were the first drugs used for depression in adults. One of them, imipramine or tofranil, has been used for years children who bedwet. They work in a slightly different part of the brain. The good thing is that they work very well in children who are also depressed or anxious. They do not wear off over the day. They can be given it at breakfast and bed time. They do not usually worsen tics. It is my first choice in kids with mild tics and ADHD.

So why aren't they used more?
Approximately 5-10 children have died suddenly while taking one of these drugs, desipramine. This turns out to be a rate of about 8 per million. Children die of unknown causes at a rate of 8 per million. To put this in perspective, the childhood suicide rate is about 8 per million. The risk of dying in an auto accident are about 70 per million. So, although there is a very slight risk, compared to the risks of the disorder, it is very small. In my practice, it would be ten times more likely that someone would die on the way to their appointment with me in a car crash than die of sudden death related to these drugs. There is still a debate as to whether this small increase in deaths is from the medication or something else. It is also unclear as to whether monitoring as below will pick out these super rare cases. It has only happened with desipramine. A much more real risk is over dose. If children or adults take too much of these drugs accidentally or on purpose, they can die. These drugs can cause rhythm problems in the heart, blood pressure problems, and fast pulse, plus constipation and dry mouth and occasionally sweating and dizziness. It is very hard to figure out the dose.

First get an EKG. If it is normal, we start the drug at a very small test dose amount. For Desipramine, this is usually 1 mg/kg. The doses for Nortryptiline are half of this. Over the next few weeks I slowly increase the dose to 3-5 mg/kg for desipramine or 2-3 mg/kg for Nortryptilin . At this point we check a blood level and another EKG. It takes a week to get the result back. Based on the results of the blood test, I adjust the dose, and occasionally a person will need another EKG and blood test, but not usually. I check the blood pressure and pulse after a few weeks. The toxicity of these drugs is mostly related to the blood level and the EKG. By following these very conservative guidelines, the drug is very safe and often very effective.. BUT, it is a fair amount of hassle. Obviously if someone is dead set against having their blood drawn, they will never get this.

I heard of somebody who was taking two drugs at the same time. Why would you ever do that?
Attention Deficit Hyperactivity Disorder is sometimes so severe that one drug won't control it. It can be a life threatening disease as it makes accidents much more likely. There are certain cases where it is necessary to use two drugs to control Attention Deficit Hyperactivity Disorder. This requires even more monitoring and even a more careful approach.. What follows is a table of the medications.

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Medication
Brand name
Usual Dosage
Problems
Advantages

Methylphenidate
Ritalin
Up to 1mg/kg two to three times a day
Need to give at school, remembering to give it
Minimal monitoring

Dexedrine
Dexedrine Spansules
1/2 mg /kg once a day
Possibly slight increase in side effects
Once a day, Minimal monitoring

Dexedrine
Dexedrine Tablets
1/2mg/kg 3-4 times a day
Frequent dosing
Can be helpful when you want to start dexedrine at a very low dose

Tricyclics
Norpramin, Aventyl
1-3 mg/kg
Blood tests, ECGs, Blood Pressure, pulse
Can be helpful if other things have failed

Buproprion
WelbutrinSR
3mg/kg once a day
No long term data
Well tolerated

Clonidine
Catapress, Dixarit
5mcg/kg
ECG, Blood pressure, pulse
Helpful if tics are present

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The bottom line is ...

Drugs can be very beneficial. There is no free lunch; they all have side effects. If used carefully they can be lifesavers, if not, a nightmare.

Alternative medicine treatments

There are quite a number of substances, which are supposed to help ADHD, which are "natural". Usually these are combinations of vitamins, herbs, minerals, and other plant products. They are usually advertised as being very safe and effective. For the most part, they are very safe. There are far less side effects with these agents. On the other hand, there is not the same kind of research data that is found with medical treatments.

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For me to recommend a substance or drug for any disorder, it must meet some tests.

Someone other than the company which makes it must do research on it. I wouldn't believe the Ford dealer about his trucks, and I wouldn't believe the Ritalin sales person about his drug and I wouldn't believe the herbal company about their new herbal treatment for ADHD.

The results should be published in a referenced medical journal. This way I know that reviewers have checked it out first and that the research meets basic criteria for scientific research. "Vitamin Retailer" is not one of those journals.

A double blind placebo trial should be completed. By this I mean that the substance or a placebo is given to a group of children and no one knows until the end of the study who really got the new substance and who got the placebo. This is the most accurate type of study.

At the moment, no alternative treatment meets all these criteria. However, there is one that is relatively close. That is supplements with Omega 3 Fatty Acids in them. This is based on the observation that children who are hyperactive have lower levels of these substances in their blood.(17) These supplements have been used for other purposes in medicine so we have a fairly good idea about their safety. There are no good independent studies of their effectiveness, however. They take a few weeks at least to work.

Based on my experience, they seem to be mildly to moderately effective. They work better on younger than older children and work better on hyperactivity than inattentiveness. Again, this is just based on my observations, not any research.

So when are they reasonable to consider?

When ADHD is only mild. Overall, they do have a lot less side effects than stimulants, and if the problem is not severe or urgent, it is worth considering. When preschoolers have ADHD which requires medical treatment. As mentioned in the preschool section, this age group has more side effects and a poorer response to medical treatments such as stimulants. As a result it is worth trying these agents.

When the ADHD is mild and a child has severe tics. These supplements do not worsen tics. There are a number of sources of Omega 3 Fatty acids. Here in Southwest Nova Scotia, the three most popular are Evening Primrose Oil, Herring oil capsules, and a combination of tuna fish oil, thyme oil and Evening Primrose oil called Efalex. These are available at pharmacies and health food stores. Since each company has its own directions and sizes, the only advise I can give is to follow the instructions.