19	Other Medicines ANTIDEPRESSANTS AND ANTIHYPERTENSIVES

Although they are not as effective as the stimulants, several drugs called antidepressants and another antihypertensive drug called clonidine can be of some benefit to those with ADHD. But keep in mind these drugs have not received FDA approval for use in the management of ADHD, and so the FDA-approved drugs discussed in Chapter 18 should always be tried before considering the use of these medications with your child. With the development and government approval of atomoxetine (Strattera) and the safer antihypertensive drug, guanfacine XR (Intuniv; see Chapter 18), for the management of ADHD, there has been a marked decline in the use of antidepressants as well as clonidine for managing ADHD. That is because atomoxetine and guanfacine XR have been studied more extensively and have been found to be safer medications with fewer significant side effects on heart functioning than seems to be the case for the tricyclic antidepressants or clonidine. Therefore, atomoxetine or guanfacine XR should be tried before using a tricyclic antidepressant or clonidine for the management of ADHD symptoms. If your doctor recommends any of these medications, or any other for that matter, be sure to ask the questions listed in the sidebar in Chapter 18.

TRICYCLIC ANTIDEPRESSANTS

The brand names (with generic names in parentheses) of the antidepressant medicines that were used most frequently with ADHD before 2003 are Norpramin or Pertofrane (desipramine), Tofranil (imipramine), Elavil (amitriptyline), and Wellbutrin (bupropion hydrochloride). The first three of these belong to the class of drugs known as tricyclic antidepressants. There are other tricyclic antidepressants as well, such as Pamelor or Aventyl (nortriptyline) and Anafranil (clomipramine), but clinical scientists have not studied their effects on ADHD very well, so they are not discussed here. Because Wellbutrin is very different from the tricyclic antidepressant drugs, I discuss it in a separate section.

Norpramin, Tofranil, and Elavil were all developed primarily to treat depression. However, they have also been used to treat some children with ADHD as well as children with anxiety or panic reactions, some with bed-wetting problems, and others with sleep problems such as night terrors. They are useful when a child with ADHD has not shown a good response to the stimulants or nonstimulants discussed in Chapter 18 or cannot tolerate taking those medications. Like all other drugs that modify behavior, these drugs change behavior by altering the brain’s chemistry in certain locations. We believe that in ADHD they increase the amount of the chemicals norepinephrine and dopamine available for work within the brain, especially the prefrontal area, as do the stimulants. The tricyclic drug most frequently studied for treating ADHD is Norpramin, but it is likely that the other tricyclic antidepressant drugs would produce similar benefits.

Sometimes the changes in behavior related to ADHD can be seen within a few days of starting these medicines, while in other cases it may take several weeks. If the medicines are being recommended to treat depression in a child with ADHD, ask your doctor about more modern antidepressants known as SSRIs (selective serotonin reuptake inhibitors) for this purpose. They are likely to be safer medications, causing fewer problems with heart functioning than may occur with the tricyclic medications. If you and your doctor do finally decide to use a tricyclic drug, several weeks will be needed to judge how well a dose of medicine is working. The dose will be increased or decreased, depending on the results of the first trial, and then a few more weeks will have to pass before the benefits of the new dose are noticed. This means your child may require a considerably longer trial to find out whether a tricyclic will work for her than that needed for the stimulants discussed in Chapter 18.

Studies have found that children with ADHD who are given this type of drug are likely to show mild to moderate improvements in their ability to pay attention and control their impulses. They may also be somewhat less restless or hyperactive. Often the most obvious result is an improvement in mood. The children may seem less irritable or quick to anger, somewhat happier or in better spirits, and less anxious or worried. These drugs are not as effective at changing the symptoms of ADHD as the FDA-approved drugs discussed in Chapter 18, which is yet another reason the approved medications should always be tried first.

Like the stimulants, the tricyclic antidepressants are taken by mouth once or twice a day (mornings and evenings). Unlike the stimulants, they do not wash out of the body very quickly and must build up in the bloodstream over longer periods of time. This means that once a useful level of the drug is reached its effects last throughout the day, but it also means that it can take several weeks to gradually withdraw the child from the medication if necessary. Missing a dose or stopping the medicine abruptly may not be dangerous, but it could cause a headache, stomachache, nausea, or aching muscles. The child could also show some emotional or behavioral reactions, such as crying, sadness, nervousness, and problems with sleeping.

What Are the Side Effects?

Slower Heart Rate

One of the problems with tricyclic antidepressants is that they can slow down the transmission of the electrical signal in the heart, causing problems in the heartbeat or heart rhythm. For this reason, every child who is to be tried on such an antidepressant, such as Norpramin, Tofranil, or Elavil, should first be given an electrocardiogram (EKG or ECG)—an easy test that measures how well the heart is beating. If the test gives any abnormal findings, the child should not be placed on any of these medicines. Also, any family history of sudden cardiac (heart) arrest should be a warning to avoid these medicines in most cases.

In fact, because these medicines can have serious effects on the heart, they must be kept out of reach of children or anyone else who might accidentally take too much of the medicine; an overdose could be fatal.

Seizures

Another problem with these medicines is that they may increase the risk of seizures or convulsions, particularly if the child has a history of seizures, has had a serious head injury, or has had some other serious neurological problem. In such cases, it is probably best not to use these medicines.

Minor Physical Effects

The most common side effects of Norpramin, Tofranil, or Elavil seem to be a feeling of dry mouth, which can be handled by giving a child some sugar-free gum to chew, and constipation, which can be dealt with by using stool softeners or adjusting the diet so it contains more fiber or bulk. Some children may also experience blurred vision or even nearsightedness. Occasionally children have had difficulty getting their flow of urine started when they try to urinate. None of these is a serious problem, and they can all be handled by lowering the dose of the medicine.

Rare Side Effects

Some of the side effects of tricyclic antidepressants are rare but can be very serious. Besides the slowed heart rate and increased risk of seizures already mentioned, some children may have a psychotic reaction in which they have disturbed thinking, highly excessive speech, seriously increased activity level, and even hallucinations. Also at high doses, some children experience mental confusion. Where any of these side effects occur, the child’s physician should be informed immediately and the medication discontinued under the physician’s guidance. Increases in blood pressure can occur, although they are mild, and can be of concern if the child already has a history of high blood pressure.

Also rare but not as serious are the occasional cases of rash that have been reported. These are probably the result of an allergic reaction to the food coloring (tartrazine) used in making the pills, and not to the medicine itself. Changing to a different form of the medicine that does not contain the food coloring can solve this problem. Very rarely, children taking these medicines may show some nervous tics. If this occurs to a significant or frequent degree, the medicines can be stopped, and the tic reactions will usually go away. The drugs can also increase the sensitivity of the skin to sunlight, requiring that a child wear strong sunscreen more often or better protective clothing than normal when active outdoors.

Drug Interactions

Because these medicines can interact with a number of other medicines in undesirable ways, it is best to ask your physician which medicines should be avoided while a child is taking Norpramin, Tofranil, and Elavil.

How Are These Drugs Used with Children?

The best doses of Norpramin, Tofranil, and Elavil are 1–5 mg for each kilogram (about 2.2 pounds) of body weight per day. For instance, if your child weighs 80 pounds (38 kg), the lowest probable dose for this child would be 38 mg and the highest 190 mg. Some children may respond well between 1 and 3 mg/kg (between 38 and 117 mg in the example), whereas others will need more medicine to receive any benefit from the drugs. Sometimes, when a child is taking these medicines for the treatment of depression, blood tests may be necessary to see if enough medicine is getting into the bloodstream to benefit the child. This is usually done when the dose seems adequate but the child either is not responding or is showing signs of having too much medication. Even then, however, it is not clear from research that knowing the blood level of the medicine is of much help in determining the best dose.

Unlike with the stimulants, children can build up a tolerance to the tricyclic antidepressants, so typically they cannot take these medicines for more than a year or two. Sometimes these antidepressants begin to lose their effectiveness after only 4–6 months. In these cases, the medicine may have to be stopped for a few months before it can be tried again.

WELLBUTRIN (BUPROPION HYDROCHLORIDE)

Wellbutrin is a relatively new type of antidepressant medication that has been found in several studies to be of some benefit in the management of ADHD symptoms in both children and adults. It is not chemically related to the tricyclics or other types of antidepressants and so does not share the same risks or side effects that were noted above, especially those related to heart functioning. Like other antidepressants, however, the medication does require several days to several weeks to build up in the bloodstream before its effectiveness can be judged. The drug is available in both its regular form and a long-acting preparation. It is typically prescribed so as to be taken several times during each day. There is a very slight risk that the drug may induce seizures, particularly at high doses and more likely in children with a prior history of seizures. Other side effects of the medication include edema (swelling), skin rashes, irritability, loss of appetite, and difficulty falling asleep. Typical doses range from 3 to 6 mg/kg per day, or about 140–280 mg for a 100-pound child.

Didn’t I Hear Something about Antidepressants Possibly Causing Suicide?

Yes, you more than likely have heard in the media questions being raised about whether antidepressant medicines like the tricyclic antidepressants, the SSRIs (selective serotonin reuptake inhibitors like Prozac), and Wellbutrin might increase suicidal thinking or even suicide attempts in children and teens taking these medications. Parents should understand that the evidence here is not as clear as the sensational stories in the media sometimes portray it to be. Typically, these sorts of problems have been reported occasionally in children who are being treated for depression with the medicines. Those children and teens already would have a higher than normal likelihood of having suicidal thoughts or of making suicide attempts given their depression. In an examination of the records of patients with depression or mood disorders who had been treated across seven different studies of these medications, Dr. Bridge and colleagues found the risk for suicidal thinking was 0.7% higher than in children taking placebo in these studies. No completed suicides occurred in these trials. Nevertheless, on October 15, 2004, the FDA issued a public health advisory to warn physicians prescribing these medicines about a potential for increased suicidal thoughts or actual attempts in children being treated for depression with these medicines. If your child is taking one of these medications or any other medication not discussed in this book, see Dr. Timothy E. Wilens’s Straight Talk about Psychiatric Medications for Kids, which offers more information on the FDA warning and the surrounding controversy and advises parents on appropriate precautions to take to protect children and teenagers being treated with these medications.

CLONIDINE

Another type of medicine shown to have some benefit for children with ADHD is clonidine, a drug frequently used to treat high blood pressure in adults. (Clonidine is marketed under the trade name Catapres by one drug company, but it is usually sold and referred to by its generic name.) Clonidine is similar to guanfacine XR (Intuniv), the antihypertensive drug discussed in the preceding chapter that has received FDA approval for use in treating children with ADHD. The fact that both drugs can produce changes in behavior and mood make them of some benefit to children with ADHD who have problems with or get no beneficial effects from the stimulants or with atomoxetine. These two antihypertensive drugs differ in that guanfacine produces much less adverse effects on heart functioning and blood pressure than does clonidine and so carries less risk for side effects (fainting, dizziness, nausea) that may be related to them. Guanfacine XR is also sustained longer in the bloodstream and so requires fewer doses during the day, as the XR in its name implies (XR = extended release). For these reasons, if an antihypertensive drug is to be considered for use with a child with ADHD, then guanfacine XR would be the preferred choice over clonidine. Other disorders for which clonidine has been used include migraine headaches, schizophrenia, bipolar disorders, obsessive–compulsive disorder, panic disorder, and serious eating disorders like anorexia nervosa. It has also been used in treating the tics, vocal noises, and other involuntary movements seen in Tourette syndrome.

When used for children with ADHD, clonidine may reduce the motor hyperactivity and impulsiveness seen with the disorder. It may also increase a child’s cooperativeness with tasks and directions and increase the child’s tolerance for frustration. Dr. Robert Hunt of Vanderbilt University, a nationally recognized expert on the use of this drug with children with ADHD, reports that clonidine may not be as effective as the stimulants in improving such a child’s sustained attention or reducing distractibility. However, it may be as effective as the stimulants in reducing aggressive and impulsive behavior or the tendency to become overaroused very quickly. Dr. Hunt believes that this medication may be best suited for those children with ADHD who are very oppositional or defiant or who have conduct disorder.

When taken by mouth, clonidine may produce changes in behavior that can be noted within 30–60 minutes and may last for 3–6 hours. It also comes in an adhesive patch that can be worn on the skin. When this skin patch is used, changes in behavior may not be noticed for several days. However, it usually takes several months before one can tell just how much benefit the drug is producing in the management of a child’s behavioral or emotional problems.

What Are the Side Effects?

The most common problem children have with clonidine is sedation or a feeling of tiredness or sleepiness. This can last as long as the first 2–4 weeks after a child begins the medicine. During this period the child may take frequent catnaps, especially during boring activities. In some children, perhaps 15%, this sleepiness or fatigue may last longer and be troublesome enough to warrant stopping the medicine.

There may be a mild drop in your child’s blood pressure after starting this medication, but this is rarely significant. There may also be a slight decrease in heart rate, but again this is rarely serious. Headaches or dizziness may be noted in some children, again typically within the first 4 weeks of starting the medicine. Some children have complained of nausea, stomachaches, and even vomiting, but these are also usually limited to the first few weeks of starting the medicine. Constipation and dryness of the mouth may also be seen in some children. Much less likely to occur are depression, erratic changes in heartbeat or rhythm, nightmares or disrupted sleep, increased appetite, or increases or decreases in weight. Rarely, problems with increased anxiety, a sensation of coldness in the fingers or toes (known as Raynaud syndrome), or water retention may be seen.

The medicine should never be stopped abruptly. If it is, a child may experience a rapid rise in blood pressure, show agitation, and/or become anxious; complain of chest pain or fast and irregular heartbeat; and develop headaches, stomachaches, nausea, or sleep problems.

Clonidine can also interact with other drugs to create problems for a child, so you should advise your physician of any medication a child is on before clonidine is prescribed, or of any new medications being considered for the child while clonidine is being taken.

How Is Clonidine Used with Children?

Before starting this medicine, your physician may want to conduct a complete physical examination of your child, including an EKG and some blood work. Dr. Hunt recommends that children with ADHD be placed on doses of 0.15–0.30 mg/day. The drug is usually begun at much lower doses (0.05 mg given at night). The dose is then gradually increased every few days or less often by adding doses of 0.05 mg given at different times of the day until a child is taking this dose four times a day. At this time it may be necessary to increase the dose from 0.5 to 1.0 mg for one of the four doses each day. These increases can continue until some benefit has been noticed from the medicine or the side effects become a problem for the child. The drug is usually taken orally three to four times a day (commonly at mealtimes and bedtime). Although some improvement in behavior may be seen in the first 2–4 weeks, it can usually take 2–4 months before the full benefit of the medicine is noticed.

A skin patch of clonidine, named Catapres-TTS, is available. It is worn like an adhesive bandage and should be placed on a clean, relatively hairless patch of skin out of easy reach of the child’s hands (usually the lower back or over the back of the hips). Each patch can be worn for about 5 days. Children can take baths or showers with the patch on, but after swimming or heavy sweating the patch may need to be replaced. Dr. Hunt recommends that children be started on oral clonidine until the proper dose is determined. They can then be switched to the skin patch, which avoids the problems of taking oral medication at school, if desired.

Any child taking clonidine should be followed by the physician weekly while the different doses are being tried, and then every 4–6 weeks once a stable dose has been reached. Blood pressure, heart rate, and growth should be monitored at these regular visits.

If your physician is not familiar with clonidine or you would like to read more about it yourself, you may wish to consult Straight Talk about Psychiatric Medications for Kids by Dr. Timothy E. Wilens (see “Suggested Reading and Videos” at the end of this book).