All of us know that being pudgy or husky can affect a child’s self-esteem, but it wasn’t until we saw a segment that John Stossel did several years ago for ABC’s 20/20, that we realized just how awful children feel about being overweight. John Stossel sat down with a class of kids in late elementary school (if we remember this correctly) and talked with them about being a “fat kid.” At some point in the conversation, he asked them if they had a choice of being fat or of having one arm, which would they choose? His shock mirrored ours when—to a child—they opted to have one arm. Despite his cogent argument that you could always lose weight but you could never regain the arm, he was unable to budge them on their decisions.
So, understanding this, imagine a child who has to deal with rapid mood swings, irritability, anxiety, rage, perhaps learning disabilities (we shall talk about new findings in this area in a future newsletter), and psychosis, and is now being turned into a rather “rubbery” kid by many of the medications used to treat all of the just-mentioned symptoms.
Doctors and parents should do everything to lessen this burden on the child. If a child is on the hefty side, a mood stabilizer that is known not to cause weight gain might be tried first. Depakote and lithium tend to cause weight-gain in youngsters (not all, however) and Trileptal (oxcarbazepine) and Tegretol (carbamazepine) seem to cause less weight gain. Topamax (topiramate) is an add-on mood stabilizer that actually causes weight loss, but at higher levels it can cause a cognitive dulling, and it is not often used as a monotherapy.
The atypical antipsychotics cause by far the most weight gain and Clozaril (clozapine) and Zyprexa (olanzapine) are the worst offenders. Risperdal (risperidone) causes less weight gain than Clozaril and Zyprexa, but still adds some very unwanted pounds; and Seroquel (quetiapine) seems to be intermediate in risk between Risperdal and other antipsychotic durgs. The new atypical, Geodon (ziprasidone) seems to be weight-neutral.
High hopes were pinned on Geodon because of it lack of weight-gain, but we have heard of quite a few cases of an over-arousal syndrome caused by Geodon, perhaps due to its SSRI-like activity. The jury is still out, but it has not proven to be a great boon for children with bipolar disorder as of this writing.
The atypical antipsychotic medications are increasingly prescribed for children with bipolar disorder because they target some symptoms that the mood stabilizers do not. The atypicals may be of particular benefit to children who have prolonged rage attacks, mixed-irritable moods, psychotic symptoms, and possibly very rapid cycling of mood. They also reduce anxiety and agitation, and since children with bipolar disorder cycle so rapidly and often become caught in mixed states where anxiety and agitation are dominant symptoms, the atypicals can be especially effective.
In fact, the atypicals (with their reduced risk of movement disorders) are even being used as a monotherapy for mood stabilization (this discussion can be reviewed in our Fall 2000 newsletter).
The Medical Implications
In our newsletter of Fall, 2000, we first sounded some concerns about a series of general medical, metabolic problems that were being increasingly reported in association with some of the new atypical antipsychotic medications. These include new-onset, type II (non-insulin dependent) diabetes mellitus, changes in lipid metabolism and blood concentrations, sometimes severe and persistent elevation of prolactin and other hormonal imbalances (milk oozes from children’s nipples) and a range of adverse cardiovascular effects that include low blood pressure and abnormal functioning of the heart. The long-term implications of such adverse effects are not known, particularly for youngsters that may need to remain on such medication for decades to come.
In recent months, more stories of emerging problems in the area of glucose metabolism and the development of type II diabetes have begun circulating in the clinical community.
Diabetes: Type I and Type II
Diabetes is a disease that affects the body’s ability to absorb and break down sugars. When a person is diabetic, either the body does not produce or does not properly utilize insulin (the hormone that allows glucose to enter the body’s cells and fuel them).
Type I diabetes mellitus is usually an autoimmune disease and is characterized by almost total loss of beta-cell insulin secretory function in the pancreas. The beta-cells are selectively destroyed. This type of diabetes is often referred to as juvenile-onset diabetes and requires daily insulin injections for life to be sustained.
Type II diabetes mellitus used to be called adult-onset diabetes, and is associated with a decreased sensitivity to the actions of insulin (insulin resistance), along with a variable and usually progressive defect in beta-cell function leading to a relative insulin deficiency.
The emergence of type II diabetes is highly correlated with weight-gain that often accompanies decreased physical activity. The risk for this kind of diabetes is increased by approximately two-fold in mildly obese people, and ten-fold in the more seriously obese. There is an increase of about 4.5% in risk for type II diabetes mellitus for every kilogram (2.2 pounds) increase in body weight.
Symptoms of type II diabetes are excessive thirst, excessive urination, extreme hunger, increased fatigue, irritability, blurry vision or unexplained weight loss (not usually seen when an atypical antipsychotic drug is in the picture). Since almost all of these symptoms can be side effects of psychiatric medications, a parent would be hard-pressed to know if a problem were developing. Often there are more subtle changes in the glucose levels and an emerging case of diabetes is not apparent for some time.
Why Do Atypicals Cause Weight Gain?
We once talked with a mother whose son gained two pounds a day on Zyprexa and continued at that pace until the doctor removed him from the medication. Why would some of the atypicals cause such remarkable weight gain? While it is not really understood completely, one theory postulates that the degree of weight gain is correlated with the drug’s affinity for histamine (H-1) receptors. Zyprexa and Clozaril have a greater affinity for H-1 receptors than do Risperdal and Seroquel. These drugs also seem to have synergistic effects on the H-1 receptors and certain serotonergic receptors, and thus cause more weight gain than other medications.
How Can Weight Gain Be Counteracted? Axid and Other Strategies
Medications with a high affinity for histamine H-1 receptors in the brain typically cause sedation and weight gain. Other medications that antagonize or block histamine H-2 receptors (those that control production of stomach acid) appear to attenuate weight-gain in some persons.
Pharmaceutical companies understand that medications that cause weight-gain are not medications that are going to be prescribed or taken, and they are looking for ways to counter any increasing poundage. Eli Lily, the pharmaceutical company that makes Zyprexa, also manufactures and has underwritten studies on a drug called Axid (nizatidine). It is a histamine H-2 blocking agent, as is Tagamet (cimetidine).
Breir and colleagues designed a well-thought-out double-blind, placebo-controlled trial of Axid for schizophrenic patients that involved132 patients taking 5 to 20 mg of Zyprexa a day. They were divided randomly into three groups: one received 150 mg of adjunctive Axid, twice a day; another group received 300 mg of Axid twice a day; and the third received a placebo with their Zyprexa. The study lasted for 16 weeks.
By week 16, the placebo-adjunct group had gained the most weight (an average of 5.51 kg, or 12.1 pounds). The patients assigned to 150 mg twice-a-day dosing gained an average of 4.41 kg (9.7 pounds); and the group assigned to the 300 twice-a-day dosing, gained the least amount of weight (2.76 kg, or 6.1 pounds). Moreover, with the higher dose of Axid, weight gain appeared to plateau by week eight.
So the patients given the higher dose of Axid still gained weight, but 77% less than if they hadn’t been given Axid at all, and 37% less than the group taking the lower daily dose of Axid.
Some psychiatrists experienced with the use of Axid have found that it must be used at the start of treatment with an atypical antipsychotic agent in order to be effective. One clinician we spoke with, child psychiatrist Lynne Brody of the Weil Cornell Medical Center in Westchester, New York, told us she has used Axid with a number of patients. She reported the following results: one eleven-year-old girl with bipolar disorder became hypomanic; one teenager returned to her normal weight on Axid as it seemed to reduce her appetite; and the remaining patients discontinued Axid because it seemed to make no difference.
No other physicians we interviewed have had great success using Axid to countering weight-gain, nor have we heard reports about the usefulness of another histamine H-2-blocker, Tagamet (cimetidine), which also blocks secretion of acid from the stomach and is said to reduce hunger.
Dr. Brody held out hope for a number of strategies that she institutes when she places a child on a potentially weight-increasing psychiatric drug. Not surprisingly, these involve diet and exercise.
Dr. Brody sits down with the parents alone and discusses her concerns about weight-gain and possible medical complications. If the child begins to gain weight, she encourages a program that will help counter the weight-gain. She wants the child to exercise as much as possible (at least five times a week, for 20–30 minutes at a time) and she sends the family to a nutritionist with a medical background who can individualize a nutritionally sound diet and who can teach the child to make better choices.
Dr. Brody realizes that children with bipolar disorder crave carbohydrates and sugary foods and that this is going to set up continuous fights with an already oppositional child. There will be times a parent may have to relax the rules and let the child indulge, but the life, health, and psychological well-being of the child is at stake, so it’s a fight that is going to have to be fought many times.
Dr. Brody then told us about two bipolar siblings that she sees in her practice. Their father set up a special system for them: they exercise for a reward. He bought an elliptical trainer and some weights. Once his teenage son began to build upper body strength and began to feel much better about his body image, he didn’t need so much rewarding. Dr. Brody reported that his new upper body strength brought about an unexpected bonus: his handwriting actually improved.
Finding an exercise program for a much younger child may be a bit more difficult, but tennis, swimming, and martial arts are activities to think about– perhaps combined with bike riding, walking, or skating. A stationery bike in front of a television means less time driving in cars with drop offs and pick ups. (One should check with the child’s pediatrician before embarking on any exercise program.)
Exercise is a win-win situation because the child typically feels better physically and mentally after exercise. Moreover, exercise consumes calories and promotes leanness, and physical activity plays a major role in glucose metabolism: it lowers blood glucose and improves insulin sensitivity—all counteractions to the development of type II diabetes.
If weight gain gets out of control, a doctor can try switching to another atypical such as Seroquel, or can add Topamax to the medication mix. Topamax can cause weight-loss, sometime an impressive amount. But Topamax often is excessively sedating and can cause cognitive blunting at higher levels. There is a (reportedly slight) risk of glaucoma at higher doses. However, if 50-75 mg of Topamax are taken at night, the drug promotes sleep and fights weight gain for quite a few children.
Medical Tests Needed When A Child or Adolescent Takes An Antipsychotic Medication
One of the original bonuses of the atypical antipsychotics–besides their lower risk of causing tardive dyskinesia– was that they eliminated the need for blood levels and blood tests, a real boon for needle-phobic children and their parents. But as we’ve begun to see the emergence of irregularities in glucose metabolism that these medications can cause, recommendations of frequent testing have to be made.
It is recommended that prior to the institution of treatment with any atypical neuroleptic—particularly if long-term use is contemplated—a set of baseline medical measures be taken. These include measurements of weight, fasting blood glucose, glycosylated alpha-1c hemoglobin (an index of the efficiency of insulin action), and blood lipids. Children should be re-tested periodically (every 4–6 months) during treatment, and those who experience significant weight-gain or have a family history of diabetes should be monitored especially closely. Naturally, a child should be weighed every week and a chart kept so the doctor can assess the situation carefully.
Parents and physicians need to be vigilant about the potential complications of any medication a child is taking, and we’re sorry that the atypical antipschotics carry more of a potential shadow than originally thought. However, they are miracle drugs in many ways: they are life saving, they protect a child from the horrific fate of psychosis and unchecked rage or agitation, and in many cases, they allow a child a chance to grow up normally. And they often allow a family to be just that—a family.
In addition, the atypical antipsychotic drugs can significantly improve many aspects of cognitive functioning, including executive functions, verbal fluency, attention, memory and learning. It is becoming increasingly apparent that many children with bipolar disorder have particular difficulties in the areas of executive function: planning, strategizing, organizing, relinquishing a task and changing set, and other related mental skills.
The cognition-improving benefits of the atypical antipsychotics, as well as all the benefits mentioned above, make the fight against weight-gain worth mounting. Naturally, we hope for better medications that have lesser complications. But for now, the available atypical antipsychotic drugs are the best we have, and with knowledge aobut them comes protection from their adverse effects.
We’ll write again soon.
As always, we look forward to hearing from you and send you and your children our very best,
Janice Papolos and Demitri F. Papolos, M.D.
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The authors would like to thank Catherine Schwartz, Lynne Brody, M.D., Richard Hauger, M.D., and Ross J. Baldessarini, M.D. for their assistance in preparing this article.