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.
Other Options
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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in schizophrenia and related disorders: A randomized, controlled, double-blind
study.” Presented at the 41st Annual Meeting of the New Clinical
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Henderson. “Atypical antipsychotic agents and diabetes mellitus.” Primary Psychiatry 2000; 7: 65–68.
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diabetes mellitus in patients treated with atypical antipsychotic agents.” Journal of Clinical Psychiatry 2001; 62 (Suppl 27): 10-14.
Lebovitz, Harold E. “Diagnosis,
Classification, and Pathogenesis of Diabetes Mellitus.” Journal
of Clinical Psychiatry 2001; 62 (Suppl 27): 5–9.
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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.
Copyright 2001
