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My son, 24 years old, was just diagnosed with paranoid schizophrenia 2 weeks ago. He was placed initially on Zyprexa 10 mg QD and it was increased to 20 mg. He continues to proclaim his lack of need for any medication and becomes very angry with me when I try to explain his illness to him. I try to relate it to to any physical illness needing daily medication -- i.e. diabetes, hypothyroidism, etc What is the best route to take for a mother to therapeutically support and talk with her son without invoking his misplaced anger?

Susan Hice
Lakeland, Florida

Answered by Robert Whitaker:
I think this is an extremely important question because it raises the issue of how we, as a society, talk about schizophrenia, and whether parents and patients alike are being given candid information. I do not believe they are, and I also believe that we need such candor so that any discussion of taking meds is well informed. Specifically, I think the following is important to consider:

a) We do not know the causes of schizophrenia.

We often hear that drug treatments for schizophrenia are like insulin for diabetes. Unfortunately, this is a misleading metaphor. With diabetes, the biological deficiency is well understood, and insulin is indeed a specific remedy for the illness -- the drug supplies what is lacking in the body. But we have no such knowledge about the underlying biology of schizophrenia. In fact, there may be any number of causes. It may also be that some people so diagnosed have no underlying biological problem, and that environmental triggers (extreme stress, etc.) have caused the schizophrenic break. And the key point for the purposes of this discussion is that without this knowledge, we can't say that the drugs used to treat schizophrenia are like "insulin for diabetes." The drugs do not fix any known biological abnormality.

b) What the drugs do.

We also often hear that antipsychotic drugs "balance" the patient's brain chemistry. This is not true. What the drugs do is block neurotransmitter activity in the brain. For example, it is well established that standard neuroleptics powerfully block receptors for dopamine, which is one of the brain's primary chemical messengers. Olanzapine, the drug mentioned in this question, blocks both dopamine and serotonin receptors. It also blocks adrenergic, cholinergic, and histaminergic receptors. Now blocking these receptors may dim, or even extinguish, certain symptoms of schizophrenia, like hearing voices, but they may also cause a wide range of adverse effects. In the clinical trials of olanzapine, weight gain and sedation were common problems, and there were any number of other side effects reported as well. There is concern that olanzapine raises the risk of diabetes as well. But these adverse effects are not unexpected. Rather they are an expected consequence of blocking the receptors for these various chemical messengers in the brain.

c) Why patients may not like taking the drugs.

People taking antipsychotic medications have widely varying reactions. Some may respond well. But others may find the drugs objectionable for very understandable reasons. For example, they may not like the fact that the drugs make them feel sedated. Or they may complain that the drugs make them feel lethargic. Or emotionally empty. They may also find that the drugs slow their motor movements. Thus, I think it's unfortunate to simply say -- as we often do at a societal level -- that people with schizophrenia resist taking the drugs because they don't know they're ill. In fact, people placed on these drugs may have very rational motives for not wanting to take them, and that is that they don't like how the drugs make them feel (which in turn is related to the fact that the drugs block neurotransmitter activity in the brain).

d) Do the drugs lead to good long-term outcomes?

The other question that should perhaps inform this conversation is this: Do we have reason to be confident that constant medication leads to good long-term outcomes? This is a contentious issue, but here is just one of many curious facts that can be found in the medical literature: The World Health Organization has twice found that outcomes for people with schizophrenia are much better in the poor countries of the world, like India, Nigeria and Colombia, than in the U.S. and other "developed" countries. And in those poor countries, the WHO reported, only 16% of patients are routinely maintained on antipsychotic medications. At the very least, that is the sort of fact that raises some degree of doubt about whether the drugs promote long-term recovery.

In sum, I believe that this issue of "medicating schizophrenia" is much more complicated than what parents and patients have typically been led to believe, and that a more candid, complete view of the disorder and our treatments for it should inform discussions of this type.

Robert Whitaker

Answered by John Hsiao, M.D.:
I would like to comment on Ms. Hice's question about her son and on Mr. Whitaker's answer. Obviously, as a physician working on psychiatric research at NIMH, my outlook and opinions about schizophrenia and how best to treat it differ considerably from Mr. Whitaker's. What I think we would agree on, however, is that schizophrenia is a devastating illness: its symptoms (hallucinations and delusions) are terrifying; having the illness can destroy a young person's life; and family members, particularly parents, who must witness this deterioration often feel powerless and suffer terribly, themselves. Mr. Whitaker and I would also agree on many of the facts about schizophrenia and antipsychotic drugs provided in his answer to Ms. Hice. We do not know exactly what causes schizophrenia. The analogies to diabetes or to "balancing brain chemistry" are sometimes useful simplifications trying to explain a brain disease we don't fully understand. All the antipsychotic drugs have side effects, which in some people, can be really terrible. Treatment with antipsychotic drugs does not guarantee a good long-term outcome, and many people with schizophrenia remain quite disabled socially and vocationally. We need far more research to inform our efforts to help people with schizophrenia and their families.

I take all this as a challenge: we need to improve our understanding of what causes schizophrenia, we need to find better treatments, and as President Bush indicated in his address from New Mexico yesterday, we need to improve and better coordinate our systems for mental health care. Mr. Whitaker (as I understand him) takes our need for continued scientific research and better service integration as an indictment: psychiatry, the pharmaceutical industry, government, and society as a whole have failed people with schizophrenia. So is the glass half full or half empty?

Maybe one of the reasons Mr. Whitaker and I differ in our outlook is that, as a physician, when I see people with schizophrenia and talk with their family members, I have a hard time telling them that the glass is half empty. I tell patients and families that in most instances drug treatment can control of many of the illness' symptoms. I indicate that all drugs have side effects, but that we can often work to minimize them by adjusting the dose, changing drugs, or adding another drug. I tell my patients that this is generally a long-term illness and while they may need to take medications for the rest of their lives, only time will tell. I emphasize that future efforts to reduce medication should be carefully conducted with the monitoring of a physician. I explain that maintaining supportive social relationships, participating in personally meaningful planned activities ranging from rehabilitation to school or work, and avoiding substance abuse are also important elements of illness management and recovery. I am willing to bet that nearly every psychiatrist in America tells his or her patients something similar .

Scientific and theoretical questions aside, many family members of persons with schizophrenia face the same dilemma articulated by Ms. Hice. In the short term, scientific data is clear: following an episode of schizophrenia, medication adherence is a major determinant of outcome: approximately 70% of patients who discontinue medications will experience a relapse and rehospitalization; this figure is reduced to approximately 30% if medications are maintained. Following a first episode of illness it is particularly important to try to avoid a second episode. Studies indicate that the longer medication treatment is delayed, the longer it may take for medicines to reduce symptom severity.

The general goal of medication treatment is to determine the most effective particular medication with the least side effects for the individual patient and over time determine the lowest possible dose of that medication required to prevent recurrence of symptoms. A patient's psychiatrist should be prepared to carefully explore medication side effects, make changes to minimize side effects, and experiment to find a regimen that is acceptable to the patient.

So, to answer Ms. Hice: Yours is a very difficult and painful situation. You have quite enough responsibility and burden already, in taking care of your son, and you shouldn't have to be his therapist and psychiatrist, as well. It's not your job to explain what schizophrenia is or why he should take his medicines. While your support is important, in the end, your son will have to take responsibility for his illness and its treatment.

It would probably be useful for you to talk with your son's psychiatrist and/or therapist (with his permission, of course), asking them questions and telling them what's going on at home. You may also want to contact your local chapter of the Alliance for the Mentally Ill and talk with people there. There are a lot of parents who have gone through what you're going through now and who may be able to advise you on how to handle things. Most of all, you should take care of yourself, and try to make sure that your son's illness doesn't take over your life, as well as his.

John Hsiao, M.D.

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