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Can Psychosis be Prevented?

I recently read an article in Discover magazine entitled “Stop the Madness.” It was about a new treatment program that allegedly can prevent schizophrenia and other forms of psychosis. I found it very disturbing.

The PIER (Portland Identification and Early Referral) program was founded by a psychiatrist, Dr. William McFarlane, in Portland, Maine. It has recently expanded to 4 other US sites and there are similar programs in several other countries. PIER is an effort to find and treat patients in the “early stages of deterioration towards psychosis,” so as to prevent the development of psychotic illnesses like schizophrenia, bipolar disorder, and major depression. The program involves various psychosocial interventions and psychotropic drugs.

On the surface it sounds promising, but there is a dark side. I’m particularly concerned about the use of antipsychotic drugs in people who haven’t been diagnosed as psychotic.

McFarlane’s own website points out that “With treatment, most people make a full recovery from a psychotic episode.” So what’s the rush? Why be so concerned about early identification? Is it reasonable to treat an illness before it’s diagnosed?

McFarlane thinks that a first psychotic episode should be prevented if possible because it might have lingering effects on the brain that would interfere with recovery. He is also concerned that a psychotic episode in a critical period of teen development can have lasting psychosocial repercussions. School is interrupted, budding careers nipped; people are shunned because they have been labeled as crazy.

The symptoms of schizophrenia include delusions, hallucinations, disordered thinking, movement disorders, flat affect, social withdrawal, and cognitive deficits. Before these overt symptoms develop, there may be prodromal signs or symptoms. PIER attempts to identify patients by prodromal symptoms before overt psychosis develops.

Common prodromal signs or symptoms can include the following, and it is important to note that a combination of symptoms rather than any one symptom would suggest a possible prodromal phase: Social withdrawal, a marked drop in functioning, uncharacteristic, peculiar behavior, increasing difficulty with concentration, heightened sensitivity to sights, sounds, smells or touch, loss of motivation or energy to participate in any activity, dramatic sleep and appetite changes, suspiciousness of others, unusual or exaggerated beliefs about personal powers or influences.

Some of these are characteristic of normal teens going through a bad patch. There is some overlap. Doctors who are looking for prodromes will have lower thresholds for deciding what behavior is peculiar and what constitutes a drop in functioning.

The most marked difference between prodrome and actual illness seems to be hallucinations, but hallucinations can also occur in normal people. It’s hard to draw a line where prodrome ends and illness begins. And we don’t know how many people fit the prodromal profile but never progress to psychosis.

We can identify risk factors even in people who don’t have prodromal symptoms. The risk factors currently identified by international research are:

Age: adolescence or early adulthood (12 – 30). The average age of a young person coming to our program is 17.
Family history of a psychotic disorder such as schizophrenia or bipolar disorder—particularly in a close or immediate relative (parent or sibling).
A history of difficulty making friends, along with unusual thoughts and odd or eccentric behaviors (schizotypal personality disorder).
A marked change in behavior, emotions, or thinking for a month or more, especially when accompanied by social withdrawal and deterioration in school or work performance.

These are only risk factors. They raise the probability of illness for the group but don’t predict illness for individuals. Two of them are objective, the other two subjective. The subjective ones are far from black and white. It’s hard to define things like “difficulty making friends,” or “a marked change in behavior.” Two observers might well come up with opposite answers. The two objective risk factors (age and heredity) can’t be changed. It’s not clear whether the two subjective ones are modifiable.

There are risk factors for diabetes, and there are measures that can be taken to reduce risk, such as weight reduction. There is also a prodrome with impaired glucose tolerance that is objectively measurable. Nevertheless, we don’t start pre-diabetics on insulin. We monitor them and advise health measures that would be good for them even if they had no risk of diabetes. We wait until they meet the criteria for diabetes before we treat.

According to one study, predictive algorithms for psychosis may reach an accuracy of 68-80%, “comparable to that in other areas of preventive medicine.” Is that good enough to justify this kind of intervention? I tend to agree with this analysis:

Early intervention” can refer to two different approaches–intervention when the psychosis is already evident and intervention before a psychosis is fully apparent. Each carries a distinctly different set of risks. The hoped-for benefits of early intervention in a fully evident psychosis are based on research that reveals an association between intervention early in the illness and good outcome. Those suffering from a psychosis of recent onset, however, are more likely to experience a spontaneous remission of illness, and this may readily explain the observed association. Early intervention in such cases of good-prognosis psychosis may lead to unnecessary and, sometimes, protracted treatment for those who would do well with no treatment. Intervention in the supposed prodromal phase of psychosis presents more serious hazards. The screening instruments currently available are inadequate for the accurate prediction of psychosis, and the risks of negative effects for the large numbers of people who screen false-positive are considerable. These risks include unnecessary fear of illness, restriction of life goals, use of medication and their side-effects.

The PIER website doesn’t offer unreliable testimonials, but it doesn’t offer any reliable references either, not even in the section for medical professionals. They say, “Early experience is showing that this approach clearly and dramatically reduces morbidity” but they have yet to publish any findings. What has been published in the medical literature doesn’t really support their approach.

A study of antipsychotics as sole prevention (by McGlashan et al.) gave inconclusive results. A study in Australia (by McGorry et al.) showed that risperidone plus psychotherapy was more effective at preventing psychosis than supportive care alone – but after the trial, several patients in the treatment group became psychotic, so the drugs may have been treating rather than preventing.

Neither McGlashan nor McGorry think the drugs should be used outside clinical trials. One researcher quoted in the Discover article said “current evidence does not support the use of antipsychotic medications as a prevention strategy in at-risk individuals.”

There are other things that really bother me. Schizophrenia as a diagnostic entity has been criticized as lacking in scientific validity or reliability.

Diagnosis depends largely on self-reports and on the reports of family members and others whose reports may not be reliable. Critics of psychiatry like Thomas Szasz think mental illness is a myth that is used by society to control people whose behavior doesn’t conform to society’s expectations. Mental illness was diagnosed for political purposes in the Soviet Union. In a famous experiment in the US, normal people got themselves admitted to a psychiatric hospital and found that they couldn’t shake the label: the staff continued to think they were crazy even though they behaved normally after admission.

The diagnosis of schizophrenia is so far from an exact science that the agreement between any two psychiatrists is only 65% or less. If the diagnosis of schizophrenia is this inaccurate, the diagnosis of prodromal symptoms must be even less exact. Using the prodromal diagnosis for prediction can’t be very accurate, and some normal people will inevitably be labeled incorrectly. Antipsychotic medications can cause serious side effects and even permanent damage, and we don’t want to give them to people who might not really need them.

On the one hand, if we can really prevent or delay the onset of psychosis we could alleviate a lot of suffering and give these young people a chance at a normal productive life. On the other hand, we might do more harm than good by overdiagnosing and overmedicating. Some say the illness is so devastating that we ought to do everything possible NOW, that we can’t afford to wait for better studies. Others say we’d better make sure of what we’re doing before we do any more of it. My opinion is that pharmaceutical interventions should take place only in a carefully designed research study. Meanwhile, we can still try to identify and help troubled young people.

PIER is doing much to foster public awareness of early psychotic symptoms. This is its real value. Maybe what we should be doing is educating the community, identifying young people with problems, involving their families, supporting them, helping them cope with the symptoms they currently have, and watching them for development of psychosis so they can be treated promptly and appropriately if and when the time comes – and not before.

For anyone who wants some insight into what these young people are going through, there is an excellent autobiographical book,  The Center Cannot Hold: My Journey Through Madness by Elyn Saks. It describes how she gradually became psychotic as a teenager, how she struggled with recurrent psychotic symptoms all her life, and how she tried all sorts of treatments and finally accepted that she needed to stay on medication. It’s particularly good at describing those in-between symptoms where it’s hard to say whether they are manifestations of disease or just part of life.

Posted in: Neuroscience/Mental Health, Pharmaceuticals, Science and Medicine

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