The PIER program relies on community networks to flag vulnerable patients and bring them in for treatment. Clinicians, social workers, teachers, and others who routinely work with young people are taught to recognize schizophrenia’s early warning signs, which include paranoia, disorganized thought, fleeting hallucinations, social alienation, and a sudden loss of interest in activities. Admission to the program starts with a phone interview. Nearly 60 percent of those who move past that initial screening to a diagnostic assessment in person are accepted and supplied with a two- to four-year treatment regimen for free.
The approach employs a mix of psychosocial measures aimed at limiting the patient’s emotional stress load. Precisely how such stress can lead to a psychotic break isn’t understood, but scientists do know schizophrenia has complex genetic and environmental components. Since the inherited risk is based in family genetics and is therefore beyond clinical reach, McFarlane relies on multifamily group therapy and social supports at school and at work to protect vulnerable patients from environmental triggers—illicit drugs and emotional stress in particular—that might send them over the edge. Over time, most patients learn how to manage their condition, just as patients with chronic diseases such as diabetes learn to monitor symptoms and medications.
McFarlane describes the case of one patient who felt her symptoms returning after a weekend party. At school on Monday, the young woman noticed that “things seemed strange,” he says. “Noises were disturbing her, lights seemed too bright, and she began to worry she was slipping. So she gave us a call, and we told her to take it easy for a few days; we reminded her to take her medication and to get enough sleep, to reduce her stress load below normal. And she did that, and those symptoms started to diminish. So she realized she could use those symptoms as a marker or indicator, almost the way a diabetic might look at blood sugar.”
In this multipronged approach, only the early use of medication worries McFarlane’s skeptics. Antipsychotics, particularly drugs like olanzapine (marketed as Zyprexa), have severe metabolic side effects, which include weight gain and other changes that heighten the risk of diabetes. Long-term use of all antipsychotics can also cause uncontrollable movements known as tardive dyskinesia. The newest antipsychotics, including aripiprazole (Abilify), appear to have far less metabolic risk. Camila, who gained weight on Zyprexa, says she has lost it on Abilify.
Still, many psychiatrists insist antipsychotics shouldn’t be given without a confirmed diagnosis of a psychotic disorder. “We just don’t know enough yet about the risks and benefits of antipsychotics, particularly in children and adolescents,” warns Diana Perkins, a psychiatrist at the University of North Carolina at Chapel Hill. “My concern is that using them for prevention is premature.” Perkins points out that antipsychotics block dopamine receptors in the brain, which can also have the effect of depressing estrogen and testosterone levels. Whether that has any impact on development isn’t known. “What little data we have suggest sexual development might be altered, but the evidence base for that assumption is weak,” Perkins says.
The debate underscores how little is known about the biological origins and onset of schizophrenia itself, as well as how best to treat its early stages. McFarlane’s approach raises two basic questions. The first is whether a set of symptoms can reliably predict the onset of full-blown psychosis. Some scientists use the term prodromal to describe someone who seems headed toward the disorder, but the medical community has not yet formally accepted this as a diagnosable, treatable condition. Symptoms considered prodromal (the term comes from the Greek for “running ahead”) vary from patient to patient. Camila displayed some classic prodromal indicators: An otherwise healthy kid, she was suddenly victimized by minor hallucinations and paranoia and withdrew from social interaction. But schizophrenia often strikes during adolescence, a time when—as any parent knows—bizarre behaviors are all too common.
Research released just this past January delivered the most recent evidence that prediction of psychosis is possible. According to a nationwide study of 291 patients coordinated by the NIMH, prodromal symptoms predict the onset of psychosis 35 percent of the time, which is comparable with the prediction rate for type 2 diabetes. But Robert Heinssen, who is chief of the Adult Treatment and Preventive Intervention Research Branch at the NIMH and who led the study, claims that prodromal symptoms, when considered in the context of a full medical history, can produce a much more accurate prediction. “We found it can soar to 81 percent if additional features are present, like a family history of psychotic illness, odd or weird thoughts, and severe social deficits, such as having no friends or withdrawing from contact with others,” he says.
The second question is whether antipsychotic medication is an appropriate treatment for preventing the onset of psychosis. While Perkins expresses concerns about the risk of the drugs, Cameron Carter, a psychiatrist and brain researcher at the University of California at Davis, sees the problem differently. If doctors can foretell schizophrenia, he says, then the benefits of preventive drug treatment outweigh the risks of side effects. “It’s likely the side effects would be far less damaging than the psychosis itself,” he says.
Over the following months, almost none of the handful of at-risk patients converted to psychosis. “It all went incredibly well,” McFarlane says. “So we thought, ‘This is worth doing,’ and we started looking for funding.”
McFarlane has not published any results from his program, and other data relating to antipsychotics in prevention are not definitive. McGlashan’s clinical trial with olanzapine to prevent psychosis remains the only one yet to investigate antipsychotics as the sole intervention. Conducted from 1999 to 2004 in a population of 60 patients (29 treated and 31 controls), that study produced statistically inconclusive results, in part because too many drug-treated patients dropped out complaining of weight gain. An earlier study performed in 2002 by Patrick McGorry, from the University of Melbourne in Australia, found that an antipsychotic called risperidone plus psychotherapy was more effective at preventing psychosis than supportive care alone. After his six-month trial ended, however, several patients in the treatment group became psychotic, raising the question of whether the treatment was preventing schizophrenia or simply controlling its symptoms.
During interviews for this article, neither McGlashan nor McGorry backed the use of antipsychotics in prevention outside of clinical trials. Likewise, Heinssen says that “current evidence does not support the use of antipsychotic medications as a prevention strategy in at-risk individuals.” Heinssen adds that NIMH is not preparing any clinical trials to investigate the preventive use of antipsychotic medication. The research effort he directs focuses on entirely new compounds that might slow the loss of brain cell connections, which may play a role in schizophrenia biology.
