Psychosis in DSM-V: Innovations Likely

ISTANBUL, TURKEY — Look for a sweeping redefinition of schizophrenia and the other psychoses in the coming fifth edition of the Diagnostic and Statistical Manual of Mental Disorders.

DSM-V will very likely maintain the same nosologic categories and most of the same diagnostic criteria for the psychotic disorders as in DSM-IV, but with introduction of a major innovation: a parallel dimensions-of-pathology track that will be an essential part of individual patient evaluation.

“Clinicians, in addition to making a categorical diagnosis of schizophrenia, will also have to determine if the patient is depressed, rating depression on a simple 0-4 scale. They'll have to say, ‘Does this person have reality distortion; do they have disorganization of thought, cognitive impairment; do they have the negative symptom construct, the motor abnormalities?’” Dr. William T. Carpenter Jr. explained at the annual congress of the European College of Neuropsychopharmacology.

“We'll have about six dimensions of pathology that have side-by-side importance with the diagnostic category but are likely to define the therapeutic targets that clinicians will deal with and that we'll try to develop novel treatments for,” said Dr. Carpenter, who chairs the DSM-V psychosis work group.

Other domains under consideration for the dimensions-of-pathology track include depression, avolition, anxiety, mania, and restricted emotion.

“The evaluation will have to be brief. This has to be practical even in busy primary care settings. Specialized assessment techniques would be impractical. The one exception is cognitive impairment, but here a simple, quick test of processing speed, such as the digit-symbol test, carries a lot of the information that a more complicated neurocognitive examination would carry, and it takes just a minute or two,” noted Dr. Carpenter, director of the Maryland Psychiatric Research Center and professor of psychiatry at the University of Maryland, Baltimore.

Although he indicated that no final decisions have been made yet regarding the DSM-V chapter on psychosis, strong consensus exists among the working group that the dimensions-of-pathology system is sorely needed and would be a major step forward. It's an innovation that reflects an emerging paradigm shift in how schizophrenia is conceptualized.

For the last 100 years schizophrenia was seen as a single disease entity. That's clearly not the case. That's why the decades of research based upon this presumption have produced overall weak findings and only limited clinical benefit.

“The treatments that we have—primarily antipsychotic drugs—do reduce psychotic symptoms and relapse rates, but many aspects of the illness are not treated, and in the long term many patients will continue not to do well despite our treatments,” the psychiatrist observed.

He and his fellow DSM-V panelists believe the future of schizophrenia research and treatment lies in addressing the distinct dimensions of pathology present aside from psychosis. These vary from patient to patient and are only loosely related to one another.

The Food and Drug Administration has already given the green light to the dimensions-of-pathology paradigm. For decades, the only way the regulatory agency would approve a drug for schizo-phrenia was if it proved more effective than placebo at reducing psychotic symptoms. Not any more. The agency recently indicated that if a drug shows efficacy for a nonpsychotic dimension of pathology in the context of schizophrenia—say, cognitive impairment or diminished social interaction—then that medication can win approval.

The revised FDA stance has triggered a rush of pharmaceutical industry research activity, particularly targeting the impaired cognition dimension of schizo-phrenia, seen as low-hanging fruit. The disease typically results in loss of about 8 IQ points years before psychosis becomes manifest. Modafinil, glycine reuptake inhibitors, and histamine-3 receptor antagonists are among the agents that have successfully passed through the animal testing stage and are now in clinical trials for the improvement of impaired cognition in schizophrenia. Oxytocin is in patient testing as a treatment for diminished social interaction.

Dr. Carpenter said the most controversial proposal under consideration by the work group would create an entirely new diagnostic class: a risk syndrome for psychosis. It's based upon studies that have identified a population of young people at high risk for developing psychotic illness. These are individuals who seek medical help and display excessive suspiciousness, peculiar perceptual aberrations, and other possible prodromal manifestations of psychosis.

“The studies suggest on average about 30% of these individuals will move on to diagnosable psychotic illness within the next 2 years. So the question is, if 70% of them don't, are you doing more good than harm by trying to identify these individuals and intervene?” Dr. Carpenter observed.

He sees the incorporation of a risk syndrome for psychosis in DSM-V as an unmatched opportunity for early detection, amelioration, and possibly even prevention of major mental illness.

Others are deeply concerned about the prospect of false-positive diagnoses, excessive treatment, and possibly stigma.

“That's going to be a tough one for us. I don't know if we'll end up doing it,” he said. The stakes are high. Schizophrenia costs society more money than all cancers combined.

“The magnitude of the illness as a public health issue is just tremendous,” the psychiatrist noted in a wide-ranging press conference held in conjunction with his plenary address to the congress.

DSM-V is planned for May 2012 release. “It'll be a dynamic document. It will be possible to make changes without waiting for DSM-VI,” Dr. Carpenter said.