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(PSYCHIATRIC TIMES) - It was not too long ago that the management of schizophrenia was generally viewed as pessimistic, and focused primarily on symptom relief. Over the past two decades, there has been a paradigm shift in our approach to the overall management of schizophrenia, toward preventive and early interventions. These approaches are being increasingly guided by recent pathophysiological models. In particular, it has become clear that neurobiological alterations are seen before onset of the illness (the premorbid phase) (Johnstone et al., 2002) and may progress during the early stages of the illness (the prodromal phase).

Further deterioration in brain structure and function may appear in some cases after characteristic symptoms of the illness begin (the psychotic phase), especially during the initial years. These observations suggest a critical window of opportunity, early in the illness, to effect lasting modifications in overall illness course (Keshavan et al., 2005a).

The three key questions for the field are:

1. Can schizophrenia be prevented in those at risk for the disorder (primary prevention)?
2. Can the first episode of psychosis be prevented in patients experiencing the prodromal phase of the illness (secondary prevention)?
3. Can we prevent relapses and further functional decline in patients who have already experienced the first episode of psychosis (tertiary prevention)?

Recent work, outlined below, suggests that considerable progress has been achieved in these areas over the years.
Prodromal Intervention

Primary prevention is best realized by removing a cause before the illness develops (e.g., preventing dental cavities by adding fluoride to the water). In schizophrenia, this remains speculative at best for now. The widely reported risk factors for schizophrenia include genetic factors, season and place of birth, pregnancy and birth complications, and antenatal exposure to viruses. Possible interventions for the families of genetically at-risk individuals include genetic counseling, prevention of viral infections during pregnancy and adequate prenatal care for women with schizophrenia.

In the future, it hopefully will be possible to design interventions that are specific to those individuals genetically at risk who display neurobehavioral and neurobiological precursors found by ongoing prospective studies to be accurate predictors of later illness (Keshavan et al., 2005b). For example, a program for an adolescent at genetic risk for schizophrenia who also displays cognitive and social deficits might include improvement of the home environment, prevention of abuse and neglect, a structured school environment combined with cognitive remediation, and possibly social skills training.

Secondary prevention strategies seek to prevent conversion to the full-blown psychotic illness in people experiencing the prodromal phase of the illness. The view that the attenuated psychotic-like symptoms characterizing the prodrome might be mediated by phasic dopaminergic excess has encouraged early treatment with low doses of dopamine-blocking drugs.

In a single-blind design, McGorry et al. (2002) compared low-dose risperidone (Risperdal) plus cognitive-behavioral therapy (CBT) with a needs-based intervention (i.e., counseling and case management) for six months. This was followed by a six-month observation period of all patients on needs-based therapy only. The combined specific intervention led to a significant preventive treatment effect in a modest sized population of 59 participants. Using a double-blind, randomized approach, Woods et al. (2003) compared the efficacy of olanzapine (Zyprexa) versus placebo. At eight weeks, a modest improvement was seen in symptoms associated with olanzapine treatment, though significant weight gain was also seen.

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