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Interventions in the Subthreshold Stage

Current early intervention strategies range from the psychologically based, including psychoeducation, supportive psychotherapy, cognitive behavioral therapy (CBT), and family work, to the biologically based, including symptomatic treatment for depression, anxiety, and any subthreshold psychotic symptoms, through to experimental neuroprotective approaches. The global aim of treatment in the prodromal phase is to provide comprehensive clinical care designed to reduce presenting symptoms and improve functioning and, if possible, to prevent these symptoms from worsening and developing into fully fledged and sustained psychosis. If a first episode of psychosis does occur, the aims of treatment are to minimize the duration of untreated psychosis, to attain and maintain remission of psychotic symptoms, and to promote maximum recovery without residual disability.

Ten intervention studies have now been conducted with ultra-high risk young people worldwide investigating the use of medications (low-dose anti- psychotics and/or antidepressants), psychosocial treatments, or both, to prevent the onset of psychosis. A recent meta-analysis of these trials has shown that each of these treatments is effective, with an overall number needed to treat of nine (95% confidence interval [CI] 6-15) and an overall risk reduction at 12 months of 54%.46 However, risk-benefit concerns related to the use of antipsychotic medication, even at low doses, means that psychosocial interventions, including supportive therapy, CBT, and other benign interventions (such as treatment with omega-3 fatty acids),47 are currently recommended as first-line therapy for this patient group. Drug therapies should only be considered if symptoms and impairment persist or worsen. Antipsychotic medication may have a place in the treatment of those who fail to respond to initial intervention with psychosocial therapies. Of note, symptom severity alone may not be a perfect guide for the need for antipsychotic medication. Other factors, such as symptom type and pattern, and other clinical phenomena, including comorbid substance use, triggers and stressors, and genetic and other biomarkers, will also determine the optimal treatment for a given patient. When antipsychotic medications are prescribed, the best candidates are those with a more favorable metabolic and neurological safety profile.48 To date, the results of the intervention trials in ultra-high risk patients are promising, but there is a need to study other strategies, such as cognitive remediation and benign biotherapies targeting candidate neurobiological mechanisms, such as inflammation and oxidative stress. Determination of the optimal sequence of interventions and definition of therapeutically relevant subgroups via sophisticated clinical trial designs are necessary to build a solid evidence base to inform future therapeutic strategies.

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