Evidence-Based Reviews

Early interventions for psychosis

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Despite considerable challenges, prevention and first-episode recovery programs may improve outcomes.



Neuroscience research over the past half century has failed to significantly advance the treatment of severe mental illness.1,2 Hence, evidence that a longer duration of untreated psychosis (DUP) aggravates—and early intervention with medication and social supports ameliorates—the long-term adverse consequences of psychotic disorders generated a great deal of interest.3,4 This knowledge led to the development of diverse early intervention services worldwide aimed at this putative “critical window.” It raised the possibility that appropriate interventions could prevent the long-term disability that makes chronic psychosis one of the most debilitating disorders.5,6 However, even beyond the varied cultural and economic confounds, it is difficult to assess, compare, and optimize program effectiveness.7 Obstacles include paucity of sufficiently powered, well-designed randomized controlled trials (RCTs), the absence of diagnostic biomarkers or other prognostic indicators to better account for the inherent heterogeneity in the population and associated outcomes, and the absence of modifiable risk factors that can guide interventions and provide intermediate outcomes.4,8-10

To better appreciate these issues, it is important to distinguish whether a program is designed to prevent psychosis, or to mitigate the effects of psychosis. Two models include the:

  • Prevention model, which focuses on young individuals who are not yet overtly psychotic but at high risk
  • First-episode recovery model, which focuses on those who have experienced a first episode of psychosis (FEP) but have not yet developed a chronic disorder.

Both models share long-term goals and are hampered by many of the same issues summarized above. They both deviate markedly from the standard medical model by including psychosocial services designed to promote restoration of a self-defined trajectory to greater independence.11-14 The 2 differ, however, in the challenges they must overcome to produce their sample populations and establish effective interventions.10,15,16

In this article, we provide a succinct overview of these issues and a set of recommendations based on a “strength-based” approach. This approach focuses on finding common ground between patients, their support system, and the treatment team in the service of empowering patients to resume responsibility for transition to adulthood.

The prevention model

While most prevention initiatives in medicine rely on the growing ability to target specific pathophysiologic pathways,3 preventing psychosis relies on clinical evidence showing that DUP and early interventions predict a better course of severe mental illness.17 In contrast, initiatives such as normalizing neonatal neuronal pathways are more consistent with the strategy utilized in other fields but have yet to yield a pathophysiologic target for psychosis.3,18

Initial efforts to identify ‘at-risk’ individuals

The prevention model of psychosis is based on the ability to identify young individuals at high risk for developing a psychotic disorder (Figure). The first screening measures were focused on prodromal psychosis (eg, significant loss of function, family history, and “intermittent” and “attenuated” psychotic symptoms). When applied to referred (ie, pre-screened) samples, 30% to 40% of this group who met criteria transitioned to psychosis over the next 1 to 3 years despite antidepressant and psychosocial interventions.19 Comprising 8 academic medical centers, the North American Prodrome Longitudinal Study (NAPLS) produced similar results using the Structured Interview for Prodromal Syndromes (SIPS).17 Thus, 30% to 50% of pre-screened individuals referred by school counselors and mental health professionals met SIPS criteria, and 35% of these individuals transitioned to psychosis over 30 months. The validity of this measure was further supported by the fact that higher baseline levels of unusual thought content, suspicion/paranoia, social impairment, and substance abuse successfully distinguished approximately 80% of those who transitioned to psychosis. The results of this first generation of screening studies were exciting because they seemed to demonstrate that highly concentrated samples of young persons at high risk of developing psychosis could be identified, and that fine-tuning the screening criteria could produce even more enriched samples (ie, positive predictive power).

Steps in identifying the population for prevention RCTs

Initial interventions produced promising results

The development of effective screening measures led to reports of effective treatment interventions. These were largely applied in a clinical staging model that restricted antipsychotic medications to those who failed to improve after receiving potentially “less toxic” interventions (eg, omega-3 polyunsaturated fatty acids and other antioxidants; psychotherapy; cognitive-behavioral therapy [CBT]; family therapy).5 While study designs were typically quasi-experimental, the interventions appeared to dramatically diminish the transition to psychosis (ie, approximately 50%).

Continue to: The first generation...


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