Jury Out on Early Intervention for Psychosis

Megan Brooks

June 17, 2011

June 17, 2011 — There is "emerging, but as yet inconclusive" evidence that individuals in the prodromal phase of psychosis can benefit from early intervention, although whether this will prevent progression to full-blown schizophrenia remains to be seen, conclude the authors of a new Cochrane review.

There is also "some support for phase-specific treatment focused on employment and family therapy, but again, this needs replicating with larger and longer trials," authors Max Marshall, MD, University of Manchester, and John Rathbone, MD, University of Sheffield, United Kingdom, write.

The review appears in the latest issue of the Cochrane Library, a publication of the Cochrane Collaboration, an international organization that evaluates medical research.

Proponents of early intervention argue that schizophrenia outcomes may be improved if more efforts were focused on the early phase of psychosis. It's estimated that about 10% to 20% of these individuals go on to develop full-blown schizophrenia. The aim of early intervention is to prevent this.

"The arguments in favor of early intervention have been so persuasive that early intervention teams are well-established in America, Europe and Australasia," the authors note.

Early intervention in schizophrenia has 2 distinct goals. The first is the early identification of those likely to develop psychosis. These individuals display nonpsychotic prodromal symptoms but have never had a psychotic episode.

The second is phase-specific treatment that may include psychological, social, or physical treatment designed specifically for patients with early-stage illness. Early detection and phase-specific treatment may supplement standard care or may be provided through a specialized early intervention team.

However, clear-cut evidence of effectiveness of early intervention remains unclear, the authors note.

Omega-3 Therapy 'Interesting'

The Cochrane review team identified and analyzed 18 relevant randomized controlled trials that included a total of 1808 patients. The studies were diverse and mostly small and had "many methodological limitations," they report.

Six of the studies focused on preventing progression to psychosis in patients showing nonpsychotic prodromal symptoms.

In 1 of these studies involving 60 patients, olanzapine "seemed of little benefit" in preventing conversion to psychosis (relative risk [RR], 0.58; 95% confidence interval [CI], 0.3 - 1.2). Cognitive-behavioral therapy (CBT) seemed equally ineffective in keeping psychosis at bay in 1 study of 60 patients (RR for conversion, 0.50; 95% CI, 0.2 - 1.7).

One study of 59 patients provided some evidence that combining risperidone with CBT and specialized team care was more effective than specialized team care alone at preventing conversion to psychosis at 6 months (RR, 0.27; 95% CI, 0.1 - 0.9). The number needed to treat (NNT) to prevent 1 conversion was 4 (95% CI, 2 - 20). However, the benefit did not seem to be maintained at 12 months (RR, 0.54; 95% CI, 0.2 - 1.3).

Perhaps most interesting, the reviewers say, is a study of omega-3 fatty acids. In this study of 76 patients, those who received omega-3 fatty acids (instead of placebo) were significantly less likely to develop psychosis (RR for transition to psychosis, 0.13; 95% CI, 0.02 - 1.0). "A NNT of 6 in a sample of 76 is an important result," they write.

"The omega-3 study is perhaps the most interesting conceptually (what is the neurobiology behind it?), and it needs to be replicated urgently, ideally in a very large sample," Oliver Freudenreich, MD, who was not involved in the Cochrane review, told Medscape Medical News. He is director of the First Episode and Early Psychosis Program at Massachusetts General Hospital in Boston.

Widespread Screening 'Premature'

The remaining 11 studies focused on improving outcome after the first episode of psychosis. The interventions included diverse phase-specific treatment approaches, coupled, for the most part, with standard medications.

The researchers say the largest (n = 547) and highest-quality study compared standard care with specialized team care that provided a range of psychosocial therapies. It found that patients in specialized care did better in the first year than did those in standard care. They were less likely to leave the study early (RR, 0.59; 95% CI, 0.4 - 0.8) and more apt to adhere to treatment (RR for stopped treatment, 0.20; 95% CI, 0.1 - 0.4). However, the differences waned later on.

Adding family therapy or vocational counseling to specialized care seemed to provide some benefit, the authors note.

"Family intervention may be of value for people in their first episode of psychosis as it may for people with longer established illnesses. It is important for clinicians to continue to keep up to date with this fast-expanding field."

In a 56-patient study, phase-specific CBT for suicidality plus specialized team care showed little benefit, with about a 20% reduction in the RR for suicide (RR, 0.81).

In the other studies, phase-specific treatments showing no benefit included cannabis and psychosis therapy, ethyl-eicosapentaenoic acid, and Adherence Coping Education and crisis assessment.

"At the moment it is not clear whether treating people presenting with prodromal symptoms of schizophrenia provides benefits. There is inconclusive evidence on the personal and social consequences of providing treatment to people who will not necessarily become unwell," they write.

"It is premature to implement wide-spread treatment programs for people with prodromal symptoms," they conclude.

However, they note that for patients experiencing their first episode of psychosis, there is "some support for specialized early intervention services but again further evidence is needed."

Dr. Freudenreich added there were "no real surprises" in the review. The "take home," he said, is that the literature is inconclusive.

However, he added he was "somewhat surprised that a Cochrane review was even attempted given the few [published] studies. It still feels like we are doing pilot studies. The obvious action point is that much larger (multisite) studies are needed."

Cochrane Database Syst Rev. 2011;6:CD004718. Abstract