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Early intervention superior to treatment as usual for early-phase schizophrenia

Christoph U. Correll

Findings from a meta-analysis published in JAMA Psychiatry showed that early intervention services were superior to treatment as usual across all meta-analyzable outcomes in early-phase psychosis.

“The level of efficacy and effectiveness of [early intervention services] for patients with first-episode and early-phase schizophrenia spectrum disorders has been debated,” Christoph U. Correll, MD, of the department of psychiatry, Zucker Hillside Hospital, Glen Oaks, New York, and colleagues wrote. “To date, only one meta-analysis, which included four randomized clinical trials, has compared the effectiveness of [early intervention services] vs. treatment as usual for early-phase psychosis, indicating superiority of [early intervention services] approaches.”

The investigators searched clinical databases for randomized trials that compared early intervention services and treatment as usual in first-episode psychosis or early-phase schizophrenia spectrum disorders. Then, three independent researchers extracted data for a random-effects meta-analysis and prespecified subgroup, as well as for meta-regression analyses, to determine all-cause treatment discontinuation and at least one psychiatric hospitalization during the treatment period.

Overall, 10 randomized, control trials encompassing 2,176 patients met criteria and were included in this meta-analysis. In all trials, early intervention services were associated with better outcomes compared with treatment as usual at the end of treatment for all meta-analyzable outcomes. These outcomes included:

• all-cause treatment discontinuation (RR = 0.7; 95% CI, 0.61-0.8; P < .001);

• at least one psychiatric-related hospitalization (RR = 0.74; 95% CI, 0.61-0.9; P = .003);

• school or work involvement (RR = 1.13; 95% CI, 1.03-1.24; P = .01);

• total symptom severity (standardized mean difference [SMD] = –0.32; 95% CI, –0.47 to –0.17; P < .001);

• positive symptom severity (SMD = –0.22; 95% CI, –0.32 to –0.11; P < .001); and

• negative symptom severity (SMD = –0.28; 95% CI, –0.42 to –0.14; P < .001).

Furthermore, early intervention services showed superiority over treatment as usual for all outcomes at 6 months, 9 to 12 months and 18 to 24 months of treatment, excluding general and depressive symptom severity at 18 to 24 months. Post hoc meta-regression analysis showed that the overall attrition rate and between-group attrition difference did not mediate any of the outcomes, according to the authors.

“Additional trials are needed that study different [early intervention services] extension vs. step-down procedures for patient subgroups that can move between these options based on identified needs,” Correll and colleagues wrote. “Such research is especially relevant because data from 3 programs suggest that 2 to 3 years, 5 years, 7 to 8 years or 10 years after the discontinuation of [early intervention services], the prior gains may largely be lost.”

These findings further strengthen recent evidence that supports the effectiveness of early intervention services for first-episode psychosis; however, there are still challenges that must be addressed to avoid implementation failure, Patrick D. McGorry, MD, PhD, from the National Center of Excellence in Youth Mental Health, Melbourne, Australia, and colleagues wrote in an editorial.

“A long-term solution would be to adopt a transdiagnostic approach, compatible with both clinical staging and research domain criteria,” McGorry and colleagues wrote.

“Youth-friendly, stigma-free primary care portals for young people with undifferentiated needs, backed up with intensive community education, mobile detection, assertive treatment teams, and specialized streams of expert care are beginning to put this solution into practice,” they continued. “The goal would be to create a vertically integrated system of care, which could deliver [early intervention] and secure tenure of care during the critical period of transition to adulthood when the major mental disorders emerge and embed.” – by Savannah Demko

Disclosures: Correll reports being a consultant and/or advisor to or receiving honoraria from AbbVie, Actavis, Actelion, Alexza, Alkermes, Allergan, Bristol-Myers Squibb, Cephalon, Eli Lilly, Genentech, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante, Medscape, Merck, Neurocrine, Otsuka, Pfizer, ProPhase, Reviva, Roche, Sunovion, Supernus, Takeda, Teva and Vanda. He also reports grant support from the American Academy of Child and Adolescent Psychiatry, The Bendheim Foundation, Bristol-Myers Squibb, the NIMH, Novo Nordisk A/S, Otsuka, Takeda and the Thrasher Foundation. Please see the full study for all other authors’ relevant financial disclosures. McGorry reports support from a National Health and Medical Research Council Senior Principal Research Fellowship. Please see the full editorial for all other authors’ relevant disclosures.