Comparison of Early Intervention Services vs Treatment as Usual for Early-Phase Psychosis: A Systematic Review, Meta-analysis, and Meta-regression

Abstract

Importance: The value of early intervention in psychosis and allocation of public resources has long been debated because outcomes in people with schizophrenia spectrum disorders have remained suboptimal.

Objective: To compare early intervention services (EIS) with treatment as usual (TAU) for early-phase psychosis.

Data sources: Systematic literature search of PubMed, PsycINFO, EMBASE, and ClinicalTrials.gov without language restrictions through June 6, 2017.

Study selection: Randomized trials comparing EIS vs TAU in first-episode psychosis or early-phase schizophrenia spectrum disorders.

Data extraction and synthesis: This systematic review was conducted according to PRISMA guidelines. Three independent investigators extracted data for a random-effects meta-analysis and prespecified subgroup and meta-regression analyses.

Main outcomes and measures: The coprimary outcomes were all-cause treatment discontinuation and at least 1 psychiatric hospitalization during the treatment period.

Results: Across 10 randomized clinical trials (mean [SD] trial duration, 16.2 [7.4] months; range, 9-24 months) among 2176 patients (mean [SD] age, 27.5 [4.6] years; 1355 [62.3%] male), EIS was associated with better outcomes than TAU at the end of treatment for all 13 meta-analyzable outcomes. These outcomes included the following: all-cause treatment discontinuation (risk ratio [RR], 0.70; 95% CI, 0.61-0.80; P < .001), at least 1 psychiatric hospitalization (RR, 0.74; 95% CI, 0.61-0.90; P = .003), involvement in school or work (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). Superiority of EIS regarding all outcomes was evident at 6, 9 to 12, and 18 to 24 months of treatment (except for general symptom severity and depressive symptom severity at 18-24 months).

Conclusions and relevance: In early-phase psychosis, EIS are superior to TAU across all meta-analyzable outcomes. These results support the need for funding and use of EIS in patients with early-phase psychosis.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Correll reported 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. Dr Correll also reported receiving 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. Dr Craig reported being a consultant to and/or receiving honoraria from Sanofi and Otsuka and reported receiving grant support from the National Institute for Health Research and the Wellcome Trust. Dr Srihari reported receiving grant support from the NIMH and The Donaghue Foundation. Dr Chen reported serving on an advisory board for Janssen/J&J and reported receiving research funding and honoraria from Otsuka. Dr Schooler reported serving on advisory boards for or being a consultant to Allergan, Alkermes, Forum, Roche, and Sunovion and reported receiving grant support from Otsuka. Dr Kane reported being a consultant and/or advisor to or receiving honoraria from Alkermes, Allergan, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forum, Genentech, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, Medscape, Merck, Minerva, Neurocrine, Otsuka, Pierre Fabre, Pfizer, Reviva, Roche, Sunovion, Takeda, and Teva. Dr Kane also reported being a shareholder of MetAvante, LB Pharma, and the Vanguard Research Group. No other disclosures were reported.

Figures

Figure 1.. PRISMA Diagram of Included and Excluded Studies

EIS indicates early intervention services; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RCT, randomized clinical trial; and TAU, treatment as usual.

Figure 2.. Summary of Pooled Results

EIS indicates early intervention services; SMD, standardized mean difference; and TAU, treatment as usual.