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Are pharmacological and non-pharmacological interventions effective in preventing relapse in first-episode psychosis (FEP) patients?
The primary outcome was relapse, defined according to the criteria used in the individual studies.
Systematic review and meta-analysis.
CENTRAL, MEDLINE, MEDLINE Unindexed, EMBASE, PsycINFO, UMI Proquest Digital Dissertations, Information Science Citation Index Expanded, Information Social Sciences Citation Index, and Information Arts and Humanities Citation Index were searched from inception to December 2008. Additional studies were also identified using conference abstracts from ISI Science and Technology Proceedings and ISI Information Social Science and Humanities proceeding; hand searching of reference lists of retrieved trials, previous reviews and meeting abstracts; and contact with researchers and experts in the field.
Study selection and analysis
Randomised controlled trials (RCTs) of pharmacological and non-pharmacological interventions, where at least 75% of participants experiencing FEP diagnosed according to DSM or ICD criteria were included. A broad definition of FEP was used and could include schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, substance-induced psychotic disorder and psychotic disorder not otherwise specified. Eligible comparator interventions included: treatment as usual (TAU), placebo or an active comparator intervention. Trials were included if follow-up period was greater than 6 months.
Fifty-five studies were retrieved, 18 of which met eligibility criteria. Nine of the eligible studies involved psychosocial interventions, including three RCTs comparing specialist FEP programmes versus TAU, two RCTs comparing family therapy versus TAU and the remainder comparing different psychosocial programmes. Specialist FEP programmes reduced relapse events compared with TAU (3 RCTs, n=679; OR for relapse with TAU vs specialist FEP programme: 1.80, 95% CI 1.31 to 2.48, p<0.001; number needed to treat (NNT) approximately 8). Family therapy did not reduce relapse compared with TAU, and, likewise, cognitive behavioural therapy (CBT) did not provide a statistically significant advantages when compared with supportive counselling or TAU (see webextra table 1 for figures). The remaining nine studies involved pharmacological interventions, including three RCTs of first-generation antipsychotics (FGAs) versus placebo, four RCTs of second-generation antipsychotics (SGAs) versus FGAs, one RCT comparing different FGAs and one comparing treatment maintenance versus discontinuation. FGAs did not reduce relapse compared with placebo (3 RCTs, n=166; OR for relapse with placebo vs FGAs: 5.17, 95% CI 0.87 to 30.63, p=0.07). Overall SGAs reduced relapse compared with FGAs (OR FGAs vs SGAs: 1.47, 95% CI 1.07 to 2.01, p<0.02; NNT approximately 10).
Specialist programmes aimed at treating FEP are more effective at preventing relapse than is TAU, but family therapy and CBT are not. SGAs, as a class, are more effective at relapse prevention than are FGAs.
The study by Alvarez-Jiménez and colleagues, which explores effectiveness of pharmacological and non-pharmacological interventions to prevent relapse in patients with first-episode psychosis (FEP), is welcomed. Relapse following remission in FEP is common1 and represents an important treatment issue right from the onset of illness. However, interventions to prevent relapse are largely overlooked in FEP, and current treatment guidelines for FEP are generally not evidence based. Although medication discontinuation is highly prevalent in FEP,2 there is also little information to determine which patients can be successfully tapered off of antipsychotic medications without relapse.
This is the first study to systematically evaluate, through meta-analyses of randomised controlled trials, the efficacy of various interventions to prevent relapse in FEP. The most replicated findings were that (1) specialist FEP programmes are superior to treatment as usual in reducing relapse rates and hospital days in the first 2 years after illness onset and (2) second-generation antipsychotics are more effective to first-generation agents for relapse prevention. However, these findings are based on a relatively small number of studies and patients. Furthermore, the heterogeneity of diagnoses, interventions, pharmacologic agents and outcome measures between individual studies also limits the generalisability of the findings.
Nonetheless, this study represents an important effort to quantify the efficacy of various intervention strategies, as well as shape future research agendas. Given the adverse effects of psychotic relapse, the lack of well-conducted trials of psychosocial and pharmacologic interventions – alone and in combination – should serve as a resounding ‘call to arms’ to this field. As the Psychoses Workgroup for DSM-V (anticipated release in May 2013) is considering the addition of prodromal or high-risk psychosis as a diagnostic category, evidence for the efficacy of specialist FEP programmes aligns well with increased attention and efforts at early diagnosis. Furthermore, more information is needed to guide decisions regarding long-term maintenance of antipsychotic medications versus discontinuation in order to minimise the risk of relapse.
Sources of funding Marqués de Valdecilla Public Foundation – Research Institute (FMV-IFIMAV), Santander, Spain; Colonial Foundation; National Health and Medical Research Council of Australia.
Competing interests None.
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