Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: A systematic review and meta-analysis

Department of Psychiatry and Psychotherapy, Technische Universität München, Klinikum rechts der Isar, Munich, Germany.
The Lancet (Impact Factor: 45.22). 05/2012; 379(9831):2063-71. DOI: 10.1016/S0140-6736(12)60239-6
Source: PubMed


Relapse prevention with antipsychotic drugs compared with placebo in patients with schizophrenia has not been sufficiently addressed by previous systematic reviews. We aimed to assess the association between such drugs and various outcomes in patients with schizophrenia to resolve controversial issues.
We searched the Cochrane Schizophrenia Group's specialised register for reports published before Nov 11, 2008; and PubMed, Embase, and for those before June 8, 2011. We also contacted pharmaceutical companies and searched the reference lists of included studies and previous reviews. Randomised trials of patients with schizophrenia continued on or withdrawn from any antipsychotic drug regimen after stabilisation were eligible. Our primary outcome was relapse between 7 and 12 months. We also examined safety and various functional outcomes. We used the random effects model and verified results for the primary outcome with a fixed effects model. Heterogeneity was investigated with subgroup and meta-regression analyses.
We identified 116 suitable reports from 65 trials, with data for 6493 patients. Antipsychotic drugs significantly reduced relapse rates at 1 year (drugs 27%vs placebo 64%; risk ratio [RR] 0·40, 95% CI 0·33-0·49; number needed to treat to benefit [NNTB] 3, 95% CI 2-3). Fewer patients given antipsychotic drugs than placebo were readmitted (10%vs 26%; RR 0·38, 95% CI 0·27-0·55; NNTB 5, 4-9), but less than a third of relapsed patients had to be admitted. Limited evidence suggested better quality of life (standardised mean difference -0·62, 95% CI -1·15 to -0·09) and fewer aggressive acts (2%vs 12%; RR 0·27, 95% CI 0·15-0·52; NNTB 11, 6-100) with antipsychotic drugs than with placebo. Employment data were scarce and too few deaths were reported to allow significant differences to be identified. More patients given antipsychotic drugs than placebo gained weight (10%vs 6%; RR 2·07, 95% CI 2·31-3·25), had movement disorders (16%vs 9%; 1·55, 1·25-1·93), and experienced sedation (13%vs 9%; 1·50, 1·22-1·84). Substantial heterogeneity in size of effect was recorded. In subgroup analyses, number of episodes, whether patients were in remission, abrupt or gradual withdrawal of treatment, length of stability before trial entry, first-generation or second-generation drugs, and allocation concealment method did not significantly affect relapse risk. Depot preparations reduced relapse (RR 0·31, 95% CI 0·21-0·41) more than did oral drugs (0·46, 0·37-0·57; p=0·03); depot haloperidol (RR 0·14, 95% CI 0·04-0·55) and fluphenazine (0·23, 0·14-0·39) had the greatest effects. The effects of antipsychotic drugs were greater in two unblinded trials (0·26, 0·17-0·39) than in most blinded studies (0·42, 0·35-0·51; p= 0·03). In a meta-regression, the difference between drug and placebo decreased with study length.
Maintenance treatment with antipsychotic drugs benefits patients with schizophrenia. The advantages of these drugs must be weighed against their side-effects. Future studies should focus on outcomes of social participation and clarify the long-term morbidity and mortality of these drugs.
German Ministry of Education and Research.

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    • "A recent review revealed that, after relapse, response is delayed in some patients and a subgroup of about 1 in 6 patients displays emergent refractoriness (Emsley et al., 2013). There is sound evidence that antipsychotic maintenance treatment (MT) reduces the risk for relapse substantially (Leucht et al., 2012). However, antipsychotic treatment, especially in long-term use, shows also adverse effects, e.g. "

    • "Relapses and rehospitalization of schizophrenic and schizoaffective patients lead to proven negative consequences, in terms of course, treatment, prognosis, and impact on the health care system (Higashi et al. 2013; Novick et al. 2010). Since complete symptom relief and relapse prevention are considered as the main goals in the long-term treatment of these conditions (Lehman et al. 2004), maintenance antipsychotic treatment is recommended to minimize the relapse and readmission risk (Carpenter et al. 1990; Leucht et al. 2012). However, the benefits of maintenance treatment are often compromised by the high rates of non-adherence to antipsychotic therapy in these disorders (Higashi et al. 2013; Novick et al. 2010). "
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    ABSTRACT: Objective: To present real-world preliminary evidence on the specific effects of switching from oral to long-acting injectable (LAI) antipsychotic treatment on patient's subjective experience and quality of life (QoL) in a sample of clinically stable psychotic subjects. Methods: Twenty-six clinically stable adult schizophrenic and schizoaffective outpatients were recruited. All patients were under a stabilized therapy with a single oral second-generation antipsychotic and were switched to the equivalent maintenance regimen with the long-acting formulation of the same antipsychotic. Two subgroups of patients were created on the basis of the presence/absence of a complete clinical remission at enrollment. Anthropometric (body mass index), psychometric (Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale, and Positive And Negative Syndrome Scale), and patient's reported outcome (Subjective Well-Being Under Neuroleptics scale short form, Drug Attitude Inventory short version, and Short Form-36 health survey) data were collected at enrollment (T0) and after 6 months from the treatment switch (T1). Results: Significant improvements in psychometric indexes, and patients' subjective experience of treatment and attitudes toward drug (reflecting in an enrichment of patients' health-related QoL) were found both in initial remitters and non-remitters. Conclusions: Our preliminary results suggest that the switch from oral to LAI antipsychotic treatment may help to address the subjective core of an optimal and satisfying recovery of psychotic patients. Size and duration of this study need to be expanded in order to produce more solid and generalizable results.
    International Journal of Psychiatry in Clinical Practice 11/2014; 19(2):1-24. DOI:10.3109/13651501.2014.988268 · 1.39 Impact Factor
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    • "STUDIES WITH LONGER FOLLOW-UP Wunderink, Nieboer, Wiersma, Sytema, and Nienhuis (2013) examined both the short and long term efficacy of antipsychotic treatment for first episode schizophrenia. Wunderink et al. acknowledged that the literature suggested that for the first two years after the emergence of psychosis, those who continue on medications have lower rate of relapse than those who discontinue their medications (see Leucht et al., 2012). However, Wunderink et al. wanted to examine how medications influence the longer term outcomes. "
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    ABSTRACT: In recent decades the understanding of the core physiology giving rise to schizophrenia has advanced markedly. Current pharmacological interventions fail to target the core problems in schizophrenia. Several important outcome studies call into question whether current medications actually make long-term outcomes worse. These new studies follow the recognized negative side effect of anti-psychotic drugs. The implication of these findings for social workers who work with the seriously mentally ill are discussed. Alternatives to current pharmacological treatments that are more targeted toward the core physiology of schizophrenia are reviewed.
    Social Work in Mental Health 06/2014; 12(4):365-385. DOI:10.1080/15332985.2014.894487
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