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

ArticleinThe Lancet 379(9831):2063-71 · May 2012with85 Reads
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 Randomised trials of patients with schizophrenia continued on or withdrawn from any antipsychotic drug regimen after stabilisation were eligible.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.
    • "Schizophrenia is a devastating disease that has a chronic or intermittent course with numerous relapses over time [1]. Relapses of schizophrenia are known to adversely affect many biological functions [2] and antipsychotic treatment is pivotal for preventing relapses [3]. Anyway, in clinical setting patients' compliance to oral antipsychotics is often poor and difficult to maintain over time [4] , resulting in a heavy impact on the risk of relapse [5]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Recently, long-acting injection (LAI) of second-generation antipsychotics has become a valuable strategy for the treatment of schizophrenia. However, few studies have compared the effects of different LAI antipsychotics on cognitive functions so far. The present study aimed to compare the influence of risperidone LAIs (RLAI) and paliperidone palmitate LAIs (PP) on cognitive function in outpatients with schizophrenia. Methods: In this 6-month, open-label, randomized, and controlled study, 30 patients with schizophrenia who were treated with RLAIs were randomly allocated to the RLAI-continued group or the PP group. At baseline and 6 months, the patients were evaluated using the Brief Assessment of Cognition in Schizophrenia (BACS) that was the primary outcome of the study. The Subjective Well-being under Neuroleptic drug treatment-Short form (SWNS), the Positive and Negative Syndrome Scale (PANSS), and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) scores were secondary outcome variables and they were tested at the same time points. Results: The two groups did not differ in terms of PANSS, DIEPSS, or SWNS total score changes. However, the BACS score for the attention and processing speed item showed higher improvement in the PP group than the RLAI group (p = 0.039). Conclusions: The results of this preliminary study suggest that PPs may improve attention and processing speed more than RLAIs. Anyway, a replication in a larger and double-blind study is needed. Trial registration: UMIN000014470 . Registered 10 July 2014.
    Full-text · Article · Dec 2016
    • "Psychiatric disorders like schizophrenia and MDD have been primarily treated using pharmacotherapy such as with antipsychotic or antidepressant medications, both of which have been shown to reduce psychiatric symptoms (Leucht et al., 2012; Undurraga and Baldessarini, 2012). However, several large-scale meta-analyses have recently suggested that the effectiveness of antipsychotic and antidepressant medications is only marginally different from that of a placebo (Leucht et al., 2009; Rief et al., 2009), and neither have been able to successfully remediate cognitive dysfunction (Keefe et al., 2013Keefe et al., , 2014 Solé et al., 2015). "
    [Show abstract] [Hide abstract] ABSTRACT: Aerobic exercise (AE) has been widely praised for its potential benefits to cognition and overall brain and mental health. In particular, AE has a potent impact on promoting the function of the hippocampus and stimulating neuroplasticity. As the evidence-base rapidly builds, and given most of the supporting work can be readily translated from animal models to humans, the potential for AE to be applied as a therapeutic or adjunctive intervention for a range of human conditions appears ever more promising. Notably, many psychiatric and neurological disorders have been associated with hippocampal dysfunction, which may underlie the expression of certain symptoms common to these disorders, including (aspects of) cognitive dysfunction. Augmenting existing treatment approaches using AE based interventions may promote hippocampal function and alleviate cognitive deficits in various psychiatric disorders that currently remain untreated. Incorporating non-pharmacological interventions into clinical treatment may also have a number of other benefits to patient well being, such as limiting the risk of adverse side effects. This review incorporates both animal and human literature to comprehensively detail how AE is associated with cognitive enhancements and stimulates a cascade of neuroplastic mechanisms that support improvements in hippocampal functioning. Using the examples of schizophrenia and major depressive disorder, the utility and implementation of an AE intervention to the clinical domain will be proposed, aimed to reduce cognitive deficits in these, and related disorders.
    Full-text · Article · Aug 2016
    • "Antipsychotics are the mainstay of treatment for schizophrenia. Continued antipsychotic treatment has been shown to prevent relapse of psychotic symptoms and associated adverse consequences (Leucht et al., 2012; Wunderink et al., 2007). Also, early discontinuation of antipsychotics is associated with higher relapse rates in first episode psychosis (Chen et al., 2010; Wunderink et al., 2007). "
    [Show abstract] [Hide abstract] ABSTRACT: The dose of antipsychotic required for acute phase treatment of schizophrenia is well established, but there is no consensus on dose required for maintenance phase. Current guidelines do not provide definitive recommendations on the dose of antipsychotics needed in the maintenance treatment of schizophrenia, possibly due to limited research. In this retrospective study, minimum antipsychotic dose prescribed in maintenance treatment of schizophrenia in a real life situation was examined. Schizophrenia patients having Clinical Global Impression – Severity (CGI-S) ≤ 3 for at-least six months during the maintenance phase treatment were included (n=163). The medical records of these patients were reviewed and the antipsychotic dose prescribed for acute and maintenance phase treatment was recorded. The mean antipsychotic dose used during maintenance treatment was approximately 30% lower than the dose used during acute phase. Importantly, about 40% of the subjects maintained well with a dose lesser than the recommended therapeutic range. Earlier age at onset and longer duration of illness were associated with higher antipsychotic dose requirement during the maintenance phase treatment. These findings could have important clinical implications if replicated in systematic prospective studies.
    Full-text · Article · Aug 2016 · Frontiers in Human Neuroscience
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