Elsevier

Psychiatry Research

Volume 262, April 2018, Pages 84-93
Psychiatry Research

Adjunctive therapy with statins in schizophrenia patients: A meta-analysis and implications

https://doi.org/10.1016/j.psychres.2018.02.018Get rights and content

Highlights

  • Adjunctive therapy with statins could improve psychiatric symptoms.

  • Adjunctive therapy with simvastatin is correlated to the negative symptoms reduction.

  • Psychiatric symptoms are changed by the duration of statins therapy.

  • High dose simvastatin is prone to negative symptoms decrease.

  • Compliant with antipsychotics of high P-gp affinity could improve psychiatric symptoms.

Abstract

There are some conflicting results regarding the benefit of adjunctive therapy with statins for severity of negative symptoms in schizophrenia. This study aimed to verify whether statins use for adjunctive therapy was indeed beneficial to improve psychiatric symptoms in schizophrenia. The data were from CENTRAL, PubMed, Embase and MEDLINE. The Boolean search term used for the electronic database search was (statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR mevastatin OR pitavastatin OR pravastatin OR rosuvastatin OR cerivastatin) and (schizophrenia OR schizoaffective disorder OR psychosis). Inclusion criteria were the following: RCTs, the adult schizophrenia patients, received antipsychotics plus statins or placebo, and the PANSS or SANS scores. Exclusion criteria were as follows: no data reported and multiple reports of the same study. A meta-analysis was used to compare psychiatric symptoms in schizophrenia patients with or without statins adjunctive therapy. The 6 RCTs included in the analysis represented 339 participants (169 in treatment group versus 170 in placebo group). A test for overall effect demonstrated that the PANSS positive scale and negative scale significantly reduced in participants receiving compliant with statins. Our meta-analyses first clarified that adjunctive therapy with statins could improve psychiatric symptoms, either negative symptoms or positive symptoms.

Introduction

Schizophrenia is considered as a serious mental disorder with positive and negative symptoms. It has been reported that the severity of negative symptoms, referred to poor emotional reactions or thought processes, is more related to poor quality of life, weak functional ability and heavy burden from families, than the severity of positive symptoms. However, the current antipsychotic medications of either first or second generation have little or no impact on primary negative symptoms though of being efficacious in alleviating the positive symptoms (Kirkpatrick and Galderisi, 2008). Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are effective cholesterol-lowering agents for treating CVD in the early stages of the disease (secondary prevention) and in those at elevated risk but without CVD (primary prevention). Because the prevalence of CVD in patients with schizophrenia is at two to three times higher than in the general population due to poverty, sedentary lifestyle, poor diet, reduced access to medical care and antipsychotics treatment (Fan et al., 2013). Statins are used to schizophrenia sufferers, particularly those taking antipsychotics to prevent CVD (Blackburn et al., 2017). To date, statins have been found with much wider usage. More attention had been focused on adjunctive therapy with statins to improve the negative symptoms of schizophrenia. However, the association between statins use and improvement of negative symptoms in schizophrenia is controversial. Tajik-Esmaeeli et al. (2017) reported that simvastatin use was associated with a significantly more reduction in negative symptoms score, when comparing the outcomes of the patients with chronic schizophrenia who received risperidone (4–6 mg/day) plus simvastatin with that of the placebo group. Data from two studies provided some evidences that statins (simvastatin (Deakin et al., 2014), atorvastatin (Sayyah et al., 2015) tended to improve negative symptoms without statistical significance. Furthermore, two other studies reported that the changes in PANSS negative symptoms score for the pateints with schizophrenia at endpoint were not statistically different between the adjunctive statins (lovastatin (Ghanizadeh et al., 2014), simvastatin (Chaudhry et al., 2014)) treatment and placebo groups. In contract, Vincenzi et al. (2014) reported that compared with the placebo group, the pravastatin group showed a significant reduction in the PANSS positive symptoms score.

The aims of this study were therefore to perform a between-group meta-analysis to compare psychiatric symptoms (negative and positive symptoms, general psychopathology) in schizophrenia patients with or without statins adjunctive therapy. Then, we verified firstly, if statins use for adjunctive therapy indeed reduced psychiatric symptoms; secondly, if the different classes of statins divergently modulated psychiatric symptoms; thirdly, whether the different types of antipsychotics were correlated with discrepant psychiatric symptoms. Lastly, we wanted to find out whether psychiatric symptoms were changed by the duration of statins therapy, ultimately clarifying the impact of adjunctive therapy with statins for schizophrenia.

Section snippets

Methods

The primary meta-analysis measured the effects of adjunctive therapy with statins on psychiatric symptoms of patients with schizophrenia, with follow-up periods ranging from 1 to 12 weeks. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and the Cochrane Collaboration.

Results

The literature search was performed from March to April 2017. A total of 190 records were identified from the initial search. The study inclusion and exclusion processes are showed in the flow diagram (Fig. 1). Finally, 6 unique studies were included in the meta-analysis.

Key characteristics are displayed in Table 1. We reviewed the included 6 studies by using a set of quality criteria developed by the Cochrane Centre. Based on this, we concluded that the included studies were of sound

Discussion

Our meta-analyses provided a novel insight into statins adjunctive treatment on psychiatric symptoms in patients with schizophrenia. Overall, pooled effects of 6 RCTs comprising 339 participants demonstrated the beneficial effect of statins adjunctive treatment on psychiatric symptoms, either negative symptoms or positive symptoms. In order to clarify this point, we conducted a series of sub-group analyses and verified that statins adjunctive treatments were associated with decreased

Acknowledgments

We gratefully acknowledge the authors and statisticians of the original studies, who sent us data or answered our queries.

Role of the funding source

There is no funding source.

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  • Cited by (0)

    1

    Hong Shen and Hong Xiao, as Corresponding author, contributed equally to this study.

    2

    Hong Shen and Rui Li, as the first author, contributed equally to this study.

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