Metabolic side effects of antipsychotic drugs in individuals with schizophrenia during medium- to long-term treatment: protocol for a systematic review and network meta-analysis of randomized controlled trials

Abstract Background Antipsychotic drugs and especially the newer compounds are known to cause metabolic side effects. However, a comprehensive comparison of the different substances regarding their propensity to cause metabolic side effects in medium- to long-term treatment of schizophrenia is lacking. Methods We will conduct a systematic review and network meta-analysis (NMA). We will include randomized controlled trials (RCTs) in which participants received either placebo or an antipsychotic (i.e. placebo-controlled trials and head-to-head comparisons of drugs). We will include studies in individuals with schizophrenia or related disorders (such as schizophreniform or schizoaffective disorders) at any stage of the disease (acute episode; maintenance phase). We will include studies with a duration of more than 3 months (medium- to long-term treatment). The primary outcome will be the change in body weight. Secondary outcomes will be the further metabolic parameters: fastening glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides. We will search for eligible studies (independent of the publication status) in Cochrane Schizophrenia Group’s Study-Based Register of Trials, which is compiled by regular searches in trial registries and multiple electronic databases from their inception onwards including MEDLINE, EMBASE and PsycINFO. Additionally, we will search previously published systematic reviews and websites of pharmaceutical companies for eligible studies. At least two reviewers will independently conduct the process of study selection and data extraction. We will use the Cochrane Risk of Bias 2 tool to evaluate the risk of bias in studies. We will conduct random-effects NMA within a Bayesian framework to synthesize all evidence for each outcome. We will conduct sensitivity and subgroup analyses to assess the robustness of the findings and to explore heterogeneity. The confidence in the results will be evaluated using the Confidence in Network Meta-Analysis (CINeMA) framework. Discussion This systematic review and network meta-analysis will provide a synthesis of the existing evidence from RCTs how antipsychotic drugs differ in terms of metabolic side effects during medium- to long-term treatment. The findings have the potential to influence the choice of antipsychotic medication made by individuals with schizophrenia and their physicians. Systematic review registration PROSPERO CRD42020175414

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Do antipsychotic drugs lose their efficacy for relapse prevention over time?

The British Journal of Psychiatry ◽

10.1192/bjp.bp.117.201103 ◽

2017 ◽

Vol 211 (3) ◽

pp. 127-129 ◽

Cited By ~ 13

Author(s):

Stefan Leucht ◽

John M. Davis

Keyword(s):

Relapse Prevention ◽

Antipsychotic Drugs ◽

Meta Analysis ◽

Term Treatment ◽

First Episode ◽

Brain Volume Loss ◽

New Findings ◽

Long Term Treatment ◽

Long Term Follow Up

SummaryThere is a debate about long-term treatment of schizophrenia with antipsychotic drugs, with some experts suggesting that these drugs should be discontinued. In this issue, Takeuchi et al demonstrated by a meta-analysis of 11 trials that antipsychotic drugs maintained their efficacy for relapse prevention for 1 year, whereas patients on placebo kept getting worse. We consider these findings in the light of the current discussion about possible dose-related brain volume loss, supersensitivity psychosis, the high variability of results in long-term follow-up studies and recent approaches to discontinue antipsychotics in patients with a first-episode. The new findings speak in favour of continuing antipsychotics at the same dose, at least in patients whose condition is chronic, but the topic is complex.

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Efficacy of Low- molecular- weight- heparin versus Vitamin K antagonists for long term treatment of cancer-associated venous thromboembolism in adults: A systematic review of randomized controlled trials

Thrombosis Research ◽

10.1016/j.thromres.2008.09.002 ◽

2009 ◽

Vol 123 (6) ◽

pp. 837-844 ◽

Cited By ~ 59

Author(s):

Martha L. Louzada ◽

Habeeb Majeed ◽

Philip S. Wells

Keyword(s):

Systematic Review ◽

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Vitamin K Antagonists ◽

Term Treatment ◽

Controlled Trials ◽

Low Molecular Weight ◽

Randomized Controlled ◽

Long Term Treatment

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No Metabolic Side Effects of Long-Term Treatment with Verapamil in Hypertension

Angiology ◽

10.1177/000331978803901204 ◽

1988 ◽

Vol 39 (12) ◽

pp. 1025-1029 ◽

Cited By ~ 13

Author(s):

Kjell Midtbø ◽

Oddveig Lauve ◽

Ottar Hals

Keyword(s):

Side Effects ◽

Term Treatment ◽

Metabolic Side Effects ◽

Long Term Treatment

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The effect of monoamine oxidase-B inhibitors on the alleviation of depressive symptoms in Parkinson’s disease: meta-analysis of randomized controlled trials

Therapeutic Advances in Psychopharmacology ◽

10.1177/2045125320985993 ◽

2021 ◽

Vol 11 ◽

pp. 204512532098599

Author(s):

Yao Hsien Huang ◽

Jia Hung Chen ◽

El Wui Loh ◽

Lung Chan ◽

Chien Tai Hong

Keyword(s):

Depressive Symptoms ◽

Early Stage ◽

Meta Analysis ◽

Term Treatment ◽

Monoamine Oxidase B ◽

Controlled Trials ◽

Short Term ◽

Randomized Controlled ◽

Long Term Treatment

Background: Depression is a major nonmotor symptom of Parkinson’s disease (PD). However, few treatments exist for PD depression. Monoamine oxidase-B inhibitors (MAOB-Is) provide symptomatic relief for the motor symptoms of PD and exert antidepressive effects. The present meta-analysis of randomized controlled trials (RCTs) investigated the effects of MAOB-Is on depressive symptoms in patients with PD. Methods: Articles on PD-management-related RCTs using one of three MAOB-Is approved by the US Food and Drug Administration, that is, selegiline, rasagiline, and safinamide, were identified. The primary outcomes were the benefits of MAOB-Is for depressive symptoms. Subgroup analysis included the effects of MAOB-Is on patients in the early versus middle-to-late stages of PD and the effect of short-term versus long-term treatment. Results: Overall, six studies were included, four of which were conducted on patients with early stage PD. Overall, MAOB-Is significantly reduced the severity of depressive symptoms [standardized mean difference (SMD): −0.14, 95% confidence interval (CI): −0.21 to −0.06, p < 0.001]. Subgroup analysis indicated that the positive effect of MAOB-Is was significant in patients with early stage PD (SMD: −0.20, 95% CI: −0.31 to −0.09, p < 0.001), but not in those with middle-to-late-stage PD (SMD: −0.07, 95% CI: −0.17 to 0.03, p = 0.18). The antidepressive effect was significant for short-term treatment, that is, 90–120 days (SMD: −0.23, 95% CI: −0.35 to −0.10, p < 0.001), but not long-term treatment, that is, 24 weeks to 18 months (SMD: −0.08, 95% CI: −0.18 to 0.01, p = 0.09). Conclusion: In addition to the treatment of PD motor symptoms, MAOB-Is may help reduce the severity of depressive symptoms in PD, especially in patients with early stage PD. Considering the tolerability and simultaneous benefits of MAOB-Is, further RCTs are warranted to confirm their therapeutic effects in moderate-to-severe PD depression.

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