Statins for major depressive disorder: A systematic review and meta-analysis of randomized controlled trials

Giorgi, Riccardo; Crescenzo, Franco De; Pesci, Nicola Rizzo; Martens, Marieke; Howard, Wendy L.; Cowen, Philip J.; Harmer, C J

doi:10.1371/journal.pone.0249409

Cited by 32 publications

(40 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They both included 3 RCTs ( 133 – 135 ) and found a significant improvement in depressive symptoms [SMD = −0.73, 95% CI = −1.04 to −0.42 ( 130 ); SMD = −0.65, 95% CI = −0.96 to −0.33 ( 19 )] associated with statins add-on. A more recent meta-analysis added a further RCT ( 132 ) and confirmed the above results (SMD = −0.48, 95% CI = −0.74 to −0.22], whilst also supporting the acceptability, tolerability, and safety of statins in the treatment of depression ( 71 ).…”

Section: Resultsmentioning

confidence: 65%

“…For example, all the retrieved RCTs (133-135) that employed a lipophilic statin (respectively, lovastatin, atorvastatin, and simvastatin) in depressed patients observed an improvement of depressive symptoms, whereas the only trial that could not replicate this effect used the hydrophilic molecule, rosuvastatin (132). Interestingly, simvastatin, the most lipophilic statin, showed a more pronounced antidepressant effect compared to the less lipophilic atorvastatin in another RCT (131) and fared better than any other statin in a recent exploratory network meta-analysis (71). Likewise, evidence from most observational studies in non-depressed populations reported that simvastatin had the most beneficial effects (87,90), though another study reported a conflicting finding (76).…”

Section: Discussionmentioning

confidence: 99%

“…We conducted an extensive literature search of the PubMed/MEDLINE, Cochrane CENTRAL, ISI Web of Science, CINAHL, and ClinicalTrials.gov databases from the date of inception until the 9th of April 2021, including non-English language articles. We used a well-validated search algorithm (PROSPERO international prospective register of systematic reviews reference CRD42020170938, available at https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=170938 ) based on our previously conducted systematic review and meta-analysis of randomised controlled trials ( 71 ), which combined all the relevant terms for statins, depression, and antidepressants ( Supplementary Material ). References of the included papers were manually screened for further relevant material, and an unstructured search of Google Scholar was performed for additional grey literature.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background: Depression is a leading cause of disability, burdened by high levels of non-response to conventional antidepressants. Novel therapeutic strategies targeting non-monoaminergic pathways are sorely needed. The widely available and safe statins have several putative mechanisms of action, especially anti-inflammatory, which make them ideal candidates for repurposing in the treatment of depression. A large number of articles has been published on this topic. The aim of this study is to assess this literature according to evidence-based medicine principles to inform clinical practise and research.Methods: We performed a systematic review of the electronic databases MEDLINE, CENTRAL, Web of Science, CINAHL, and ClinicalTrials.gov, and an unstructured Google Scholar and manual search, until the 9th of April 2021, for all types of clinical studies assessing the effects of statins in depression.Results: Seventy-two studies were retrieved that investigated the effects of statins on the risk of developing depression or on depressive symptoms in both depressed and non-depressed populations. Fifteen studies specifically addressed the effects of statins on inflammatory-related symptoms of anhedonia, psychomotor retardation, anxiety, and sleep disturbances in depression. Most studies suggested a positive effect of statins on the occurrence and severity of depression, with fewer studies showing no effect, while a minority indicated some negative effects.Limitations: We provide a narrative report on all the included studies but did not perform any quantitative analysis, which limits the strength of our conclusions.Conclusions: Robust evidence indicates that statins are unlikely to lead to depressive symptoms in the general population. Promising data suggest a potential role for statins in the treatment of depression. Further clinical studies are needed, especially in specific subgroups of patients identified by pre-treatment assessments of inflammatory and lipid profiles.

show abstract

Section: Resultsmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…There was a significant reduction in depressive symptoms in all three groups and no significant differences in the primary or secondary outcomes between groups. In a recent meta-analysis that pooled the results from the aforementioned studies, statins were more efficacious than placebo in addition to antidepressants to reduce depressive symptoms at 8 weeks (N = 255, SMD = −0.48, 95%CI: −0.74 to −0.22) and 12 weeks (N = 134, SMD = −0.47, 95%CI: −0.89 to −0.05); an exploratory network meta-analysis suggested that simvastatin, which is more lipophilic, may be more efficacious than the rosuvastatin, with is less lipophilic [ 48 ].…”

Section: Resultsmentioning

confidence: 99%

Targeting Metabolic Dysfunction for the Treatment of Mood Disorders: Review of the Evidence

Jones

Farooqui

Kloiber

et al. 2021

Life

View full text Add to dashboard Cite

Major depressive disorder (MDD) and bipolar disorder (BD) are often chronic with many patients not responding to available treatments. As these mood disorders are frequently associated with metabolic dysfunction, there has been increased interest in novel treatments that would target metabolic pathways. The objectives of this scoping review were to synthesize evidence on the impact on mood symptoms of lipid lowering agents and anti-diabetics drugs, while also reviewing current knowledge on the association between mood disorders and dyslipidemia or hyperglycemia. We propose that metabolic dysfunction is prevalent in both MDD and BD and it may contribute to the development of these disorders through a variety of pathophysiological processes including inflammation, brain structural changes, hormonal alterations, neurotransmitter disruptions, alteration on brain cholesterol, central insulin resistance, and changes in gut microbiota. Current evidence is conflicting on the use of statins, polyunsaturated fatty acids, thiazolidinediones, glucagon-like peptide agonists, metformin, or insulin for the treatment of MDD and BD. Given the paucity of high-quality randomized controlled trials, additional studies are needed before any of these medications can be repurposed in routine clinical practice. Future trials need to enrich patient recruitment, include evaluations of mechanism of action, and explore differential effects on specific symptom domains such as anhedonia, suicidality, and cognition.

show abstract

“…In the most recent meta-analysis of randomized clinical trials on 5 studies and 389 participants, De Giorgi et al reported significant benefits of add-on statins at 8 and 12 weeks of treatment. In comparing statins, simvastatin, the most lipophilic compound, demonstrated a stronger antidepressant capability than atorvastatin [ 62 ]. This was consistent with a previous study on the antidepressant effect of statin in post coronary artery bypass graft with mild-moderate clinical depression, demonstrating a greater efficacy of simvastatin over atorvastatin [ 63 ].…”

Section: Introductionmentioning

confidence: 99%

Lipophilic vs. hydrophilic statins and psychiatric hospitalizations and emergency room visits in US Veterans with schizophrenia and bipolar disorder

et al. 2021

View full text Add to dashboard Cite

Objective Psychiatric hospitalizations and emergency department (ED) visits are costly, stigmatizing, and often ineffective. Given the immune and kynurenine activation in bipolar disorder (BD) and schizophrenia, as well as the immune-modulatory effects of statins, we aimed to compare the relative risk (RRs) of psychiatric hospitalizations and ED visits between individuals prescribed lipophilic vs. hydrophilic statins vs. no statins. We hypothesized (a) reduced rates of hospitalization and ER utilization with statins versus no statins and (b) differences in outcomes between statins, as lipophilia increases the capability to penetrate the blood–brain barrier with potentially beneficial neuroimmune, antioxidant, neuroprotective, neurotrophic, and endothelial stabilizing effects, and, in contrast, potentially detrimental decreases in brain cholesterol concentrations leading to serotoninergic dysfunction, changes in membrane lipid composition, thus affecting ion channels and receptors. Methods We used VA service utilization data from October 1, 2010 to September 30, 2015. The RRs for psychiatric hospitalization and ED visits, were estimated using robust Poisson regression analyses. The number of individuals analyzed was 683,129. Results Individuals with schizophrenia and BD who received prescriptions for either lipophilic or hydrophilic statins had a lower RR of psychiatric hospitalization or ED visits relative to nonstatin controls. Hydrophilic statins were significantly associated with lower RRs of psychiatric hospitalization but not of ED visits, compared to lipophilic statins. Conclusion The reduction in psychiatric hospitalizations in statin users (vs. nonusers) should be interpreted cautiously, as it carries a high risk of confounding by indication. While the lower RR of psychiatric hospitalizations in hydrophilic statins relative to the lipophilic statins is relatively bias free, the finding bears replication in a specifically designed study. If replicated, important clinical implications for personalizing statin treatment in patients with mental illness, investigating add-on statins for improved therapeutic control, and mechanistic exploration for identifying new treatment targets are natural next steps.

show abstract

Statins for major depressive disorder: A systematic review and meta-analysis of randomized controlled trials

Cited by 32 publications

References 52 publications

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

Targeting Metabolic Dysfunction for the Treatment of Mood Disorders: Review of the Evidence

Lipophilic vs. hydrophilic statins and psychiatric hospitalizations and emergency room visits in US Veterans with schizophrenia and bipolar disorder

Contact Info

Product

Resources

About