Is There a Role for Statin Therapy in Psychiatry? – Professor Michael Berk

Posted on: May 26, 2020
Last Updated: December 12, 2023

Professor Michael Berk is an NHMRC Senior Principal Research Fellow and Alfred Deakin Chair of Psychiatry at Deakin University and Barwon Health, where he heads the IMPACT Strategic Research Centre. He holds an Honorary position at both Melbourne and Monash University and is a highly cited researcher with over 800 published papers predominantly in mood disorders. His major interests are in the discovery and implementation of novel therapies, and risk factors and prevention of psychiatric disorders.

Author Quotes 

It makes mechanistic sense that an anti-inflammatory should work in people with inflammation and not in people who don’t have inflammation…so the next generation of anti-inflammatory studies should stratify people for inflammation at baseline.

The next question is, if you have depressed people, if you give them statins could this possibly be useful?

Summary

Mechanism of action of statins:

  1. Competitive, reversible inhibition of HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis, preventing the endogenous production of cholesterol.
  2. The reduction in cholesterol concentration within hepatocytes triggers up-regulation of low-density lipoprotein (LDL)-receptor expression, which promotes the uptake of LDL and LDL-precursors from systemic circulation.

Possible neuropsychiatric effects of statins may be mediated by [McFarland A et al., 2014]

  • Immunomodulatory effects: e.g. reduction in ROS and matrix metalloproteinases (MMPs)
  • Modulate T-cell immunity
  • Enhanced differentiation of oligodendrocyte progenitor cells (OPCs) assisting in remyelination capacity
  • Reduction in neuroinflammation: e.g Reduced IL-6 and TNF-α
  • Reduction in oxidative stress including nitrite levels, lipid peroxidation, and restoration of reduced glutathione
  • Prevents the production of a number of intermediary molecules, including isoprenoid products such as farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP) associated with reduced cognitive function.
  • Enhance neurogenesis via increased vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) expression with reduced neuronal death in the hippocampus.
  • Reduced amyloid-β peptide (Aβ) production has implications for Alzheimer’s dementia
  • Reduction of NMDA related excitotoxic activity

Prof Berk starts off this presentation with a look at infliximab, a chimeric monoclonal antibody that binds to TNF-alpha, and its role in treatment-resistant depression.

Moving on, he discusses a couple of studies[Jialal I, et al. 2001, Ridker PM, et al. 2005] that investigated the effect of statins on inflammation.

He continues with a discussion of a small study that assessed the risk of developing depression in women on statins and shows an 80% risk reduction over time.[Pasco JA, et al. 2010] Replicated studies in men showed that the treatment also appeared to be preventive although data were not as robust.

He presents the results of a Ph.D. study into depression after a cardiac event where patients were followed up for 9 months. After 3 months, patients on statin therapy had a 69% reduction in the risk of developing depression which increased to 79% after 9 months.

A longitudinal study also showed that statin use was associated with a 38% decrease in the risk of depression, and evidence from meta-analysis now shows an overall reduction in risk in people taking statins.

Prof Berk presents results from a trial which revealed a statistical significance for lovastatin in the treatment of depression, and how statins and escitalopram have comparable efficacy in this area.

He concludes this video excerpt with a look at some studies into youth depression alleviation and potential targets for future treatments of psychiatric disorders.

Take-Home Points 

  • There is clinical evidence of a reduced risk of depression in people on statin therapy.
  • Statins + escitalopram combined therapy has a higher response than either alone.
  • Meta-analysis data show an overall effect of anti-inflammatory drugs in the treatment of depression.
  • Statins have not only been implicated in cholesterol-associated reductions in cognitive impairment but have also been found to reduce the odds of cognitive impairment independent of lipid levels
  • An additional meta-analysis in 2016 suggested that adjunctive treatment with statins could be useful for the treatment of depressive symptoms. [Salagre E et al., 2016]

Quiz


Learn more

  1. NAC and Mitochondrial Abnormalities By Professor Michael Berk
  2. Effect of the Mediterranean Diet On Depression By Prof Michael Berk
  3. Early Life Nutrition and Neurodevelopment By Prof Michael Berk
  4. The Role of the Gut Microbiome and Diet in Depression – Prof Michael Berk
  5. Healthy Diet vs Nutraceuticals in Depression By Prof Michael Berk
  6. Effect of Diet and Lifestyle Changes in Depression By Prof Michael Berk
  7. Applications of N-Acetylcysteine (NAC) – From Addiction to Autism By Prof Berk
  8. N-Acetylcysteine (NAC) in Schizophrenia and Bipolar Disorder- Prof Michael Berk
  9. Glutathione, Oxidative Stress and N-Acetylcysteine (NAC) in Psychiatric Disorders – Prof Michael Berk
  10. Oxidative and Inflammatory Biomarkers As Targets For Novel Therapies – Prof Michael Berk
  11. Cytokines and Inflammation By Professor Michael Berk

References

  1. Raison CL, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2013 Jan;70(1):31-41.
  2. Jialal I, et al. Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels. Circulation. 2001 Apr 17;103(15):1933-5.
  3. Ridker PM, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med. 2005 Jan 6;352(1):20-8.
  4. Pasco JA, et al. Clinical implications of the cytokine hypothesis of depression: the association between use of statins and aspirin and the risk of major depression. Psychother Psychosom. 2010;79(5):323-5.
  5. Stafford L, Berk M. The use of statins after a cardiac intervention is associated with reduced risk of subsequent depression: proof of concept for the inflammatory and oxidative hypotheses of depression? J Clin Psychiatry. 2011 Sep;72(9):1229-35.
  6. Otte C, et al. Statin use and risk of depression in patients with coronary heart disease: longitudinal data from the Heart and Soul Study. J Clin Psychiatry. 2012 May;73(5):610-5.
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