How a cardiovascular disease drug could treat mood disorders

There are many tried-and-tested drugs used to treat the world’s most common health conditions and diseases, but what if some of those drugs could be repurposed to treat an entirely different health problem?

IMPACT’s Clinical Trials and Interventions theme investigates just that. The theme’s research projects partly focus on trialing the repurposing existing pharmacological agents and exploring how to put such treatments into practice.

One class of drugs that seem promising for repurposing is statins. Recently IMPACT researchers produced the narrative review, Statins: Neurobiological underpinnings and mechanisms in mood disorders. The review was designed to evaluate existing evidence for the novel use of statins, a widely prescribed type of cardiovascular disease drug, in the treatment of mood disorders and evaluate how that could be put into action.

“Statins’ primary medical use is in preventing and treating cardiovascular disease via their cholesterol-lowering effects,” said Dr Adam Walker, who prepared the review alongside co-first author Dr Yen Kim, under the guidance of Prof Michael Berk.

“However, separate to these effects, statins have a variety of additional ‘pleiotropic’ properties, or more mechanisms of action, that may be relevant for the treatment of mood disorder pathophysiology.”

And the existing evidence compiled for the review shows plenty of promise.

Why should we repurpose drugs?

According to Dr Walker, who is the current Trisno Family Fellow at Deakin University, the investigation of novel therapies and repurposing of existing treatments remains an underutilised area of research, particularly where drug safety profiles and interactions are well understood. This is especially the case in widely prescribed drugs such as statins.  

“Pleiotropic properties of statins have been under investigation for some time in adjacent disciplines of medicine, but few investigations have discussed these effects in their potential application to mood disorders such as depression,” Dr Walker said.

“This is one of the first reviews to consider possible neurobiological mechanisms in any depth.”

Mood disorders can be challenging to treat effectively. For example, in the case of Major Depressive Disorder about 30 per cent of people are considered resistant to conventional treatments, and many will only partially respond.

“Currently available treatments for mood disorders are useful, but there are shortfalls in treatment response,”

Dr Adam Walker

“There is a need to address these shortfalls, to optimise outcomes for patients that may not otherwise fully respond to primary treatments. ‘Adjunctive’ or add-on treatments may be of use for this purpose.

“The end goal is of course to eventually improve outcomes for patients suffering with mood disorders.”

How statins could help

Dr Walker says, mood disorders such as depression are thought to feature disturbances in lipid metabolism, oxidative stress and inflammation.

“Importantly the pleiotropic effects of statins include anti-inflammatory and anti-oxidative action, and preliminary evidence suggests that they may be of potential benefit in treating depression in at least some individuals,” he said.

“In the context of mood disorders (which often co-occur with other medical conditions) statins may be most beneficial as an adjunctive treatment in people with known cardiovascular risk factors.”

Dr Walker said early reports suggested statins may have negative impacts on mood, however more recent and rigorous research suggest that the opposite may be true, and they may have beneficial effects for some people diagnosed with mood disorders.

“This review supports further investigation of statins for this purpose,” he said.

Where to now? 

Dr Walker said as a review the impacts of this paper were predominantly academic, however it has contributed to knowledge gain, and the directions for future clinical research.

“Collectively, the evidence suggests statins may have potential as adjunctive agents for the treatment of mood disorders, however, as discussed in our review, many unknowns remain,” he said.“Not all statins were created equal—it is unclear which type of statin is best suited for this purpose, the appropriate dose that should be prescribed, or who might respond best to adjunctive statin treatment.

“High-quality evidence in the form of large-scale clinical trials in conjunction with considered biological investigations are needed if the potential clinical effects of statins on mood disorders is to be properly evaluated.” 

Dr Walker said the trials would need to be placebo-controlled, have multiple sites, and focus on evaluating perhaps one or two of the more promising adjunctive agents with pleiotropic properties. 

“The recently announced Mental Health Australia General Clinical Trial Network (MAGNET) being led by Prof Michael Berk is the perfect conduit for this, and as I understand it, there is a planned trial for statins in the pipeline,” 

Dr Adam Walker

MAGNET, which will be led by Deakin University, will bring more than 100 of Australia’s lead research institutions, health services and lived experience experts to develop new mental health treatments. It gained $12 million support from the Federal Government’s Medical Research Future Fund (MRFF) earlier this year.

To find the complete narrative review, click here.