Do Corticosteroids Like Prednisone Shrink the Brain?

Can cortisone-type drugs (corticosteroids, aka glucocorticoids) have a negative impact on the brain? That is an issue that was recently considered in an article published in BMJ Open, Aug. 30, 2022. The most prescribed corticosteroid is prednisone. Does prednisone shrink the brain? What about other corticosteroids, including those that are inhaled? The findings of the new study are somewhat disconcerting.

Does Prednisone Shrink the Brain?

Let’s cut to the chase.

The new study in BMJ Open concludes:

“This study shows that both systemic [oral or injected] and inhaled glucocorticoids are associated with an apparently widespread reduction in white matter integrity, which may in part underly the neuropsychiatric side effects observed in patients using glucocorticoids. Since these medications are widely used, awareness of these associations is necessary across medical specialties and research into alternative treatment options is warranted.”

This is not welcome news. Millions of people rely upon corticosteroids to treat a wide range of disorders. When I lost my hearing in one ear, the otolaryngologist prescribed high-dose methylprednisolone. It saved my hearing! Steroids are also used to treat severe allergic reactions, brain inflammation, asthma, COPD, autoimmune diseases, Addison’s disease and certain kinds of cancer. These drugs can be life savers! We believe that short-term use should not pose a significant risk.

But there is a dark side to steroids that you can read about at this link. And now we are learning that drugs like prednisone shrink the brain if they are taken in high doses for long periods of time.

What Does Brain Shrinkage Mean?

According to the Cleveland Clinic:

“People with brain atrophy, also called cerebral atrophy, lose brain cells (neurons), and connections between their brain cells and brain volume often decreases. This loss can lead to problems with thinking, memory and performing everyday tasks. The greater the loss, the more impairment someone has.”

As people age, they often experience some brain shrinkage. People who have an alcohol abuse problem are likely to have brain atrophy. Head injuries can also accelerate the process. We did not know that long-term use of corticosteroids might also have this effect.

The New Research Regarding Steroids and the Brain:

The authors of the new study point out that when patients have a tumor on the pituitary gland (Cushing disease), they may make excess amounts of glucocorticoids.

When that happens:

“…it has been established that long-term glucocorticoid excess is associated with global cerebral atrophy and decreased cortical thickness and grey matter volumes in specific brain regions…. Moreover, a few small studies have shown volumetric reductions in specific brain regions, including the hippocampus and amygdala, in patients using chronic and/or high-dose synthetic systemic glucocorticoids. Besides these structural abnormalities, several studies in animal models and patients with Cushing disease have also demonstrated widespread reductions in white matter integrity throughout the brain.”

Did Prednisone Shrink the Brain?

The new study in BMJ Open asks some intriguing questions. The authors recognized that high doses of corticosteroids may cause shrinkage of the brain, especially in important brain structures such as the hippocampus, amygdala and cerebellum. Such areas of the brain are important for “cognitive processes” and “emotional regulation.” But previous studies have been inconsistent.

These investigators used the UK Biobank database to analyze MRI images for 222 users of oral corticosteroids, 557 patients who relied upon inhaled corticosteroids and 24,106 controls who did not take such cortisone-like drugs.

They found that people who regularly took corticosteroids (both oral and inhaled) had decreased white matter integrity in the brain. This brain shrinkage may pose problems for people on long-term steroid therapy. The authors of the research point out that chronic exposure to such drugs may also increase the risk for depression, mania and cognitive impairment.

What Are the Implications of the New Study?

According to the authors:

“It is well known that exogenous [administered] glucocorticoids are associated with neuropsychiatric side effects, including not only potentially severe mood disturbances such as depression and mania, but also cognitive impairment such as concentration and memory problems. In this study, glucocorticoid users reported a higher frequency of several mental health complaints, while their cognitive performance was not significantly different, except for worse scores on the symbol digit substitution task in systemic glucocorticoid users.”

The researchers appropriately point out that the conditions for which such steroids are prescribed could also be contributing to neuropsychiatric symptoms. COPD, chronic asthma, rheumatoid arthritis and autoimmune disorders can all produce psychological side effects.

They go on to add, though:

“Nevertheless, awareness for the potential of glucocorticoids to affect the brain and cause neuropsychiatric symptoms is important, since these medications are prescribed for a wide range of conditions by many different medical specialties and are used by a substantial proportion of the population.”

Corticosteroids Have Been Extremely Popular!

Cortisone-like drugs have been on a roller coaster for decades. During the 1950s, both patients and doctors thought these medications were miracles.

A patient crippled with rheumatoid arthritis would often be in great pain and have difficulty walking. A doctor would prescribe cortisone, dexamethasone, prednisone or prednisolone. Not long afterwards, a patient would be walking again without a cane or crutches. They would be pleased to have less pain.

But relief came at a price. Patients on high doses of corticosteroids would often develop weight gain, diabetes, high blood pressure, cataracts, glaucoma, stomach ulcers, muscle weakness, irregular heart rhythms or osteoporosis. A rheumatologist we admire once told us that “corticosteroids melt bone.”

Once doctors realized that there was a dark side to cortisone-like drugs, they became much more cautious. Instead of prescribing high doses of such “steroids” for months or years, they prescribed NSAIDs (non-steroidal anti-inflammatory drugs). You are familiar with medications like diclofenac, ibuprofen, indomethacin, meloxicam, naproxen, piroxicam and sulindac. But they too have side effects. More about that at this link.

Corticosteroids Are BACK!

Although there is a realization that cortisone-like drugs (glucocorticoids) pose significant risks, they have become very popular once again. Doctors prescribe prednisone more often than ibuprofen. At last count, over 9 million people were taking this corticosteroid annually. Not far behind is fluticasone, a very popular inhaled steroid. And of course there are many other oral and inhaled steroids.

Let’s not forget injected glucocorticoids. Physicians administer steroid shots to ease pain in the back, knees, shoulders and hips. They perceive that such local injections do not produce systemic side effects. You can learn more about that concept at this link and here.

A Reader Question: Will Prednisone Shrink the Brain?

Q. After pulling weeds in my backyard last month, I came down with a terrible itchy, weeping red rash. The dermatologist diagnosed poison ivy and prescribed prednisone. The dose started high and dropped gradually over two weeks.

I was about halfway through the treatment when I read headlines that steroids change your brain structure. That’s got me a bit freaked out, to say the least. Prednisone is a steroid, isn’t it? How much does the brain change? Is this something I should worry about?

A. The recent research published in BMJ Open (Aug. 30, 2022) is disconcerting. But we don’t think you have much to worry about.

The scientists found that people who regularly took corticosteroids (both oral and inhaled) had decreased white matter integrity in the brain. This brain shrinkage may pose problems for people on long-term steroid therapy. The authors of the research point out that chronic exposure to such drugs may also increase the risk for depression, mania and cognitive impairment.

A short course of prednisone will provide dramatic relief from a severe allergic reaction. It might cause insomnia, but we assume that it should not produce lasting brain changes. You can learn more about the side effects of short term steroid use at this link.

Please share your own experience with corticosteroids like prednisone in the comment section below.