Prednisone was synthesized in the mid-1950s by Arthur Nobile and has since been a miracle and a misery for people with autoimmune and inflammatory disease.

When I first started taking prednisone in 2011, I had no idea what I was in for and it showed. I gained about 10 pounds pretty quickly, “moon face” and all. When my brother came to visit he told me he barely recognized me. I had terrible acne that covered my chest and neck. My knees ached so badly I couldn’t stay in bed, and since I couldn’t sleep anyway, I was up early and late. I was completely miserable.

I was on 40-60 milligrams (mg) at the time, which is a lot.  A dose above 40 mg is considered a “high dose,” while anything below 7.5 mg is considered a “low dose” and to be “steroid sparing” (most patients don’t experience the side effects known to be associated with prednisone at this level) (https://www.aocd.org/page/SteroidsOral).

The prednisone did its job; my uveitis was brought to a screeching halt. But I couldn’t stay on the high dosage forever (thankfully) due to all of the side effects. I transitioned to combinations of prednisone and methotrexate and cyclosporine, eventually turning to RETISERT (see Treatments page).

I’ve been on and off prednisone since then, more time on than off, but at a much lower dosage. Typically I’ve been on 5-10 mg with pulses when I have a flare. And, I can honestly say, it’s often the only thing that keeps my uveitis at bay. That’s why prednisone is prescribed so regularly for a myriad of different conditions; it works and it works fast. Although the side effects of prednisone at high doses are likely unavoidable, I now am aware of them, long and short term, and what I can do to lessen them.

Let’s start at the beginning. 

What is prednisone and what does it do?

Prednisone is a synthetic glucosteroid. It is a type of corticosteroid that is closely related to and mimics cortisol, which is a hormone naturally produced by the adrenal gland in the body. 

When the body becomes stressed, the pituitary gland at the base of the brain releases ACTH (adrenocorticotropic hormone), which stimulates the adrenal glands to produce cortisol.

The extra cortisol allows the body to cope with stressful situations, such as infection, trauma, surgery, or emotional problems. When the stressful situation ends, adrenal hormone production returns to normal. 

The adrenal glands usually produce about 20 mg of cortisol per day, mostly in the morning, but they can produce five times that much when needed in a stressful (or perceived to be stressful) situation. Prednisone, the most commonly prescribed synthetic corticosteroid, is four to five times as potent as cortisol. Therefore, roughly 5 mg of prednisone is equivalent to the body’s daily output of cortisol. There are other synthetic corticosteroids available which differ in potency and half-life (Eustice, 2020).

During a stressful scenario your body is in “fight or flight” mode and thinks of little other than dealing with the stressor. Therefore, when you have increased corticosteroids in the body, your body blocks substances that create inflammatory actions called prostaglandins (which initiate healing and deal with allergic reactions) and white blood cells (which destroy foreign cells and allow the immune system to function properly). In this way, corticosteroids suppress the immune system.

Cortisol also helps to control the salt and water balance in the body as well as regulates carbohydrate, fat, and protein metabolism. When you have a heightened amount of corticosteroid in your body, this system too is thrown out of whack. And thus, we have side effects. 

Side Effects of prednisone

There are known side effects of prednisone, particularly with prolonged use, for virtually every system in the body. I’ve summarized some of the more common side effects below. Check out Drugs.com for a more complete list and more details.

When reading through some of these, it’s clear that many are connected and all are impacted by daily actions such as diet, exercise, stress response and sleep.

Adrenocortical Insufficiency

When given in a stronger dose than the amount the body can produce on its own, for prolonged periods, glucocorticoids may cause decreased secretion of endogenous (self-made) corticosteroids by suppressing pituitary release of corticotropin (secondary adrenocortical insufficiency). Basically, since you’re taking prednisone, the body senses the level of steroid is “high enough” and stops making as much. This is why it is dangerous to stop taking prednisone cold turkey (I’ll post about tapering off prednisone next month). The degree and duration of adrenocortical insufficiency is highly variable among patients and depends on the dose, frequency and time of administration, and duration of therapy. Talk to your doctor about adrenal supplements and lifestyle changes if you are feeling sluggish and tired all of the time (especially on high doses of prednisone). 

Immunosuppression and Increased Susceptibility to Infection

Increased susceptibility to infections is common on prednisone. It’s easier to get sick when the immune system is suppressed. This can mean anything from serious and potentially fatal infections like chicken pox and measles to persistent athlete’s foot and candida. Read Study Warns about higher infection Risk.

Remember that administration of live virus vaccines, including smallpox, is contraindicated (advised against) in patients receiving an immunosuppressive dosage of glucocorticoids. Glucocorticoids, especially in large doses, increase susceptibility to and mask symptoms of infection.

Infections with any pathogen, including viral, bacterial,or fungal infections in any organ system, may be associated with glucocorticoids. There are a variety of ways to get rid of or lessen the severity of infections such as fungal infections, both with and without medication. In my experience, diligence is paramount if you are going to be on prednisone for a while. 

Musculoskeletal Effects

Muscle wasting, muscle pain or weakness, and atrophy of the protein matrix of the bone resulting in osteoporosis or osteopenia can all be side effects of prednisone. Osteoporosis and related fractures are one of the most serious adverse effects of long-term glucocorticoid therapy. The American College of Rheumatology (ACR) currently considers patients receiving or planning to receive greater than 2.5 mg of prednisone daily for three months or longer to be at risk for bone loss (Glucocorticoid-Induced Osteoporosis).

A high protein diet may help to prevent adverse effects associated with protein catabolism. Calcium and vitamin D supplementation and weight-bearing exercise that maintains muscle mass are suitable first-line therapies aimed at reducing the risk of adverse bone effects.

I had a Dexascan in 2018 which showed slight osteopenia in my hips. It surprised me because I’ve always been pretty active and wasn’t on a high dose of prednisone at the time (I was nursing my second son at the time which may have contributed). I’ve since increased my calcium and vitamin D and my weight lifting. My insurance covers another scan this December, so we will see if it worked!

I also remember when I was on 60 mg, the pain in my lower back and knees was so bad I would wake up at night and not be able to sleep. 

Ocular Effects

As many of us with uveitis know, the treatments often involve the side effect of cataracts and increased intraocular pressure. Prolonged use of prednisone may result in posterior subcapsular and nuclear cataracts  and/or increased intraocular pressure (IOP) which may result in glaucoma or may damage the optic nerve if left unchecked. 

Nervous System Effects

Side effects of prednisone include insomnia, mood swings, and depression. I tend more toward the “intense” side of personalities at times (hey, I’m a Scoprio.. what can I say?!) and when I’m on higher doses of prednisone I have to consciously remind myself to tone it down a little. Especially when I haven’t slept much due to high doses; I usually notice trouble sleeping when I’m on 20 mg or more. Another side effect I’ve noticed, but don’t generally read in the literature is feeling warm all of the time, which can also impact mood and sleeping. Altering your sleep schedule (can you fit in a nap?) based on when you sleep best can help as well as just giving yourself down time and plenty of grace… and space.. from other people (sort of kidding). 

Endocrine and Metabolic Effects 

Prednisone may decrease glucose tolerance, produce hyperglycemia (high levels of sugar in the blood), and aggravate or precipitate diabetes mellitus, especially in predisposed patients. If glucocorticoid therapy is required in patients with diabetes mellitus, it may be necessary to change insulin or oral antidiabetic agent dosage or diet. Read What is the link between prednisone and diabetes?

The increased requirement for insulin, accompanied by potassium loss, sodium (and fluid) retention and increased appetite often lead to weight gain when uncontrolled. Monitoring carbohydrate and refined sugar, and sodium intake can help with these side effects. See the Prednisone Friendly Diet from Stop Sarcoidosis and Prednisone Weight Gain by Dr. Megan, Prednisone Pharmacist, who has really great info on her site.

Patients with hypothyroidism may have an exaggerated response to glucocorticoids. Glucocorticoids can lower serum TSH levels and decrease TSH secretion through direct effects on TRH in the hypothalamus. Chronic use of high dose glucocorticoids do not appear to cause clinically significant central hypothyroidism (Haugen, 2009).

Sodium retention with resultant swelling, potassium loss, and elevation of blood pressure may occur, but is less common with prednisone. Along with swelling is the less-than-fun phenomenon known as “moon face.” Read Embrace Moon Face and supplement potassium.

Dermatologic Effects

I’ve always struggled with acne, but let me tell you that prednisone acne is real. When I was on 60 mg, I literally bought turtle necks and wore them all the time because my neck and chest were so broken out (luckily it was winter). Prednisone impairs wound healing (remember, it’s telling your immune system to chill out) which can make acne last longer. 

Prednisone also thins out the skin which can cause you to bruise more easily (Bruising for No Reason? It Could Be Due to These Medications). 

So there you have the (abbreviated) long list of side effects of the miracle drug that is prednisone.

Next month I’ll talk about interactions, tapering and withdrawal, touch on pregnancy on prednisone, and COVID-19 risks on prednisone.