Isotretinoin and Depression Risk

It has long been suggested that the drug isotretinoin prescribed for hard-to-treat acne can cause depression. The product label itself warns that the drug (sold under the brand names Accutane, Absorica, Zenatane, and others) may cause "depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors."

Although these side effects are considered rare, a growing number of experts (including the American Academy of Dermatology) question whether there is any true connection between this effective oral acne drug and depression.

This article takes a look at the risk of depression in people who take isotretinoin to help you make an informed choice if your dermatologist recommends treatment.

Association Between Isotretinoin and Depression

Isotretinoin is an oral medication used to treat severe acne. While effective, the actual mechanism of action of the drug is poorly understood.

Isotretinoin is known to cause severe side effects in some people. Among them, people who are pregnant or breastfeeding cannot take isotretinoin due to the high risk of birth defects, including severe skull, eye, ear, mouth, brain, heart, and facial abnormalities.

In addition, isotretinoin can cause neurological (nervous-system-related) side effects ranging from headache, dizziness, and nervousness to fainting, seizures, and strokes.

There are some who suggested that the neurological side effects of isotretinoin may account for isolated reports of depression among users of the drug.

Among other things, isotretinoin is known to cross the blood-brain barrier that separates the brain from the rest of the body, Some studies have shown that it can inhibit (block) nerves that respond to mood-related hormones like serotonin and dopamine.

Because the lack of serotonin and dopamine is linked to depression, scientists initially concluded that this inhibitory action was the cause of depression in the small number of people who reported this side effect. However, current evidence is challenging that idea.

What the Current Research Says

Historically, studies have suggested that anywhere from 1% to 11% of people taking isotretinoin experience symptoms of depression (including chronic sadness, fatigue, sleep problems, and the lack of interest in things that usually bring them pleasure).

Despite some statistical evidence of a link, a growing number of experts question whether isotretinoin actually causes depression. There is no clear pattern as to who is affected and no definite proof that isotretinoin can block the effects of serotonin or dopamine in a qualitative way.

A 2019 study from Northwestern University Feinberg School of Medicine aimed to evaluate the risk based on the review of the medical records of 38,000 people with acne in the United States. Of the 1,087 people treated with isotretinoin, only 3.77% developed depression. This was a far lower rate of depression than people with acne who were not treated with isotretinoin (4.81%).

Similar findings were reached in a 2019 review of studies from China in which three of the 20 studies suggested that isotretinoin caused depression, while 17 of the 20 studies suggested that isotretinoin improved depression symptoms.

Prescribing Isotretinoin in People With Depression

It is unclear if isotretinoin has the potential to worsen depression in people already diagnosed with the disease. Even so, some researchers suggest that isotretinoin may not be the actual cause of depression.

If you are prescribed isotretinoin, it is usually because your acne is severe. It is well documented that the emotional impact of acne—on your self-image and self-esteem—can give rise to depression as an independent risk factor. On top of this, if isotretinoin doesn't work as well as a person hopes, their depression can deepen.

Studies also suggest that a great many people who reported depression after taking isotretinoin had pre-existing conditions that placed them at risk, including substance abuse, bipolar disorder, or a family history of depression.

On the Accutane product label, the U.S. Food and Drug Administration (FDA) states that "No one knows if (isotretinoin) caused these behaviors or if they would have happened even if the person did not take (isotretinoin)." 

As a precaution, the FDA still advises consumers to be aware of the potential for depression. Those who have depression should speak with their healthcare providers to fully understand the potential benefits and risks of treatment so that they can make an informed judgment.

How to Use Isotretinoin Safely

Although isotretinoin comes with side effects, the drug can be very effective at clearing severe nodular or cystic acne, Getting your condition under control not only reduces your chance of scarring but may also improve your self-image and mood.

While the risk of depression appears to be low, it is important to contact your healthcare provider if you or your child develop the following while on isotretinoin:

• Changes in mood and behavior
• Feeling unusually sad, angry, irritable, or aggressive
• Trouble concentrating
• Suicidal thoughts or thoughts of hurting yourself
• Seeing or hearing things that are not real

Even if these symptoms are not caused by isotretinoin, they are serious and need immediate treatment by a licensed medical practitioner.