Retinoic Acid and Suicide

Retinoic acid is an organic compound derived from Vitamin A, that is involved in the development of the brain and in normal visual function. It is because of the involvement in the formation of the brain that medicine containing retinoic acid like compounds must not be given to women who could become pregnant.

In recent years it has become clear that it is also involved in the function of the mature nervous system, and there have been suggestions that it may have a role in illnesses life Alzheimer’s disease and schizophrenia.

One of the big breakthroughs in skin care was the introduction, in 1982, of a form of retinoic acid – isoretinoin – for the treatment of severe acne. It is marketed as Accutane in the USA and Roaccutane in the United Kingdom. Since its introduction there have been claims that it has caused depression and suicide in some patients taking it. The package insert specifically mentions this possible association. The trouble has been trying to sort out whether people taking it for acne became depressed because of the acne, whether it was the drug, or whether it was a chance association. 13 million patients have taken it world-wide, so sadly some depression might occur by chance.

That it was the drug causing the problem was supported by reports of people developing depression within days of starting the medicine. But it’s always difficult to go from association to causality. After all, it has not been possible to prove that smoking causes lung cancer, though nobody doubts it, becuase the association between the two is so strong.

The Medicines and Healthcare products Regulatory Agency had received 1,588 reports of suspected adverse events experienced by people taking the drug up to this month. This included 25 people who died from suicide.

Now a paper in the journal Neuropsychopharmacology has added substantial support the the notion that the medicine may cause depression. The researchers gave a form of retinoic acid to adolescent mice. They found that while there was no change in the physical abilities of the mice, the rodents spent significantly more time immobile in a range of laboratory assessments designed to test their response to stress.

This was interpreted as a sign that the animals were exhibiting signs of depression.

It’s difficult to extrapolate from mice to humans, and this certainly does not nail down the problem. It also does not mean that people should stop their treatment: this medicine works. But it emphasizes the importance of doing what the package insert says: watching young people with acne who are on treatment for any signs of depression.