Here are some of the arguments that have been made by
Roche Pharmaceuticals and some dermatologists
in favor of their claims that there is no
relationship between Accutane and depression, and my response
to these arguments.

1. Suicide is very common in teenagers, to whom Accutane is most commonly given.

Suicide is half as common in teenagers as it is in people in their 20s.
The only age group with less suicide is toddlers.

2. Accutane is an acne drug. How could it cause depression?

Accutane is the brand name for isotretinoin, a compound that occurs
naturally in the body and is a member of the family of retinoids.
Retinoids bind to receptors in the brain and have neurological effects.
The skin and the brain come from the same place in development, the
ectoderm. The fact that it acts on the brain provides a biologically
plausible mechanism by which it can cause depression (one of the
factors used by pharmacoepidemiologists to establish causation).

Vitamin A is another retinoid known to cause psychosis,
depression, and other behavioral changes. The fact that a compound
in the same class has similar effects is further evidence of a causal relationship.

3. Scattered reports of depression do not prove that accutane causes
depression. There is no epidemiological evidence that Accutane causes

Challenge-rechallenge studies, where patients get depressed on the
drug, get better when they go off, and get worse again when they take it again,
are considered evidence of a causal relationship in the field of

4. There are no controlled clinical trials showing that
Accutane causes depression.

Controlled clinical trials are not required to show that a drug
causes a particular side effect. Case in point, no study has
shown that high dose steroids can cause behavioral changes, and yet that is
a known side effect of those drugs. The manufacturer of medications
should conduct studies as part of post-drug surveillance. In 2000 the FDA
was discussing such a study with the manufacturer but the study was
never conducted.

5. I don't see depression with Accutane in my patients. You can
develop depression with any drug, or cheerios or toothpaste. If it exists
it is sporadic or rare.

Physicians should not base their decisions based on their 'clinical experience.'
The literature supports an association based on established criteria that
are used to assess causality for drug side effects. A side effect
may be seen in a minority of patients, but still exist and be causally
related to the drug.

6. The manufacturer says they see no evidence of a causal relationship.

Then why do they list depression as a possible side effect of the drug?

7. Depression is very common. You can't say that the cases of depression
on Accutane didn't just occur by chance.

About 16% of people will develop depression at some time in their lives. However
only about 1% will develop it during a four month period. Accutane studies
show a rate of about 4-6%, which is higher.

8. The Bremner 2005 study did not show that Accutane caused depression.

The study wasn't designed to do that. It was designed to look at the effects
on brain function. Since only about 3% of people develop depression on Accutane,
a study of 28 people wouldn't be able to show that.

9. Accutane is a great drug for acne; it would be a pity to
take it off the market.

The fact that it works for acne does not obviate the responsibility
of physicians to warn about the possibility of depression and
monitor for symptoms. People with a history of depression need
to be monitored by a psychiatrist if they take Accutane.