The U.S. Food and Drug Administration (FDA) approved Accutane (isotretinoin) in 1982. The drug manufactured by Roche treats severe acne in people older than 12, and teenagers are its primary users. Treatment can last up to six months and may be repeated if acne returns.
Doctors prescribe Accutane when other acne treatments fail. Because serious cases of acne can be such a physical and social burden, patients may be willing to tolerate some of the common side effects that come with Accutane use, including dry skin, headaches and cold-like symptoms.
Unfortunately, studies link Accutane to a series of serious side effects, including bowel diseases like Crohn’s disease, liver damage, depression, and miscarriage and birth defects if taken during pregnancy. In fact, women of childbearing age are required to enroll in a special pregnancy prevention program before beginning Accutane treatment.
Because of these side effects, more than 7,000 lawsuits have been filed against Roche Pharmaceuticals. Roche stopped making Accutane in 2009, but generic versions of Accutane, known as isotretinoin, are still available.
About half of Accutane users are women of childbearing age, making birth defects associated with Accutane use a significant concern. As of 2002 — the year generic Accutane was approved — the FDA had received reports of 172 babies born with a congenital defect or anomaly after maternal use of Accutane. From 1982 to 2006, more than 2,000 isotretinoin users became pregnant, resulting in many spontaneous or elective abortions.
Pregnancy prevention programs initiated by Roche seek to educate patients about taking measures to ensure that women of childbearing age do not become pregnant while taking Accutane and that they are aware of the risk of birth defects. However, these programs do not completely eliminate the occurrences of birth defects from Accutane. Roche has used the SMART program and the iPLEDGE program.
The SMART program required patients to sign consent forms, watch informational videos, take a pregnancy test and use two forms of birth control. The FDA did not deem the program effective, so in 2006 iPLEDGE was developed. This program required pregnancy tests from doctor’s offices and patient registration by computer.
A study completed in 2011 on Kaiser Permanente, California health care patients revealed that iPLEDGE did not significantly decrease fetal exposure to Accutane. The rate of fetal exposure was similar with both programs — an average three exposures for every 1,000 patients. The type of fetal danger resulting from exposure to Accutane is alarming, ranging from causing miscarriages to babies born with slits where ears should be.
Since 1985, Accutane has carried a black-box warning, the FDA’s most serious warning, detailing birth defect risks. The warning states: “Accutane must not be used by female patients who are or may become pregnant. There is an extremely high risk that severe birth defects will result if pregnancy occurs while taking Accutane in any amount.”
The boxed warning also lists possible birth defects that could result from taking Accutane, including:
- Skull abnormalities
- Ear abnormalities
- Facial dysmorphia
- Cleft palate
- Eye abnormalities
- Central nervous system abnormalities
- Thymus gland abnormality
- Cardiovascular abnormality
- Parathyroid hormone deficiency
- Lower IQ
Gastrointestinal disorders may cause inflamed and damaged intestines. Symptoms may come and go intermittently. Treatments vary based on the severity of symptoms and range from medication to bowel removal. Studies link Accutane to two types of gastrointestinal disorders: Crohn’s disease and ulcerative colitis. Crohn’s and ulcerative colitis manifest themselves differently and affect different parts of the intestinal tract.
They share some symptoms:
- Weight loss
- Abdominal pain
- Rectal bleeding
- Bloody diarrhea
The number of cases of gastrointestinal disorders associated with Accutane use has continued to grow over the years. From 1997 to 2002, there were 85 cases of Inflammatory Bowel Disease (IBD) associated with isotretinoin use, but the exact connection was not confirmed. In 1999, The American Journal of Gastroenterology published a letter to the editor asserting a possible connection between isotretinoin and IBD. Another study published in the same journal in 2005 reviewed 85 cases of IBD and found that Accutane was a possible trigger for the disease. From 2003 to 2011, the FDA adverse event database received reports of 266 cases of IBD associated with isotretinoin use.
Accutane and Crohn’s Disease
Roche periodically reviewed adverse drug reaction reports received through its call center. One of these, called the Internal Causality Assessment, issued on Jan. 6, 1994, noted that Accutane users experienced 104 cases of colitis syndromes, including Crohn’s disease. Researchers analyzed all adverse drug reaction reports submitted to the FDA between 1997 and 2002 and found 85 cases of Inflammatory Bowel Disease, including cases of Crohn’s disease, associated with Accutane use. Of those 85 cases, researchers found that isotretinoin use was highly probable as the cause in four cases, probably the cause in 58 cases and possibly the cause in 23 cases.
Dr. R. Balfour Sartor, Professor of Medicine, Immunology & Microbiology at the University of North Carolina at Chapel Hill and chief medical adviser to the Crohn’s & Colitis Foundation of America, says that more research into the link between Accutane and Crohn’s disease is needed. He also added that Accutane is generally prescribed to patients ranging in age from mid-teens to mid-30s — a population that is more prone to developing Crohn’s disease in the first place.
Crohn's disease can affect the small intestine, the large intestine or both:
- 30 percent of cases involve only the small intestine.
- 30 percent of cases involve only the large intestine.
- 40 percent of cases involve both intestines.
The most common symptoms of Crohn's disease are:
- Low-grade fever
- Weight loss
- Prolonged diarrhea
- Abdominal pain
Crohn's patients may also experience symptoms of possible bowel obstruction, such as:
- Bloating after eating
- Loud rumbling or gurgling noises coming from the stomach
Once the bowel has narrowed permanently, the patient may first experience some constipation, and eventually the constipation will become persistent. This can be caused by undigested foods becoming impacted in the bowel.
Ulcerative Colitis (UC) often starts in the rectal area and progresses to the colon. The lining of the colon can become inflamed and develop ulcers that produce pus or mucous. Around half of people with UC experience milder symptoms, such as abdominal pain, blood and pus in stools, diarrhea, fever, rectal pain and weight loss. People with severe cases of UC often require hospitalization for acute attacks. Repeated attacks cause thickening of the intestinal wall and rectum from scar tissue, which can cause infections. Complications from UC include blood clots, colorectal cancer, massive bleeding, tears in the colon, liver disease, mouth sores and ulcers. The only cure is a removal of the colon.
Inflamed lining of the colon due to Ulcerative Colitis
Some Accutane users have suffered from irreversible liver damage, which can lead to cirrhosis and require a liver transplant — a serious surgery that can be life-threatening. Due to this danger, liver enzyme tests are required prior to beginning Accutane and four weeks after treatment begins. Patients with a history of liver disease should not take this medication.
Additionally, alcohol should be avoided during treatment to decrease the risk of liver damage. In addition to patient reports of liver damage, studies have documented a connection between Accutane and liver damage. In Roche’s clinical trials, 15 percent of patients treated with Accutane experienced inflammation of or damage to liver cells.
In 2006, a research team at the University of California found that 11 percent of 13,772 Accutane patients tested had elevated liver enzymes. When enzymes are elevated, it can indicate inflammation or that triglycerides and fats have accumulated in the liver or that liver cells have died.
Symptoms of liver damage include:
- Upper abdominal discomfort
- Fluid buildup in the abdomen
- Swelling of the liver
- Jaundice (yellow color in the skin)
Depression and Suicide
Studies also linked Accutane to psychiatric disorders. From 1982 to May 2000, the FDA received hundreds of reports linking isotretinoin use to depression, including 37 suicides, 110 hospitalizations for depression or suicidal behavior, and 284 cases of non-hospitalized depression.
Roche responded to the reports of depression and suicide in 1998 by adding a warning to the medication’s label stating that Accutane could cause psychiatric disorders.
According to a study in the book Drug Injury: Liability, Analysis and Prevention, Drs. Donald Marks and Tzarina Middlekoop found that the number of formal adverse reaction reports, from national and international health agencies, of suicide and suicidal behavior associated with Accutane use reached 500, making it the fourth-highest number of adverse reactions in the United States prior to 2005.
Researchers don’t understand how Accutane causes psychiatric events, and a link between depression and Accutane has not been proven. However, the high number of reports of depression in people without a psychiatric history may suggest a link.
Symptoms of depression to be aware of include:
- Crying spells
- Loss of interest in activities
- Changes in appetite
- Difficulty concentrating
- Difficulty sleeping
- Poor performance at work or school
- Withdrawal from friends or family
- Feelings of worthlessness
- Acting on dangerous thoughts
- Thoughts about hurting or killing oneself