05/31/2008- The active ingredient in the acne drug Accutane— known generically as isotretinoin—more than doubles the risk of depression, according to a recent study.  The study is the first controlled investigation to find a statistically significant link between Accutane and depression, Dr Anick Berard, from CHU Sainte-Justine Research Centre in Montreal, and colleagues, state in a report in the Journal of Clinical Psychiatry.  “Current guidelines should possibly be modified to include psychiatric assessments of patients prior to and during isotretinoin therapy,” the researchers wrote.

Berard’s team studied 30,496 people from Quebec, Canada, who received at least one Accutane or isotretinoin prescription from 1984 through 2003.  During the study period, 126 of these individuals received a depression-related diagnosis, hospitalization, or treatment.  Also, based on earlier research, the researchers focused on isotretinoin use in the five months prior to the depression diagnosis—the risk period—as compared with a five-month period a year before the diagnosis—the control period.  After accounting for potential factors that might influence the results, isotretinoin exposure was associated with a greater than 2.6-fold relative risk of depression, the team found.  “Because depression could have serious consequences, close monitoring of isotretinoin users is indicated,” Berard and colleagues concluded.

Suicide is common in the US, representing the fourth leading cause of death for those aged 18 to 65 and the third leading cause for those aged 15 to 24.  Add to those figures the complexity of medications.  And recently, reports have been filed with drug makers and the Food and Drug Administration (FDA) on at least six drugs or drug classes that may be linked to suicide or suicidal thoughts; the acne drug, Accutane, is among these.

Recently, the Food & Drug Administration (FDA) released notices about several such medications including Singlulair; epilepsy drugs including carbamazepine, gabapentin, felbamate, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, and valproate; and the smoking-cessation drug Chantix.  Reports have been filed on SSRI antidepressants including Paxil and Prozac, the influenza drug Tamiflu, and the acne medicine Accutane.   “The brain is a complex organ, and most of the drugs are complex as well,’’ says Dr. Thomas Laughren, head of the division of psychiatric products at the FDA.  “It’s not unreasonable to think that a drug that gets into the brain may have effects other than you hope they would.’’

Kelly Posner, principal investigator at the Center for Suicide Risk Assessment at Columbia University in New York, is working with the FDA to determine suicide risks and at-risk categories; Posner’s quantitative tools and questionnaires are being applied to drugs on the market and in testing.  “We know that whether or not these drugs actually cause suicidal thought or action is a question we have to answer, but up until now, none of the clinical trials for the drugs were set up to address the question,’’ says Posner.

Meanwhile, Congressman Bart Stupak (Democrat-Michigan) reported his teenage son B.J. killed himself in 1999 after several months on Accutane and said in 1998, the FDA publicly noted reports of depression, psychosis, and suicidal thoughts and actions with Accutane; in 1999 when B.J. was prescribed Accutane, their doctor did not inform them of the risk and the prescription’s patient information did not include it.