The Life Cycle of a Drug: Risperdal (risperidone)

In 1993 the FDA approved a second generation antipsychotic, risperidone, for treatment of schizophrenia in adults. Later two new indications were approved: (1) short-term treatment of acute manic or mixed episodes of bipolar I disorder in adults, and (2) treatment of irritability associated with autistic disorders in 5-16-year-old children. In 2007 two more new indications were short-term treatment of (1) 13-17-year-old schizophrenics and (2) manic or mixed episodes of bipolar I disorder in 10-17-year-olds. Johnson and Johnson's Janssen unit has been contesting, settling and occasionally winning cases across the US because the company illegally promoted off-label use of the drug. The whistle blower in this case was Allen Jones, a former investigator in Pennsylvania's Office of the Inspector General. In the video he speaks of a similar national program, TeenScreen.

In Texas, Johnson and Johnson created and funded the Texas Medication Algorithm Project, which was imported into Mr. Jones' jurisdiction as PennMAP. In 1996, the TMAP Project Director was John Rush, M.D. Steven Shon, M.D., the Medical Director of the Texas Mental Health and Mental Retardation Department, was one of three co-directors. After the first week of the trial, J&J settled the case for $158 million dollars after Dr. Shon's testimony made clear his and the company's culpability. This despite the fact that Dr. Shon's testimony exhibits no evidence that he considers himself culpable. Alison Bass links to an expert report prepared for the Texas Attorney General by Dr. David Rothman. Her post emphasizes J&J's ghostwriting campaign, which included a ghost-written article in the prestigious New England Journal of Medicine, and others.

In 2011, The Agency for Healthcare Research and Quality updated it's 2007 report on the efficacy of various off-label uses of risperidone and other second generation antipsychotics, here called atypical antipsychotics. A more readable version of Table A below may be found on their website. Some evidence, with many caveats, was found that risperidone might be helpful at some dose for some patients in six off-label uses. One of the uses, augmentation of the effectiveness of antidepressants for major depressive disorder, is unsurprising given that three other second generation antipsychotics have already been approved for this indication. There were many safety issues, including increased risk of death in the elderly suffering from dementia. The risk of weight gain and type 2 diabetes is also well known. Adverse effects on the motor nerves, called tardive dyskinesia, are a second reason not to use risperidone long-term. The complete report is available as a PDF.




What actually happened is Texas and elsewhere is that risperidone was prescribed with the goal of corporate and personal profits rather than the health of young and old Texans.

The Life Cycle of a Drug: New Formulation

Referring back to the bar graph in my original post for this series, the next industry strategy to be addressed is extension of the life cycle of a drug by production of a new formulation. Nucynta was approved in 2008 and Nucynta ER [extended release] is the new formulation just approved. There are people in chronic pain who are best served by an opioid narcotic analgesic that can be taken once daily.

Some controversy attends this approval because previous members of this class of very addictive drugs have been abused by crushing them so that immediate uptake of a large dose becomes possible. Nucynta ER has been formulated to make this kind of abuse more difficult.

J&J Gets FDA Approval Of Potentially Addictive Opioid Nucynta

Nucynta ER Approved For Moderate To Severe Chronic Pain Control