FDA re-examining safety of new drug approved for Parkinson’s disease psychosis

By Dr. Ananya Mandal, MDApr 26 2018

The United States Food and Drug Administration (FDA) is looking again at the safety of a drug Nuplazid that was approved earlier in 2016. This is the only drug that has been approved for the treatment of psychiatric manifestations such as hallucinations and delusions that are associated with Parkinson's disease.

Parkinson's disease. 3D illustration showing neurons containing Lewy bodies small red spheres which are deposits of proteins accumulated in brain cells that cause their progressive degeneration. Image Credit: Kateryna Kon / Shutterstock

Last week at a budget hearing FDA Commissioner Scott Gottlieb while speaking to members of Congress announced that the agency would be taking another look at the safety of this new drug. There have been hundreds of deaths associated with this new drug after it was marketed. The reports of the deaths have been voluntarily provided by caregivers and medical health professionals. According to the agency, the investigation into the causative association of this new drug and the deaths began a few weeks ago.

When the safety concerns about a drug come to the forefront, the FDA generally looks at the previous safety data that have been submitted by the makers of the drug. After following up the reported cases of harm caused by the drug, the agency might change its blanket approval status. The drug may not always be banned but there may be restrictions to where it could be used and label changes and warnings may be added to protect users while benefit those truly in need. In rare cases the drug may be completely banned if it is deemed unsafe for human use. As of now the adverse events related to the drug have been reported and the agency is carrying out the safety evaluations. The drug is still on the market the agency said and physicians can prescribe it for use until further decisions have been made.

Till date the deaths reported in patients taking Nuplazid concomitantly along with other medications have been seen among the elderly with advanced stages of Parkinson’s disease. These patients are generally of poor health and are on numerous other medications as well. All of these factors could raise the risk of deaths.

Experts are sceptical about the use of this new drug that received FDA approval on an expedited basis. FDA had designated the drug as “breakthrough therapy” that showed “substantial improvement” in patients with a life threatening or serious illness. The expedited approval of the drug, believe experts, could have meant missing out on vital safety information.

Dr. Paul Andreason was a physician who headed the FDA medical review panel for Nuplazid. He had warned then that in the clinical trials, deaths were more common with the drug compared to those taking placebo instead. The FDA however had ruled that the benefits provided by the new drug outweigh the risks. There being no other safer alternatives, the drug was given a green light amidst the warnings. The families of the patients receiving the medications too reported significant improvement. The side effects with the drug included not only increased risk of deaths but also fatigue, nausea, insomnia, falls etc.

Within the first year of use, Nuplazid has been associated with nearly 700 deaths according to the FDA data. In nearly 1000 patients, the hallucinations persisted even when the patients took the drugs.

Acadia Pharmaceuticals, makers of the new drug, and the FDA have both agreed upon the complex safety profile of the drug and specific safety warnings are added on the labels. Acadia’s shares fell as a result of this issue.