A compound that occurs naturally in the brain and other areas of the body may be a promising new treatment for the most severe and disruptive symptoms of schizophrenia.
A pilot study at the Durham, N.C., Veterans Affairs Medical Center, reported online on April 1 in the journal Neuropsychopharmacology, suggests that the neurosteroid pregnenolone lessens symptoms of schizophrenia for which no treatment options are available. The research was conducted by a multi-institutional team led by NARSAD Investigators Christine Marx, M.D., and Richard Keefe, Ph.D., of the Duke University Medical Center.
NARSAD Scientific Council member Jeffrey A. Lieberman, M.D., of Columbia University, one of the world’s leading experts on the psychopharmacology of schizophrenia, who participated in the research, stated:
“Drug development for mental health disorders has been moving at a glacial pace, and we are in desperate need of new and novel treatments. This small, proof of concept study represents a potentially major advance.”
Also participating in the study were NARSAD Investigator Adam Savitz of Weill Medical College, Cornell University, and collaborators from the University of Maryland and the University of North Carolina at Chapel Hill.
While antipsychotic medications can help reduce hallucinations and delusions associated with schizophrenia for some patients, the other two categories of symptoms often continue to significantly disable patients -- the so-called negative symptoms, such as apathy, lack of emotion and poor social functioning, and the cognitive symptoms, which include memory impairment and difficulty concentrating and completing tasks.
“If replicated through further research, pregnenolone could provide a novel treatment for the cognitive and negative symptoms in schizophrenia, which severely impact the daily lives of patients,” said Dr.Marx.
“Antipsychotic medications are the only FDA approved treatments for schizophrenia, but the effects are typically modest and do not address the fundamental core of the disorder,” added Dr. Keefe, Ph.D.
Prior research had found that pregnenolone enhanced learning and memory in rodents while also influencing the function of brain receptors associated with schizophrenia. Pregnenolone is present in varying levels in humans, but not much was known about how it was regulated.
The new study included 21 people with schizophrenia or schizoaffective disorder who took a placebo for two weeks and were then randomly assigned to take pregnenolone or placebo for eight weeks in conjunction with one of the antipsychotic medications aripiprazole, olanzapine, quetiapine or risperidone.
The results showed that patients taking pregnenolone had more than 20 percent improvement on a test used to calculate negative symptoms compared to the placebo group. Tests used to assess cognitive impairment also pointed to improvements in the pregnenolone group. Patients with the lowest natural levels of the neurosteroid reported the most significant improvements on memory and concentration tasks.
While pregnenolone is available as a dietary supplement, there have been extremely few studies of it. The pregnenolone used in the Durham study was carefully monitored to meet FDA standards for purity, unlike supplements available over the counter.
“Further research is needed among a larger cohort of patients to confirm the findings we observed, but we are encouraged because pregnenolone was well tolerated and improved symptoms that we have not traditionally been able to treat,” Dr. Keefe explained.
Researchers said that larger studies are planned to further investigate pregnenolone's effects on schizophrenia, in addition to pilot studies in other conditions such as traumatic brain injury and post-traumatic stress disorder.
(This article was adapted with permission from Duke University Medical Center.)