Negative findings on oxytocin in schizophrenia spur some to ‘move on’
EXPERT ANALYSIS AT THE ECNP CONGRESS
Dr. Neumann believes clinical studies also should first determine what a high level of oxytocin looks like in healthy people whose oxytocin systems have been stimulated vs. what constitutes a high level in those whose systems are impaired, such in those with schizophrenia. In her work with animals, Dr. Neumann said she has found that different kinds of stimulation, whether it be exercise, sex, or stress, lead to different levels of oxytocin released into the blood stream. These kinds of data from humans would help determine the right amount of the hormone necessary to establish a positive treatment effect. “This should be done more in laboratories, not just the taking of basal levels. Basal levels mean nothing.”
Deanna L. Kelly, Pharm.D., professor of psychiatry and the director of the treatment research program at the University of Maryland, Baltimore, also wonders about trial designs, albeit her more pressing concerns are how the study drug is administered and in what setting.
“I think it’s important for us as a field to make sure we’re delivering [oxytocin] appropriately,” Dr. Kelly said during a presentation at the meeting. She noted her theory that, of the single-dose challenge studies in schizophrenia that have shown an effect on social cognition, most were likely conducted under tight supervision to ensure the medication was “delivered properly.”
Dr. Kelly presented her own negative data from a study of 56 people, mostly men in their mid- to late 40s with schizophrenia or schizoaffective disorder, selected for their enduring negative symptoms. Participants were treated either in an in- or outpatient setting based on their normal treatment regimen and were randomly assigned to receive either placebo, oxytocin, or the acetylcholinesterase inhibitor galantamine.
Oxytocin, which was administered intranasally at 24 IU twice daily, was chosen for its effect on negative symptoms in schizophrenia. Galantamine – often used to treat impaired cognition in Alzheimer’s disease – was dosed orally at 12 mg twice daily and was intended to address cognitive deficits. After a 4-week lead-in phase and 6 weeks of double-blind treatment, neither of the study drugs was found superior to placebo when it came to improving either negative symptoms or cognitive processes.
Some differences were found between those in the in- and outpatient settings, although they were not significant. However, in a previous study, Dr. Kelly conducted with her colleagues, patients treated with intranasal oxytocin in the inpatient setting showed significant improvement vs. controls treated in the inpatient setting. However, they did not find an overall negative symptom effect, and no difference was found among those treated as outpatients (Schizophr Res. 2013 Apr;145[0]:110-5).
“It could be that these patients are more closely watched by the nursing staff, and they’re getting the six sprays twice daily into the nose, whereas the outpatients might not be spraying it correctly ... [so that] it gets into the brain,” Dr. Kelly said.
For his part, Dr. Weiser said his study might have been too short in duration with too few subjects who already were too far into their disease state. The 48 people in his 3-week study were typically male, 37 years old, and with an average age of disease onset of about 23 years. Positive and Negative Syndrome Scale (PANSS) scores were about 69 for the study group and 66 for the placebo group.
“Perhaps patients with more severe PANSS scores might show more improvement,” Dr. Weiser said in his presentation.
Regardless, unless a genetic breakthrough occurs that helps identify subgroups of people in whom oxytocin treatments would have a positive effect, Dr. Weiser thinks interest in oxytocin for schizophrenia should end.
“The field is thirsty for something that works for schizophrenia,” said Dr. Weiser in the interview. “But regardless of wonderful preclinical [findings] on oxytocin, if the bottom line is that when you give it to patients they don’t get better, then we need to figure out a different intervention to try.”
Not so fast, Dr. Neumann says. “We have to look more carefully. We can’t just take any patients, treat them with a huge, superficial dose and then think, ‘Oh, this will do something.’ We have to do better homework.”
Dr. Weiser’s and Dr. Kelly’s respective research is funded by the Stanley Medical Research Institute. Dr. Kelly is an adviser to Lundbeck and XOMA.
On Twitter @whitneymcknight
