For example, in the UCSD study, oxytocin treatment was associated with significant improvement, compared with placebo, on California Verbal Learning Test scores on total recall, short-delay free recall, short-delay cued recall, total repetitions, and total recall discriminability.
In the UNC study, oxytocin treatment was associated with significant improvement in accurate identification of third-order false belief in the Brüne Theory of Mind Test (an evaluation of the ability to understand others’ thoughts and feelings). There also was a trend toward more accurate identification of second-order false belief and deception, and in the ability to rate faces as less untrustworthy. "None of these measures changed significantly in the placebo group," Dr. Pedersen said.
The improvements in social functioning are of note, because this is an aspect of schizophrenia that is a major cause of disability, and which tends to respond poorly to antipsychotic medications, according to Dr. Pedersen. The improvement seen with respect to neurocognition might further improve social and general functioning in patients with schizophrenia, he added.
Not all recent studies of oxytocin in schizophrenia have resulted in positive findings. In fact, a third proof-of-concept study by Dr. Kelly and her colleague, Dr. Mary Lee of the National Institute on Drug Abuse, did not demonstrate significant differences between oxytocin and placebo on many of the measures used in the two positive proof-of-concept studies. Thus, it remains unclear whether higher doses and longer duration of treatment would improve outcomes.
"The exciting thing is that these questions will hopefully be answered in several ongoing trials with higher doses," Dr. Feifel said, noting that one trial currently underway is evaluating doses ranging from 40 IU to 160 IU given for longer durations.
Dr. Pederson noted that he "won’t be surprised at all if [treatment with oxytocin] augments nonpharmacologic interventions such as social, cognitive, and neurocognitive training."
"Also, it may be more effective if treatment starts early in the course of disease rather than after a patient has been sick for decades," he said.
Dr. Kelly disclosed a financial relationship with Bristol-Myers Squibb. Dr. Pedersen disclosed holding a U.S. Provisional Patent Application, and receiving research support from the Foundation of Hope for Research and Treatment of Mental Illness and from the Stanley Medical Research Institute.