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Intranasal Oxytocin May Ease Schizophrenia Symptoms


 

EXPERT ANALYSIS FROM A MEETING OF THE NEW CLINICAL DRUG EVALUATION UNIT SPONSORED BY THE NATIONAL INSTITUTE OF MENTAL HEALTH

PHOENIX – Interest in the use of intranasal oxytocin for the treatment of psychiatric disorders has expanded in recent years, and several new studies suggest that it may have benefit in patients with schizophrenia.

The neuropeptide, which is associated with a wide variety of social behaviors in diverse species, may be particularly suited for treating schizophrenia, Deanna Kelly, Pharm.D., said during a symposium at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

"Schizophrenia is a disorder that is associated with a spectrum of social and emotional deficits, such as impaired perception of emotions, impaired social cue perception, and biased reasoning about certain types of social information. It is also a thought disorder associated with anxiety and mistrust," said Dr. Kelly of the University of Maryland, Baltimore.

It is well established that oxytocin regulates many of these factors, and compelling evidence suggests the oxytocin system is dysregulated in patients with schizophrenia.

Emerging clinical data demonstrate that oxytocin administrated via the intranasal route, which is believed to provide a favorable pathway for the peptide into the central nervous system, provides benefit with respect to emotion recognition, positive and negative core symptoms, social cognitive measures, and neurocognition.

In one double-blind, placebo-controlled, crossover study, oxytocin was shown to improve emotion recognition, Bruno Averbeck, Ph.D., reported. In an initial experiment, 30 stable, medicated community-dwelling patients with schizophrenia and 29 control subjects matched for age and IQ completed an emotion discrimination task involving images of facial expressions representing specific emotions. Some images included a single emotion, and others were morphed images, depicting two commonly confused emotions such as surprise and fear.

Patients with schizophrenia were less able than controls to accurately recognize emotions using both unmorphed and morphed images, although both groups performed worse on identifying morphed emotions, said Dr. Averbeck of the National Institute of Mental Health.

In the crossover study, the effects of one 24-IU dose of oxytocin on the same emotion recognition task were measured in 21 patients with schizophrenia. Compared with performance without oxytocin, there was a 25% improvement in emotion recognition following oxytocin treatment, with improved recognition of certain emotions, such as happiness and sadness, but not others, such as surprise, he said (Psychol. Med. 2012;42:259-66).

A possible explanation for the improved performance on emotion recognition tasks following intranasal oxytocin administration is increased saccades to the eye region. A great deal of emotion is expressed through the eyes, and patients with schizophrenia are prone to avoidance of the eye region, Dr. Averbeck explained, noting that prior studies in patients with autism have shown that oxytocin increases saccades and emotion recognition.

In two other proof-of-concept trials, intranasal oxytocin was found to significantly reduce both positive and negative schizophrenia symptoms, and to improve social dysfunction.

A team of researchers at the University of California, San Diego (UCSD), conducted one of the studies – a randomized, placebo-controlled crossover trial of 15 adult patients with residual symptoms despite therapy. In the trial, either placebo or intranasal oxytocin, taken daily for 3 weeks and titrated to 40 IU (5 sprays) twice daily, was given in addition to stable doses of antipsychotic medication. The order of placebo and oxytocin was randomly assigned with a 1-week washout between treatments (Biol. Psychiatry 2010;68:678-80).

Oxytocin treatment for 3 weeks significantly reduced scores on the Positive and Negative Symptoms Scale (PANSS), with a difference of 5.46 points between groups on total scores. Clinical Global Impression-Improvement Scale (CGI-I) scores also were significantly improved in the treatment group, compared with placebo after 3 weeks of treatment, said Dr. David Feifel of UCSD, who led the study.

The findings support those of prior studies that also have demonstrated antipsychotic effects of oxytocin, and which have suggested oxytocin’s ability to ameliorate the symptoms of schizophrenia, he said.

In a separate proof-of-concept study, a team of researchers at the University of North Carolina, Chapel Hill (UNC), also found that after controlling for baseline measures, oxytocin treatment was associated with significantly greater declines in PANSS total scores, compared with placebo (least squares mean differences of 70.56 vs. 77.21), and with trends toward significantly greater declines vs. placebo in PANSS general subscale scores (least squares mean differences of 34.34 vs. 38.26).

In that 14-day parallel-arm study, led by Dr. Cort A. Pedersen of UNC, 14 adult patients were treated with 24 IU of intranasal oxytocin twice daily in addition to their stable regimens of antipsychotic medication, and 11 received placebo.

In both of these proof-of-concept studies, intranasal oxytocin was well tolerated, and also produced improvement on highly relevant secondary measures.

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