Traci L. Turner, PharmD
PGY2 Psychiatric Pharmacy Resident
Speaker Heidi Wehring, PharmD, BCPP, provided information at CPNP 2014 in an effort to answer the question of Negative Symptoms in Schizophrenia: A Place for Oxytocin? Negative symptoms of schizophrenia are often the most functionally debilitating symptoms. They are present in two clusters: (1) deficits in emotion expression such as alogia and blunted affect, and (2) avolition, which can also been seen with asociality and anhedonia. Patients with severe negative symptoms often have a decreased response to interventions. They may also have a reduction in emotional responsivity, speech, movement, and motivation.
Studies have shown an inverse relationship between negative symptoms and functional outcomes. A study by Strauss et al. explored the differences between two groups of patients based on the two clusters above (deficits in emotion expression versus avolition). They concluded that patients with high scores for negative symptoms, no matter which cluster they were in, had worse scores in attitude, work, family role function, and independent living.
Currently, there are no FDA approved medications for the treatment of negative symptoms. Clozapine was originally thought to have superior efficacy when compared to other antipsychotics for the treatment of negative symptoms, but meta analyses and clinical trials have shown that this may not be true for patients with primarily negative symptoms. While adjunctive treatments and non-pharmacologic interventions are being explored, oxytocin is beginning to establish its role for treating negative symptoms.
Oxytocin, the “love hormone”, is currently used for induction/augmentation of labor, prevention/treatment of postpartum hemorrhage, stimulation of milk ejection, and prevention of mastitis. At first glance, it doesn’t appear to have much relation to the treatment of negative symptoms. However, it has been linked to having an effect on both social behaviors (such as social memory and sexual arousal) and non-social behaviors (i.e., learning, memory, and stress). Oxytocin has begun being explored for negative symptoms because of its interaction with serotonin, dopamine, and glutamate systems.
Early studies found that central levels of oxytocin often showed a disruption in oxytocin systems in patients with schizophrenia. Interestingly, these studies showed differing results on this abnormality, with some patients having increased levels, and others having decreased levels. Patients with higher oxytocin levels were noted to have more prosocial behavior. Low levels of plasma cortisol have also been noted in patients with greater negative symptoms severity.
Four recent studies have reported findings on the impact of oxytocin on negative symptoms. It should be noted though that these studies did not use negative symptoms as the primary outcome measure. The findings, however, can be used as a springboard for future studies.
Many questions still remain regarding the use of oxytocin. The optimal dose, frequency, route, and duration of administration still needs to be established. Additionally, whether or not oxytocin is more effective in different treatment settings could be explored. Finally, researchers can focus on the two different symptoms clusters described above and decide if these have an impact on therapy.