Background: In the last decades the pharmacological treatment of obsessivecompulsive
disorder (OCD) has been significantly promoted by the effectiveness of selective
serotonin (5-HT) reuptake inhibitors (SSRIs) and the subsequent development of the
5-HT hypothesis of OCD. However, since a large majority of patients (between 40% and
60 %) do not respond to SSRIs or strategies based on the modulation of the 5-HT system,
it is now essential to search for other possible therapeutic targets.
Aims: The aim of this paper was to review current literature through a PubMed and Google
Scholar search of novel hypotheses and related compounds for the treatment of OCD,
with a special focus on the glutammate and the immune systems.
Discussion: The literature indicates that glutamate, the main excitatory neurotransmitter,
might play an important role in the pathophysiology of OCD. In addition, a series of
clinical studies also supports the potential efficacy of drugs modulating the glutamate system.
The role of the immune system alterations in OCD in both children and adults needs to be
more deeply elucidated. In children, a subtype of OCD has been widely described resulting
from infections driven by group A streptococcus β-hemolitic and belonging to the so-called
"pediatric autoimmune neuropsychiatric disorders associated with streptococcus" (PANDAS).
In adults, available findings are meager and controversial, although interesting.
Conclusion: The glutamate and the immune systems represent two intriguing topics of research
that hold promise for the development of open novel treatment strategies in OCD.