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Treatment Studies

Brain Network Changes Accompanying and Predicting Responses to Pharmacotherapy

Current treatments for OCD benefit about 60-70% of people, but many do not experience adequate relief. There is a need to identify predictors of treatment response. In this study, we will use state-of- the-art neuroimaging to identify predictors and correlates of response to a standard medication-based treatment for OCD. In clinical practice, this may aid proper treatment selection and improve outcomes. Identifying predictors of treatment response will also shed light on the mechanisms of therapeutic change, and highlight potential targets for anatomically-based treatments, such as transcranial magnetic stimulation and neurofeedback.

This 18-week study is designed to examine whether brain scans can predict how well individuals will respond to standard medication treatment, and what changes in the brain over the course of treatment correspond to improvement in symptoms. Participants will receive fluoxetine (also known as Prozac), and take part in a series of brain imaging and symptom assessments. Fluoxetine is a standard treatment for OCD, and has been approved by the U.S. FDA for treatment of OCD in both adults and children. Some participants will receive fluoxetine from the beginning of the study. Others will initially receive a placebo pill (which contains no active drug) for a period of time before beginning fluoxetine. Every participant will receive a proper trial of fluoxetine over the course of this study. At the end of the study, participants can choose whether they wish to continue taking fluoxetine after consultation with study physicians and their own doctor.

This is a registered clinical trial ( identifier: NCT04131829)

Troriluzole augmentation for the treatment of refractory OCD

Several lines of evidence suggest that the neurotransmitter glutamate is overactive in at least some cases of OCD. Medications that modulate glutamate in the brain may therefore represent a new avenue to treat OCD symptoms, and may be of use in patients whose symptoms do not respond well to standard methods of treatment. Some years ago, the Yale OCD Research Clinic began investigating the glutamate-modulating drug riluzole (Rilutek®), which is FDA-approved for the treatment of the neurological disease amyotrophic lateral sclerosis. In early research, without a control group, we found riluzole to be helpful to some people with severe, treatment-refractory OCD, and that this benefit can persist for over a year after initial treatment. In a follow-up placebo-controlled study, funded by the National Institute of Mental Health, and published in 2015, we again found evidence for benefit in some people, though the study was not large enough to constitute definitive proof.

Our current research, performed together with the pharmaceutical company Biohaven, and with collaborating sites across the country, aims to test the efficacy of a similar new medicine, troriluzole, in people with OCD. Troriluzole has been designed to be more convenient and easier to use than riluzole, with fewer side effects. Once in the body, it is transformed into riluzole, and thus we expect it to have similar benefits. Through this placebo-controlled study, we hope to better understand whether or not glutamate-modulating medications have a role in the treatment of OCD after first-line medication has been tried, and to take an important step towards making a new glutamate-targeting treatment available to people.

Neural correlates of the effects of psilocybin in OCD

Previous research has suggested that psilocybin may reduce OCD symptoms, but this has never been tested in a controlled study. We are investigating whether a single dose of psilocybin can lead to improvement in OCD symptoms and/or brain changes in comparison with a placebo control. Participants will receive either psilocybin or placebo. Several preparatory sessions prior to drug administration will ensure comfort and safety. These sessions will also provide a psychological framework to guide participants’ experience. The drug will be administered in a comfortable setting with two clinical facilitators. Psychological and medical monitoring will be provided. If given placebo, participants will be invited to receive psilocybin at a later date. After receiving psilocybin, there will be multiple follow-up evaluations over a span of 12 weeks.

This is a registered clinical trial ( identifier: NCT03356483).

Effects of Repeated Psilocybin Dosing in OCD

Study HIC#:2000032623


This study aims to investigate the potential effects of repeated dosing of oral psilocybin on OCD symptoms. It will also assess psychological mechanisms that may underlie any therapeutic effects. Participants will be randomized to receive either immediate treatment (two doses oral psilocybin separated by one week) or delayed treatment (7 weeks post-randomization).

The first dose will be standardized at 25 mg of psilocybin, and the second dose will be either 25 mg or 30 mg. The second dose will be determined after the first dose and based on whether there is a clinically significant response from baseline. Follow-up assessments are up to 12 months post-second dosing week.

This study is conducted entirely on an outpatient basis with the possibility of remote/virtual follow-up visits after each dosing session. The dosing sessions last the entire day, and participants must be medically cleared prior to returning home with assistance (e.g., driven by a family member or friend, or ride share).