Working to better understand OCD
Some of our research studies apply established treatments or involve testing new ones. Other studies are investigating brain changes that may contribute to OCD, using genetic tests, brain scans, and other approaches.
We have studies for people with OCD and for people with OCD-like symptoms but who would not qualify for a diagnosis. We also have research studies for people that do not have any significant OCD symptoms.
Participants are compensated for their time upon completion of research studies.
What to Expect
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The first step in participation is a phone call to our clinic. During this call, a member of our clinic staff collects some basic information about people's symptoms and history and answers questions they may have about the Clinic and its operations.
If it seems like a person might be a good match for our research program, they are invited to make an appointment for an initial screening visit. At this screening, clinic personnel collect more detailed information about their symptoms and history. We seek to understand not only their OCD symptoms, but also other psychiatric or medical symptoms they may have, how the symptoms have affected their life, and what treatments they have tried in the past. This screening may also involve laboratory tests to make sure that people have no medical conditions that might preclude participation in research.
Clinic psychiatrists and psychologists are happy to communicate any treatment recommendations they may have to a person's own treatment provider. If they do not have an established treatment provider, we can often give some referrals.
Depending upon which study or studies people will be participating in, after the initial screening visit, they are asked to come back for one or more follow-up appointments to complete specific research protocols. For most of our studies, we are able to pay research participants a small amount of money as a ‘thank-you’ for participation.
Treatment Studies
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Brain Network Changes Accompanying and Predicting Responses to Pharmacotherapy
HIC: 2000023688
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 (ClinicalTrials.gov identifier: NCT04131829)
Troriluzole augmentation for the treatment of refractory OCD
Closed to recruitment.
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
Closed to recruitment.
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 (ClinicalTrials.gov 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).
Non-Treatment Studies
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Modulation of Functional Connectivity and Fear Extinction Abnormalities
HIC 2000039024
The purpose of this study is to test whether transcranial direct current stimulation (tDCS), a form of safe and mild electrical stimulation, affects processes in the brain related to the treatment of anxiety. Three MRI brain imaging scans will also be completed during this three-day study.
Brain imaging in tic disorders and OCD
HIC: 2000021811
Evidence indicates that dopamine may be dysregulated in people with tic disorders and potentially in those with OCD as well. We are using positron emission tomography (PET), a form of non-invasive brain imaging, to examine dopamine receptor activity among people with and without both tics and OCD. We hope to better understand if and how dopamine dysregulation may be involved in tic disorders and OCD.
Individually Measured Phenotypes to Advance Computational Translation in Mental Health (IMPACT-MH)
HIC: 2000036987
This study is investigating how mental health symptoms change and develop over time, among people with OCD as well as other mental health conditions. We will be collecting clinical information using various methods, including interviews, questionnaires, and computer tasks. These appointments will be both in-person and virtual over the course of about two years.
Exploring the genetics of OCD
HIC 0803003626
It is clear that the risk for developing OCD depends in part on our genes; but the specific genes that contribute to OCD, and how they do so, are not well understood. Patients who we see in our clinic have the opportunity to give blood for genetic analysis. By comparing the specific genes of patients with OCD with other patients or with individuals with no psychiatric diagnosis, we hope to better understand the various complicated factors that contribute to the genetics of the illness.
Exercise and OCD
HIC: 2000040629
Research suggests exercise can bring psychological benefits to people with OCD. It has also been shown to improve performance on tasks of cognitive flexibility, which is often impaired in OCD. This study is testing how a single session of low or moderate intensity exercise may affect both cognitive flexibility and symptom reactivity in people with OCD.
ClinicalTrials.gov ID: NCT07103902