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 (ClinicalTrials.gov identifier: NCT04131829)
Trigriluzole 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, trigriluzole, in people with OCD. Trigriluzole 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.
This is a registered clinical trial (ClinicalTrials.gov identifier: NCT03299166).
Real-time fMRI neurofeedback research trial
Real-time functional magnetic resonance imaging (fMRI) neurofeedback is a new technique that allows us to train people to control their brain activity patterns. In this research we are investigating whether real-time fMRI neurofeedback can help people control activity in the region of the brain that has been implicated in obsessive-compulsive symptoms-, and whether the neurofeedback reduces these symptoms.
Participation in this study involves multiple visits to the Magnetic Resonance Research Center at the Yale School of Medicine. People will participate in four imaging sessions in which they are asked to try to control their brain patterns. The imaging sessions are non-invasive but do involve exposure to symptom provoking images. The full study takes approximately a month to complete.
This is a registered clinical trial (ClinicalTrials.gov identifier: NCT02206945) and is funded by the National Institute of Mental Health (R01 MH100068).