Message from the Chair: Developing New Treatments for Mood and Anxiety Disorders

In the last decade, significant advancements have been made in basic neuroscience. Despite such efforts, finding a way to translate these discoveries into new therapeutics for Mood and Anxiety Disorders remains a challenge. Unfortunately, most of the medications that are currently available are a result of serendipitous observation, rather than bench-to-bedside research. In many cases, these treatments have limited efficacy. Even when effective, a patient typically waits several months to experience relief.

Multiple factors have stymied the progress of novel therapeutics, including pinpointing the disease-relevant brain targets, diagnostic heterogeneity, absence of reliable biomarkers, and overreliance on subjective clinical measures to assess outcomes. Given the high failure rate of new treatments during development and the exorbitant cost of bringing a drug successfully to market—which is estimated to be over $1.2 billion—it is not surprising that the pharmaceutical industry is becoming increasingly risk averse in the psychiatric space.

We are experiencing a crisis in drug and device discovery. One way to address this pressing problem is through innovatively designed proof-of-concept (POC) trials. Recently, the Department of Psychiatry at Mount Sinai was part of a team that received funding from the National Institutes of Mental Health (NIMH) for two separate requests for applications (RFAs) to conduct clinical trials studying new interventions in patients with Mood and Anxiety Disorders. The goal of both studies, which are being coordinated by Massachusetts General Hospital and Duke University Medical Center, is to develop new treatments as quickly and efficiently as possible. Both of these NIMH contracts incorporate experimental medicine design elements, which increase the chances of successfully identifying a new target. During the clinical trial, researchers can make timely decisions regarding whether or not to proceed with further testing of interventions acting on a particular target.

The first study, Rapidly-Acting Treatments for Treatment-Resistant Depression, (RAPID), conducted at Mount Sinai by Dan Iosifescu, MD, Associate Professor of Psychiatry and Neuroscience and Chief of the Mood and Anxiety Disorders Program, aims to develop new quick-acting interventions for Treatment-Resistant Depression. The research will address the important clinical problem of delays in treatment efficacy with current antidepressants.

The second study, Fast-Fail Proof-of-Concept Studies for Mood and Anxiety Spectrum Disorders (FAST-MAS), in which I serve as Mount Sinai’s site Principal Investigator, is intended to identify new molecular targets for Mood and Anxiety disorders and test the clinical efficacy of drugs interacting with such targets. In FAST-MAS, novel and repurposed pharmacological compounds will be rapidly tested in the clinical setting and analyzed for mechanistic brain effects that reflect engagement of the putative brain targets. This can include evidence that the compound engages its molecular target (e.g., via PET receptor occupancy data), or affects clinically relevant neurocircuits as shown by fMRI. In a departure from conventional Mood and Anxiety Disorder trials, FAST-MAS will examine changes in dimensions of psychopathology such as, cognition, positive valence, and reward rather than traditional DSM-based categories.

These studies represent powerful answers to the challenges of treatment development in Mood and Anxiety disorders. Through the use of novel study designs and the investigation of brain mechanisms to test the efficacy of promising interventions, our researchers will be able to expeditiously test these new therapies that may lead to expanded options for patients.

Wayne K. Goodman, MD
Chair of the Department of Psychiatry
Esther and Joseph Klingenstein Professor of Psychiatry
The Mount Sinai Medical Center