Specialized Clinic Broadens Scope to Manage Patients with Treatment-Resistant Psychiatric Illness

Consultation service provides comprehensive care to patients with anxiety, PTSD, schizophrenia, and other high-risk disorders

Illustration of brain maze

An innovative new program may provide hope to patients with psychiatric disorders that have failed to respond to mainstream therapies. Cleveland Clinic’s Psychiatric Treatment-Resistance Program (formerly called the Treatment-Resistant Depression Clinic) has now been expanded to provide comprehensive evaluations and care to patients with a wider variety of serious, refractory mental health conditions.


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“Conventional treatments — including medications and cognitive behavioral therapy — while effective for some, are not effective for all,” explains Brian Barnett, MD, a psychiatrist in the Center for Adult Behavioral Health at Cleveland Clinic Lutheran Hospital and co-director of the hospital’s Treatment-Resistant Depression Clinic. “Our goal is to provide an easy-access, centralized service where patients struggling with difficult-to-treat psychiatric conditions can benefit from the most advanced therapies modern medicine has to offer. This program was born out of an urgent need to find better treatments for those who are suffering.”

Launched in February 2024, the new program is designed to address a range of treatment-resistant conditions, including bipolar disorder, catatonia, generalized anxiety disorder, major depressive disorder, obsessive-compulsive disorder, post-traumatic stress disorder and schizophrenia/schizoaffective disorder.

Groundbreaking therapies

In general, treatment resistance is defined as a failure to achieve remission from symptoms after cognitive behavioral therapy and two or more medication trials. A large minority of patients with psychiatric illness (30%-40%) have a treatment-resistant version of their disorder, says Barnett.

“Our faculty has significant expertise in a wide variety of psychiatric conditions and treatment modalities, so we’re uniquely prepared to provide a path forward for patients dealing with hard-to-treat disorders,” he says. “In addition, we recognize the importance of ongoing therapeutic alliances and are eager to support other providers in their desire to find solutions to their patients’ most persistent symptoms.”

Cleveland Clinic’s consultation-based program provides an array of advanced primary therapies, including electroconvulsive therapy, transcranial magnetic stimulation, and intranasal esketamine (Spravato). In certain cases, vagus nerve stimulation or deep brain stimulation may be provided. Patients with PTSD may also be offered a stellate ganglion block, which has been shown to mitigate overactivity in the sympathetic nervous system.

The program is based on a collaborative treatment model that enables patients to retain relationships with their existing outpatient prescribers, explains Barnett. All available treatment options are discussed during the patient’s initial consultation – an approach that helps reduce gaps in treatment and provides patients with a more comprehensive understanding of the potential benefits and risks of available therapies. In addition, the clinic makes advanced pharmacological recommendations to referring providers. In some cases, patients may be advised to pursue a higher level of care through one of Cleveland Clinic’s intensive outpatient programs.


“We’re fortunate to have a wide range of inpatient and outpatient programs capable of delivering compassionate, personalized care to those with complex psychological, emotional and social difficulties,” says Barnett.

Looking ahead

In addition, Cleveland Clinic investigators are currently conducting clinical trials on the therapeutic potential of classic hallucinogens like psilocybin, lysergic acid (LSD) and mescaline for the treatment of mental illness. Barnett emphasizes that a growing body of research points to the transformative role these substances may soon play in Western Medicine.

This forward-thinking approach has sparked the interest of referring physicians both within and outside Cleveland Clinic. The number of provider referrals received by Barnett’s team has doubled since the new program began. Although most of these referrals come from behavioral health providers, the program is poised to expand its reach by strengthening its relationships with primary care providers.

“It’s easy for clinicians to feel stuck when managing patients with treatment-resistant psychiatric conditions; they don’t know where to turn,” he explains. “We’re excited about the opportunity to educate providers about interventions that may be unfamiliar – or unavailable – to them. Our goal is to provide a place where clinicians can work together to elevate our understanding of treatment-resistant mental illness.”

For additional information, please email psychtreatresistprog@ccf.org or call (216) 363-5730, option 3.


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