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Ketamine for mental health conditions: What every primary care physician needs to know

Wait times to find high-quality mental health support continue to be an issue, lagging from weeks to months in, leading to primary care physicians (PCPs) assuming a large role in addressing the pressing shortage of mental health services. Acting as the point of entry into the mental health care system, PCPs are encountering patients with complex mental health challenges who are often unable to secure appointments with specialists for several months, both asking for support and for counsel on some of the newer, more novel therapies that are gaining traction within the mental health field, such as ketamine.

Ketamine is becoming increasingly known for its potential to help patients with treatment-resistant depression and suicidal ideation who have not been helped with traditional oral antidepressants. Although ketamine has been used in medicine for decades as a general anesthetic and is on the World Health Organization’s list of essential medicines, its potential in mental health is only now gaining momentum for a growing number of clinically effective applications.

Despite this momentum, misconceptions and myths cloud the truth about ketamine use. This is particularly both a problem and an opportunity as PCPs who carry a heavy caseload of patients needing mental health care need the right information to appropriately support their patients.

PCPs should be aware of these five crucial factors regarding ketamine administration and use when discussing treatment choices with patients:

Determining who is and who is not a good candidate for ketamine. Ketamine therapy has shown success in treating depression, anxiety, bipolar depression, and suicidal ideation. It’s a game-changer for treatment-resistant depression. However, not everyone is a suitable candidate, including patients with specific conditions like uncontrolled hypertension, liver issues, allergies, substance use disorder, or taking certain medications. These are high-level considerations that PCPs can use to more easily navigate conversations with patients, ruling out ketamine from the start for patients where the risks may outweigh the benefits.

Ensure safe administration of ketamine. Any individual who’s receiving ketamine for mental health support should have a comprehensive mental health and safety assessment by a trained mental health clinician prior to initiating treatment. Ketamine is not the treatment plan; it is part of a treatment plan — working collaboratively with a trained mental health clinician is key. Any licensed clinician with a DEA number can prescribe ketamine; however, any non-psychiatrist prescribing ketamine to a patient for psychiatric indications should ensure that the patient is under the care of a mental health professional. Ketamine may be administered by an anesthesiologist, a CRNA, or a psychiatric clinician, but it is important that they work collaboratively with a mental health professional on the team.

Different ways to administer ketamine to patients. There are several ways to administer ketamine, but the most research is with IV-administered ketamine, which is also known as ketamine infusion therapy. A recent peer-reviewed study showed significant benefits for patients with depression, anxiety, and suicidal ideation who received ketamine infusion therapy. There is also an FDA-approved version of ketamine, Spravato® (esketamine), that is intranasal and shown to be effective for patients with severe depression and for those who, despite trying at least two antidepressant treatments, have not responded. Spravato is the only form of ketamine that has widespread insurance coverage for a mental health indication.

Importantly, research shows us that pairing ketamine, given in any mode, with psychotherapy (also known as ketamine-assisted therapy) may help prolong its benefits.

Ketamine and substance misuse. David Nutt, a respected psychiatrist, neuroscientist, and the Director of the Neuropsychopharmacology Unit in the Division of Brain Sciences at the Imperial College London, has researched how ketamine is not more addictive than benzodiazepines or stimulants. As with any potentially addictive drug, any clinician prescribing ketamine needs to monitor for signs of tolerance (for example, needing higher doses to get the same effect) and dependence (i.e., needing more frequent dosing to avoid withdrawal symptoms). Some sequelae of chronic ketamine abuse include cognitive problems and a potentially irreversible hemorrhagic cystitis.

Variations in duration of treatment. A typical course of treatment, studied in research, is six IV ketamine treatments in two weeks; however, this varies from patient to patient. This fact is frequently misunderstood, and it’s important that both patients and clinicians understand that there is a spectrum. Some patients may require treatments every five years, while others weekly. The best way to determine this is to work closely with a clinician with extensive experience with ketamine for mental health conditions. Relief from symptoms after a ketamine treatment is rapid, but maintenance is key to sustaining those effects. What that looks like for a given patient varies based on their specific conditions.

The trend of PCPs being approached for mental health support is already the new normal and has been for some time. The resurgence of therapies like ketamine, psychedelics, and other approaches such as transcranial magnetic stimulation (TMS) signifies a new era in mental health care and addresses an unmet need to bring more treatment options to address mental illness. There has been a lot of progress in mental health, and psychiatry already looks vastly different than it did even a few years ago. However, misinformation and stigma persist. To ensure the success of these treatments, PCPs play an important role in building trust and meaningful connections to both debunk myths and bring data-driven mental health care to the people who need it most.

Carlene MacMillan is chief medical officer, Osmind, a public benefit corporation dedicated to aiding clinicians and researchers in advancing life-saving mental health treatments. In this role, she concentrates on product development, growth initiatives, and medical affairs. Dr. MacMillan is also a co-founder of Fermata Health, an interventional psychiatry practice located in Brooklyn, NYC. She can be reached on X @CarleneMac.

L. Alison McInnes is a psychiatrist and vice president of scientific affairs, Osmind, with over 30 years of clinical experience, including teaching and research in academic and HMO settings. Dr. McInnes was an associate professor at Mount Sinai from 2001 to 2008, heading an NIMH-funded lab investigating the genetic basis of psychiatric disorders. She then founded and ran the regional ketamine therapy program at Kaiser Permanente in Northern California. In addition to her full-time role at Osmind, she provides limited patient care for individuals with complex medication management needs, including ketamine-assisted psychotherapy.


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