— New mental health treatments must be approached with caution
Smita Das, MD, PhD, MPH
February 5, 2023
Almost a quarter of U.S. adults suffered from a mental illness in 2021, yet less than half of them received treatment. This has incredible impacts on individuals, families, the economy, and public health, and it is of utmost importance to address these untreated mental health needs. Understandably, innovation is important as people are often looking for creative solutions to treat their mental health concerns. Partially as a result, there has been a proliferation of “edgier” approaches, such as boutique ketamine infusion clinics and at-home psilocybin therapies, which are not yet FDA approved for psychiatric indications or may not be supported by rigorous research.
As headlines and industries tout these approaches (without qualifying the need for use in protocolized ways with medical supervision), the general consumer may seek those treatments to find relief. But to keep patients safe and to effectively treat them, we can’t let industry get ahead of the science, research, and guidelines, whether it be with ketamine or any other similar substance.
With respect to ketamine, clinics are advertising the treatment of many mental health disorders — and it’s becoming increasingly popular. However, the protocols and approaches used by many clinics are not in national practice guidelines, or in some cases not well researched. Ketamine is only FDA approved as esketamine spray (Spravato) for medical use under supervision of a trained prescriber, and only for treatment resistant, severe unipolar major depression without psychotic features. Often, what is being administered in private clinics is not isolated ketamine and is not the nasal spray. In some cases, a psychiatrist or a physician isn’t supervising, and it is not always being given for true treatment-resistant depression. Rather, the medication is being administered off-label. While this is common practice in medicine, it’s generally after more research is available — which we don’t have yet on ketamine. A 2017 consensus statement from the American Psychiatric Association provides an excellent summary and guidance on off-label use of ketamine given the state of the research to that point. At that time, only 147 cases were available.
Ketamine is also not without risks. Even esketamine spray, which has been studied and FDA approved, has boxed warnings with risks that include sedation, dissociation, and abuse or misuse, and is subject to strict controls on dispensing and administration under a risk evaluation and mitigation strategy (REMS) program. Physicians need to be trained in REMS, can only dispense esketamine spray in a healthcare setting, and are required to monitor patients for 2 hours after dispensation.
If individuals attempt to use these substances on their own or in less structured clinics they risk acute adverse effects, for example a “bad trip,” reckless behavior, worsening of psychiatric symptoms, panic, confusion, rapid heart rate, and possible interactions with other medications. There are also longer-term adverse effects of regular hallucinogen use such as persistent psychosis, ketamine associated cystitis or bladder issues, or even developing a hallucinogen use disorder (addiction). Especially with off label use, the FDA has issued an alert about risks of compounded ketamine nasal sprays made by pharmacies (this is not the FDA approved esketamine, but ketamine). The alert cites cases of people experiencing side effects such as delusion, dissociation, visual hallucination, and panic attacks, as well as abuse and misuse.
Some clinics may not screen patients for risk of adverse effects or whether they meet criteria for use (especially since there is little criteria for use). Furthermore, they may be offering these drugs for diagnoses other than depression, and they may not have psychiatric professionals available on staff. Some are using ketamine off label for other indications, such as pain, obsessive compulsive disorder, anxiety, and even substance use disorders. These clinics are often appealing, offering a fast treatment for long-time suffering. People with depression or other diagnoses may sink a lot of money into the treatments (as often these clinics do not take insurance) with false hopes of finding relief.
I am hopeful for the potential of new therapies in mental health. Some hallucinogens are approved for research via the FDA breakthrough therapy designation, such as MDMA (3,4-methylenedioxymethamphetamine) and psilocybin for post-traumatic stress disorder, but the therapeutic indications are narrow and with highly structured protocols and expert healthcare providers.
On the other hand, decades of research offer evidence-based ways of treating common mental health diagnoses, such as depression and anxiety. These include well established psychotherapy approaches such as cognitive behavioral therapy, medications such as antidepressants, and combinations of those approaches. Unfortunately, people are often not aware of these proven treatments or may not have given these treatments a sufficient trial. My concern is that people with mental health or substance use disorders will spend their time, money, and energy trying treatments that are not as well proven, or worse, may be harmful.
While I am hopeful about the potential for new treatments for mental health, I am wary of clinics that offer ketamine or other substances outside of their approved/recommended uses, especially without a psychiatrist involved. We need to follow the science and clinical guidelines properly to realize the benefit of these potential therapeutics safely. We must encourage our patients — as well as friends or family — who are struggling with mental health symptoms to seek help from evidence-based sources, such as their primary care physicians, therapists, psychiatrists, and health plans.
Smita Das, MD, PhD, MPH, is chair of the Council on Addiction Psychiatry at the American Psychiatric Association. She is also a clinical associate professor of psychiatry and behavioral sciences at the Stanford University School of Medicine.