By Douglas McWilliams M.D., Board Certified Psychiatrist – Columbia, MD
Virtual Appointments Across Maryland, Wisconsin, and Virginia
There is a growing narrative building around intranasal ketamine: it’s a breakthrough for the most severe cases of depression, a lifeline when nothing else works. Those statements are largely accurate. But, what does it mean when “nothing else works”?
As a psychiatrist practicing in Columbia, Maryland and seeing patients virtually across Maryland, Virginia, and Wisconsin, I regularly evaluate people who have tried ketamine with little to no legimitate treatment history. Brand new patients often ask about starting with ketamine immediately without having tried anything else. This article is an attempt to offer a more complete picture – one that takes ketamine seriously – while being realistic about when it’s the right tool, and when it isn’t.
Insurance: A Low Bar with High Consequences:
Most insurance plans that cover esketamine (Spravato), the FDA-approved intranasal form of ketamine, require documentation of two failed antidepressant trials. At first, this sounds reasonable. Why continue with a series of medications when things aren’t working? In reality, it barely scratches the surface of available and unique treatment options.
The antidepressant landscape is vast. SSRIs, SNRIs, TCAs, MAOIs, tricyclic antidepressants, atypical antidepressants… Add augmentation strategies like lithium, thyroid supplementation, and atypical antipsychotics and you have dozens of clinical options. Two failed trials may mean a patient tried any of these combinations – whether or not they were appropriate. The reason for discontinuation doesn’t even have to be lack of benefit. Side effects are the single most common reason for medication discontinuation early in treatment, even if they are expected to resolve or improve. Patients don’t even have to demonstrate they were on a therapeutic dosage. Two failed trials is not treatment resistance.
Beyond medication, many patients who meet the two-failure threshold have never completed an adequate course of evidence-based psychotherapy, which has robust efficacy data – especially when combined with a medication. Often, the patient may not have addressed contributing factors like untreated sleep disorders, hypothyroidism, chronic pain, or alcohol use that sustain depression. The insurance threshold doesn’t capture this nuance.
Just because insurance covers it doesn’t mean it is the right choice. Having a psychiatrist well-versed in these matters can make a real difference.
Ketamine is Not a Low-Risk Intervention:
Proponents of ketamine tend to downplay the risks.
Addiction potential is real. Ketamine is a Schedule III controlled substance with well-documented historical abuse liability. It produces dissociative euphoria that can be psychologically reinforcing, and repeated use at sub-anesthetic doses (like treatment of depression) has been associated with dependence in recreational users for decades. While ketamine has fallen out of the mainstream recreational drug use environment. The clinical population receiving ketamine for depression is not protected from the same societal and neurobiological process that became a problem in the 90s. Patients with personal or family histories of substance use disorders warrant particular caution that is not always applied in ketamine clinic settings. That being said, the vast majority of data demonstrates a low addiction potential if used as part of an acute treatment course for depression.
Ketamine bladder syndrome and other physical harms. Chronic ketamine use is associated with a painful and sometimes irreversible condition known as ketamine-induced uropathy, or ketamine bladder syndrome. This is characterized by severe urinary tract inflammation, reduced bladder capacity, and in serious cases, the need for surgical intervention. While rare, the threshold for harm in a clinical maintenance population remains poorly understood.
Cognitive and dissociative effects. Ketamine produces a period of dissociation, perceptual distortion, and cognitive impairment. The long-term cognitive effects of repeated sub-anesthetic ketamine exposure in humans are not fully established. Ketamine is newly approved for use in treatment-resistant depression, and clinicians need to be more upfront about the uncertainty.
That being said, none of these risks make ketamine wrong for depression. However, these issues warrant serious, informed consideration. Ketamine should not be a default escalation in treatment only because it becomes available.
The Exit Strategy Problem:
Perhaps the most underappreciated risk of ketamine for depression is not what happens during treatment, but what happens when treatment ends.
Ketamine’s antidepressant effect is rapid but short-lived. The typical response window is days to a couple of weeks. Unlike a conventional antidepressant, which a patient takes daily and can be tapered gradually when the time is right, ketamine requires ongoing administration to work. This is tricky with ketamine, and many patients transition to an indefinite maintenance schedule without a clearly defined endpoint. At some point, insurance stops paying – yet the patient is stuck on the maintenance schedule.
The maintenance period is essentially a clinical dependency – on a controlled dissociative anesthetic – with no established ceiling and no established exit strategy. When patients do eventually stop, relapse rates are high. The field hasn’t quite figured this out yet. Research on ketamine discontinuation is still developing, but clinical experience consistently shows that the underlying depression has often not been addressed in any meaningful way.
Contrast this with a well-executed course of psychotherapy combined with pharmacotherapy, where the explicit goal is skill-building and the development of internal resources that persist after treatment ends. Ketamine, as typically deployed, offers no such architecture. For patients considering ketamine make sure to discuss this issue with your provider, so you approach treatment from an informed position.
Who Should Actually Be Receiving Ketamine
This article may come across as entirely negative. To be clear: this is not an argument against ketamine. Ketamine is a potential breakthrough intervention. I have seen first-hand peoples lives change dramatically in a positive fashion after completing a treatment course of ketamine. I maintain professional relationships with ketamine providers both locally in the Maryland area and nationally, and I refer patients for ketamine treatment on a regular basis.
Ketamine is a great option for true treatment-resistant depression. That means multiple adequate medication trials across different medication classes, evidence-based psychotherapy, optimization of contributing medical factors, and trials of augmentation strategies.
The issue is that the system, as currently structured, is moving patients toward that intervention before they belong there. A two-antidepressant threshold incentivizes escalation over optimization. It funnels patients into a cash-cow treatment pathway that is expensive to patients, but lucrative for the clinic and administering provider.
Working With a Psychiatrist Before and Alongside Ketamine
If you’re in Maryland, Virginia, or Wisconsin and you’ve been told ketamine might be the right next step, it’s worth having a thorough psychiatric evaluation first — one that looks at the full picture of your treatment history, your diagnosis, and what hasn’t yet been tried or optimized.
My practice offers virtual psychiatric care across Maryland, Virginia, and Wisconsin, with a focus on comprehensive medication management and thoughtful, evidence-based treatment planning. For patients who do ultimately pursue ketamine, I’m also able to provide coordinated psychiatric care alongside ketamine treatment.
The most responsible path forward is to reserve it for those who have genuinely run out of alternatives, not for those who have simply run out of patience with a system that hasn’t yet offered them the right options.
References:
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Daly, E. J., Trivedi, M. H., Janik, A., et al. (2019). Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: A randomized clinical trial. JAMA Psychiatry, 76(9), 893–903. Link
Gaynes, B. N., Asher, G., Gartlehner, G., et al. (2018). Definition of treatment-resistant depression in the Medicare population. Agency for Healthcare Research and Quality. Link
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Douglas McWilliams, M.D. is a board-certified psychiatrist based in Columbia, Maryland, offering virtual psychiatric services to patients throughout Maryland, Virginia, and Wisconsin. He does not provide ketamine treatment but collaborates with ketamine providers locally and nationally as part of comprehensive, individualized care.
This article is intended for educational purposes and does not constitute medical advice. If you are experiencing a psychiatric emergency, please contact 988 (Suicide & Crisis Lifeline) or go to your nearest emergency room.