In the rising global mental health epidemic severe challenges, such as depression, anxiety, and post-traumatic stress disorder (PTSD), continue to significantly impact employee well-being and productivity. Employers are increasingly seeking effective and innovative solutions to support workforce mental health. An intriguing treatment option that has emerged in recent years is ketamine assisted therapy. Although previously known primarily as an anesthetic, a robust and growing body of scientific evidence suggests that ketamine can produce rapid and powerful therapeutic effects for people struggling with difficult-to-treat mental health conditions.[1,2]

By considering ketamine therapy as an employee health benefit, organizations have an opportunity to provide access to potentially transformative treatment, for those who have not found adequate relief through standard treatment approaches. This inquiry provides an examination of some key research supporting ketamine’s therapeutic potential, highlights the potential benefits of ketamine therapy, and offers guidance for employers considering adding this valuable treatment option.

Clinical Evidence: The Robust Science Supporting Ketamine Therapy

Numerous well-designed studies have consistently demonstrated the remarkable efficacy of ketamine in treatment-resistant mental health conditions, particularly in depression. Randomized controlled trials have repeatedly shown that ketamine infusions can dramatically reduce depressive symptoms, often within a matter of hours – an exceedingly rare and valuable characteristic for a psychiatric treatment.[1] A comprehensive 2019 meta-analysis of 11 gold-standard trials concluded that a single ketamine infusion produced antidepressant effects far superior to placebo.[3] This strong evidence establishes ketamine as an important treatment for those who have not been assisted by currently available therapies.

The benefits of ketamine extend beyond intravenous administration. Esketamine, an FDA-approved nasal spray formulation, has also demonstrated rapid and clinically meaningful antidepressant effects in rigorous trials.[4] When added to oral antidepressants, esketamine nasal spray produced significantly greater symptom improvement than placebo. While additional long-term data will be invaluable, the evidence to date supports both IV and intranasal ketamine as powerful new options in the antidepressant armamentarium.

The therapeutic potential of ketamine is not limited to depression. A growing body of research indicates that it may also provide much-needed relief for anxiety disorders, PTSD, OCD, substance use disorders, suicidal ideation and certain pain conditions.[2,5,6,14] For example, a randomized trial found that IV ketamine dramatically outperformed a psychoactive placebo in rapidly reducing PTSD symptoms.[5] The ability to meaningfully alleviate symptoms across numerous serious conditions further magnifies ketamine’s potential to improve employees’ mental health on a broad scale.

Researchers believe ketamine’s wide-reaching effects may stem from its ability to promote neuroplasticity, the brain’s capacity to adapt and form new connections, as well as its modulation of key mood-regulating neurotransmitters like glutamate.[7,15] By helping the brain “rewire” maladaptive patterns underlying mental illness and restoring healthy neurotransmission, ketamine may offer a uniquely rapid and direct neurophysiological reset.

While extremely encouraging, the studies conducted to date have some limitations. Additional larger-scale, longer-term trials will help to further refine ketamine treatment protocols, establish the durability of benefits, and inform long-term safety and monitoring of best practices. Like any treatment, ketamine is not without risks, including the potential for abuse, and will require careful patient selection and ongoing supervision.[1,2] However, in light of the profound unmet needs in mental health treatment and the often-devastating consequences of severe and persistent mental illness, impressive evidence for ketamine’s strong efficacy and good overall safety profile establishes a highly favorable risk-benefit profile that deserves serious consideration.

Potential Benefits and Considerations for Offering Ketamine Therapy Coverage

For employers evaluating how best to support and invest in workforce mental well-being, the inclusion of ketamine therapy in health benefit packages may yield substantial advantages. First, covering ketamine would significantly expand employees’ access to a uniquely promising option for refractory mental health symptoms. With conventional treatments, achievement of symptom remission is often frustratingly elusive, leaving far too many individuals to struggle with ongoing functional impairment.[1] By providing an important new avenue to recovery for those not well served by existing treatments, employers can meaningfully enhance the mental health outcomes and quality of life of some of their most vulnerable employees.

From a fiscal perspective, expanding effective access to mental health treatment is likely to prove wise investment. Inadequately treated psychiatric conditions are well-established drivers of reduced productivity, absenteeism, and increased healthcare spending.[8] Depression alone is estimated to account for over $44 billion in lost productive work time each year in the US.[9] While the upfront costs of ketamine therapy may give some employers pause, a proactive approach targeting those most in need of additional treatment options has the potential to generate substantial offsetting savings by preventing costly downstream consequences of uncontrolled symptoms, such as extended disability leaves and repeat hospitalizations. Some projections indicate that high-quality, comprehensive behavioral health benefits could yield returns of $2-4 per dollar invested.[10]

Covering ketamine therapy may also provide competitive talent acquisition and retention. Today’s job applicants increasingly expect employers to provide a thoughtful, holistic approach to benefits that goes beyond the status quo to support their wellbeing.[11] Including cutting-edge, evidence-based treatments such as ketamine demonstrate an authentic commitment to employee mental health that is likely to resonate with top candidates, especially those in high-stress fields. Particularly for safety-sensitive industries, where untreated mental illness poses enhanced risks, ketamine coverage may play a key role in attracting and retaining the most qualified personnel.

Employers considering ketamine therapy coverage should be aware of the important legal and logistical factors. While FDA-approved for depression in its esketamine formulation, IV ketamine for mental health conditions is currently an off-label use in the US, and insurance coverage remains limited.[12,13] Partnering with reputable ketamine providers and expert benefits consultants will be essential to navigate the evolving regulatory landscape, craft appropriate protocols for treatment eligibility and monitoring, and ensure compliance with all relevant state and federal laws. Investing in educational initiatives to provide employees with accurate, destigmatizing information about ketamine’s safety and efficacy when used in a supervised medical context will help allay concerns, combat misconceptions, and facilitate appropriate uptake.

Conclusions and Recommendations

Ketamine therapy has been one of the most promising and exciting new developments in mental health treatment for decades. This research unequivocally demonstrates its remarkable efficacy in rapidly alleviating symptoms of depression and other conditions that have not responded adequately to standard treatments. Therefore, it has the potential to be a uniquely valuable addition to workplace mental health benefits.

While not without challenges, in light of the profound productivity and quality-of-life costs of inadequately treated mental illness, offering ketamine therapy coverage has the potential to yield substantial returns for employers and employees alike. These benefits are likely to be particularly pronounced for those whose mental health conditions have remained refractory despite multiple conventional medication trials. A carefully designed ketamine coverage program with input from benefits experts, legal counsel, and experienced ketamine providers is well positioned to expand access to this transformative treatment while ensuring appropriate patient selection and monitoring.

As researchers continue to refine ketamine treatment protocols and document their long-term impacts, evidence supporting its use in mainstream mental health practice will likely only grow stronger. Forward-thinking employers who act now to provide cutting-edge, evidence-based treatments like ketamine for those most in need will be well positioned to support a thriving, productive workforce and establish themselves as leaders in innovative workplace mental health. When it comes to investing in employee well-being, the immensely promising ketamine therapy is an opportunity.


Kryst J, Kawalec P, Mitoraj AM, et al. Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials. Pharmacol Rep. 2020;72(3):543-562.

Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351-354.

Han Y, Chen J, Zou D, et al. Efficacy of ketamine in the rapid treatment of major depressive disorder: a meta-analysis of randomized, double-blind, placebo-controlled studies. Neuropsychiatr Dis Treat. 2016;12:2859-2867.

Popova V, Daly EJ, Trivedi M, et al. Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study. Am J Psychiatry. 2019;176(6):428-438.

Feder A, Parides MK, Murrough JW, et al. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014;71(6):681-688.

Rodriguez CI, Kegeles LS, Levinson A, et al. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology. 2013;38(12):2475-2483.

Zanos P, Moaddel R, Morris PJ, et al. Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacol Rev. 2018;70(3):621-660.

Greenberg PE, Fournier AA, Sisitsky T, Pike CT, Kessler RC. The economic burden of adults with major depressive disorder in the United States (2005 and 2010). J Clin Psychiatry. 2015;76(2):155-162.

Stewart WF, Ricci JA, Chee E, Hahn SR, Morganstein D. Cost of lost productive work time among US workers with depression [published correction appears in JAMA. 2003 Oct 22;290(16):2218]. JAMA. 2003;289(23):3135-3144.

Karg RS, Bose J, Batts KR, et al. Past Year Mental Disorders among Adults in the United States: Results from the 2008-2012 Mental Health Surveillance Study. 2014 Oct. In: CBHSQ Data Review. Rockville (MD): Substance Abuse and Mental Health Services Administration (US).

National Business Group on Health. Mental health, substance abuse, and depression: current trends in employee assistance programs and employer sponsored health plans. 2018.

Wilkinson ST, Sanacora G. Considerations on the Off-label Use of Ketamine as a Treatment for Mood Disorders. JAMA. 2017;318(9):793-794.

Zhang MW, Harris KM, Ho RC. Is off-label repeat prescription of ketamine as a rapid antidepressant safe? Controversies, ethical concerns, and legal implications. BMC Med Ethics. 2016;17:4.

Dore J, Turnipseed B, Dwyer S, et al. Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy. J Psychoactive Drugs. 2019;51(2):189-198.

Zanos P, Gould TD. Mechanisms of ketamine action as an antidepressant. Mol Psychiatry. 2018;23(4):801-811.

Pilot Course: Essential Business Foundations for Psychedelic Therapists

Join the waitlist for our pilot course today and start shaping a more effective practice.

We will never spam or sell your info. Ever.