Abstract

Since 2020 there has been an expansion in the number of studies highlighting the positive effect that Ketamine for Non-Anesthetic Indications (KNAI) can have on patients suffering with mental health disorders. Medicaid programs cover a large community of patients that face significant health disparities and suffer more frequently from mental health conditions. Many of these conditions are exacerbated due to socioeconomic stressors, lack of access to care, and poor support systems. Our case study focuses on 289 Medicaid-eligible patients and the effect ketamine treatment had on their mental health symptoms. These participants had an established diagnosis of Generalized Anxiety Disorder (GAD), Major Depressive Disorder (MDD) and/or Post Traumatic Stress Disorder (PTSD) prior to beginning treatment. The GAD-7, PHQ-9, and PCL-5 surveys were utilized for assessment of symptomatology in this cohort of patients. These instruments were all deployed prior to beginning treatment and at the end of the six-session Induction Series of ketamine treatments. The comparison of scores on these screening instruments pre-and post-treatment demonstrated a clinically significant reduction in symptomatology in the three diagnosis cohorts of patients listed above.

Keywords

Medicaid participants; Ketamine; Mental health; Ketamine for Non-Anesthetic Indications (KNAI); Healthcare access

Introduction

Ketamine has established itself as an important treatment for Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD), and Post-Traumatic Stress Disorder (PTSD) [1-19]. The first article looking at its role in managing treatment-resistant depression was published in 2000 [2]. Unfortunately, even with over twenty years of published studies, ketamine is still considered “off-label” for the treatment of most mental health conditions; this places ketamine therapy out of the financial reach of most Americans. The last ten years have seen an explosion in the number of clinics that are offering ketamine therapy for the treatment of mental health conditions and chronic pain [20-22]. Third-party payers however, have been slow to recognize the value of ketamine therapy and the role it can play in treating mental health conditions. Many private ketamine centers charge anywhere from $400-$1000 per session [23]. Our interest in studying this modality of treatment stems from the potential economic savings and public health benefits of making racemic ketamine a covered mental health service by state Medicaid programs.

In this case series, we present our data on the patients treated in our centers for MDD, GAD, and/or PTSD in 2022 with Health First Colorado (Medicaid) as their payor source. The objective of this case series is to identify if Medicaid participants had a change in their self-reported mental health surveys with ketamine treatment. Our hypothesis is that Medicaid-eligible patients can experience a significant decrease in their mental health symptoms with ketamine treatment.

Methods

Study Participants

This case series presents all patients seen at the three Klarisana Colorado centers in 2022 diagnosed with Major Depressive Disorder, Generalized Anxiety Disorder, or Post-Traumatic Stress Disorder with Health First Colorado (Medicaid) as their payor source. The data was collected and quantifiably analyzed to find statistical significance. Of the 289 patients total who finished the initial series of six ketamine sessions, 173 patients (60%) self-reported as biologically female at birth, and 116 patients (40%) self-reported as biologically male at birth. Many of these patients had more than one of the above-listed mental health diagnoses concurrently, so there may be an overlap of patients in the three cohorts of subgroup analyses. All patients received our standard treatment protocol without an additional experimental component. This is simply a retrospective review of our clinical data. The mean age of the subjects was 38 years (range 17- 64 years). More than half of the patients (n=150) had a diagnosis of major depressive disorder, (n=211) had generalized anxiety disorder, and (n=149) had PTSD.

Procedures

Patients wishing to receive ketamine therapy at one of our centers undergo a robust intake and evaluation process to ensure they are an appropriate candidate for treatment. Patients have an initial intake visit with one of our Advanced Practice Providers (APP) (nurse practitioner or physician assistant). During that visit, the clinic screens patients for any medical conditions that would preclude treatment. If necessary, we would contact outside clinicians to obtain medical records and/ or medical clearance. The APP would then determine if the patient was cleared from a behavioral health standpoint to receive ketamine based on internal guidelines, which look at whether a patient is wellconnected and/or referred by an outside mental health clinician. Patients without an established behavioral health support plan or those with high-risk factors such as having had a suicide attempt or mental health hospitalization within the last six months would then have an intake appointment with one of our behavioral health professionals for internal clearance. Klarisana does not clear patients with a history of organic psychosis or any diagnosis on the schizophrenia spectrum for treatment.

The patients cleared for treatment complete three psychological scoring instruments before and after an induction series of the six ketamine treatment sessions. Patients were administered the patient health questionnaire (PHQ-9), PTSD checklist for DSM-V (PCL5), and Generalized Anxiety Disorder scale (GAD-7) prior to the first ketamine session [24-29]. The same three instruments were administered again just before each patient’s sixth session.

Our treatment regimen consists of six ketamine sessions called the “Induction Series.” Patients start with a total dose of 1 mg/ kg with a maximum dose of 60 mg divided into two Intramuscular (IM) injections separated by 10 minutes. Subsequent sessions see a progressive dose escalation by up to 20 mg each time. The goal is to help the patient eventually attain a profound transpersonal experience that incorporates significant ego disruption [30]. We refer to this as the Psychotropic Therapeutic Response (PTR) [17]. It is important to note that at all times, the patients are responsive and able to speak with the clinicians; this underscores the fact that this setting uses ketamine in a fundamentally different way than it would be in other clinical settings such as emergency departments and operating rooms. This radically different application for ketamine has been referred to as Ketamine for Non-Anesthetic Indications (KNAI) [17]. This broad term covers the use of low-dose, sub-anesthetic ketamine for treating mental health conditions and chronic pain.

Results

We subdivided this cohort of patients with Colorado Medicaid seen in 2022 according to the diagnoses of either a) Major Depression Disorder, b) Post Traumatic Stress Disorder, and c) Generalized Anxiety Disorder. The data regarding the change in scores for each cohort is summarized in table 1. The data showing the overall response rate for each cohort are listed in Table 2.

Diagnosis Cohort	N	Assessment	Pre-Ketamine	SD	Post-Ketamine	SD	F	P	Change
Depression	150	PHQ-9	17.3	6.1	8.4	5.5	174.5	p<0.001	-51%
PTSD	149	PCL-5	48.7	15.8	23.4	16.1	186.4	p<0.001	-52%
Anxiety	211	GAD-7	14.5	4.9	6.9	4.8	262.6	p<0.001	-52%

Table 1: Psychological Screening Instrument Results by Diagnosis Cohort.

Diagnosis Cohort	N	Assessment	Improved Score	Worsened Score	Unchanged Score
Depression	150	PHQ-9	91% (137)	7% (11)	1% (2)
PTSD	149	PCL-5	92% (137)	8% (12)	0
Anxiety	211	GAD-7	91% (191)	9% (18)	1% (2)

Table 2: Response to Treatment by Diagnosis Cohort.

In the depression sub-group (PHQ-9), the mean score showed a 51% reduction from an average of 17.3 to 8.4 (F=174.5, P<0.001) (Figure 1). In this group, 137 patients (91%) had an improvement in their scores, 11patients (7%) had a worsening of their score, and two patients (2%) had no change in score.

Figure 1: PHQ-9 Pre and Post Ketamine Treatment Scores.

In the PTSD sub-group (PCL-5), patients showed a decrease in mean score from 48.7 pre-treatment to a score of 23.4 after treatment; this represents a 52% reduction (F=186.4, P<0.001).(figure 2).In this group 137 (92%) patients had an improvement in score, 12 patients (8%) had a worsening in their score.

Figure 2: PCL-5 Pre and Post Ketamine Treatment Scores.

The generalized anxiety disorder subgroup (GAD-7) showed a mean score of 14.5 pre-ketamine, which decreased to a mean score of 6.9 after ketamine treatment, representing a 52% decrease (F=262.6, P<0.001)(figure 3). In this group, 191 (91%) had an improvement in their score, 18 patients (9%) had a worsening of their score, and two patients (1%) had no change in score.

Figure 3: GAD-7 Pre and Post Ketamine Treatment Scores.

Discussion

The patients in this case series showed a robust treatment effect on symptoms of depression, anxiety, and PTSD. This treatment response is in line with previous studies looking at ketamine as a treatment for these indications [1-19]. It also provides further evidence that the intramuscular route of administration has similar effectiveness to the intravenous route of administration [4,31,32]. This report also highlights the larger public health implications that ketamine-based mental health therapies may have with regards to containing costs in the American healthcare system. The cohort of patients in this report all had Health First Colorado (Medicaid) as their payor source and showed a significant decrease in their symptomatology. Other published studies show that ketamine can reduce suicidal ideation [33- 40]. While we did not design this case series to answer this question, it does raise the possibility that increased access to ketamine-based mental health treatments in Medicaid systems across the country could translate into a decrease in suicidality in patients and fewer emergency department visits and hospital admissions.

Additionally, each diagnosis cohort saw a robust response in the percentage of patients in each cohort who had an improvement in symptoms (Table 2). One limitation of our data set is that we do not have any information as to why some of the patients had a worsening in a particular score. In reviewing those patients, some of them had improvements in one of the other scores even though one particular score may have worsened. One hypothesis is that, given that these scoring instruments show a snapshot in time, a given patient may have had other factors and/or life stressors on the day the follow up score was administered. Future research can look at adding a qualitative component to better characterize if a worsening score truly reflects worsening symptomatology or if it is a function of the circumstances of the day it is administered.

This data is important given the number of people who qualify for state Medicaid programs nationwide. In February 2023, 29.8% of all Coloradans reported having either symptoms of anxiety and/or depression [41]. This number rapidly increased due to the stressors that occurred during the COVID-19 pandemic. Colorado’s average suicide rate is 8.7% higher than the U.S. national average, with 17.4% of children reporting needing mental health services and not being able to obtain those [41]. This demographic that continues to face challenges accessing health care services is typically underrepresented and has a low socioeconomic status. These demographic groups often face disparities in receiving adequate mental health services with fears of discrimination, stigma, and financial debt [42]. The expansion of Medicaid led to 4 million new eligible participants, with nearly 60% being people of color [43]. As there are over twenty years of published studies supporting the use of ketamine for mental health conditions, one can raise an important ethical question of why this therapy is not being made accessible to patients with Medicaid as their payor source. This population has a disproportionate number of minorities and other disadvantaged people who do not have the financial means to pay for ketamine treatment out of pocket [44-45]. Although these participants qualify for Medicaid, they are often under-represented, which inadvertently can lead to poorer health outcomes. In order to mitigate the barrier this population faces, more mental health services must be available.

When one looks at whether access to ketamine-based treatments for Medicaid patients can improve health and decrease costs, it is crucial to have some context on Medicaid. Currently, there are 1,563,8445 Coloradans covered by Medicaid [46]. There is clear evidence that access to mental health services and mental health clinicians allows patients to be treated in outpatient settings, which helps reduce unnecessary emergency department visits [47]. Increased services showed improved compliance with care and easier access to medication, especially for those needing psychiatric care [48]. There are financial incentives for state governments to consider when there are adequate mental health services. With the federal funding to states dropping, there has never been a more critical time to find effective solutions for the rapidly escalating numbers of people suffering from mental illness [49]. Studies completed by the Department of Corrections indicate a $10 million saving for inpatient hospitalization in the first year of Medicaid expansion related to providing preventative mental health services in outpatient settings [47]. Reducing hospital admissions expenditures can decrease the accumulation of unforeseen medical debt. Overall, the first two years of implementing Medicaid expansion reduced $3.4 billion of medical debt sent to collections [50]. This government-funded healthcare program supported the reduction of unnecessary healthcare expenditure, which impacts patients’ financial well-being.

Conclusion

While this current report does not address the longitudinal component of whether this cohort of patients had decreased emergency department visits and hospital admissions, we plan on a follow-up study that will look at these data points in the year after they finish treatment. Taken against the backdrop of the large body of evidence supporting the use of ketamine therapy for mental health indications, our snapshot of data in this cohort of Medicaid patients highlights the potential public health benefits of government payors offering mental health therapies utilizing racemic ketamine to their members. We are encouraged that there has also been some early acceptance by private companies to offer ketamine as a direct benefit to employees [51,52]. We would recommend further research focusing on the cost savings that could occur with ketamine therapy covered under a government healthcare program. Additional research should focus on government funded healthcare programs increasing access to mental health services such as ketamine therapy.

References

1. Albott CS, Lim KO, Forbes MK, Erbes C, Tye SJ, et al. (2018) Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression. J Clin Psychiatry 79. [Ref.]
2. Berman RM, Cappiello A, Anand A, Heninger GR, Charney DS, et al. (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47: 351-354. [Ref.]
3. Castle C, Gray A, Neehoff S, Glue P (2017) Effect of ketamine dose on self-rated dissociation in patients with treatment refractory anxiety disorders. J Psychopharmacol 31: 1306-1311. [Ref.]
4. Dore J, Turnipseed B, Dwyer S, Turnipseed Feder A, Costi S, Rutter SB, Collins AB, Govindarajulu U, et al. (2021) A
   Randomized Controlled Trial of Repeated Ketamine Administration for
   Chronic Posttraumatic Stress Disorder. Am J Psychiatry 178: 193-202.A, Andries J, et al. (2019) Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy. J Psychoactive Drugs 51: 189-198. [Ref.]
5. Hietamies TM, L McInnes A, Klise AJ, Worley MJ, Qian JJ, et al. (2023) The effects of ketamine on symptoms of depression and anxiety in real-world care settings: A retrospective controlled analysis. J Affect Disord 335: 484-492. [Ref.]
6. Feder A, Parides MK, Murrough JW, Perez AM, Morgan JE, et al. (2014) Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry 71: 681-688. [Ref.]
7. Feder A, Costi S, Rutter SB, Collins AB, Govindarajulu U, et al. (2021) A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. Am J Psychiatry 178: 193-202. [Ref.]
8. Glue P, Medlicott NJ, Harland S, Neehoff S, Fahey BA, et al. (2017) Ketamine’s dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders. J Psychopharmacol 31: 1302-1305. [Ref.]
9. Glue P, Neehoff SM, Medlicott NJ, Gray A, Kibby G, et al. (2018) Safety and efficacy of maintenance ketamine treatment in patients with treatment-refractory generalised anxiety and social anxiety disorders. J Psychopharmacol 32: 663-667. [Ref.]
10. Glue P, Neehoff S, Sabadel A, Broughton L, Nedelec ML, et al. (2020) Effects of ketamine in patients with treatment-refractory generalized anxiety and social anxiety disorders: Exploratory double-blind psychoactive-controlled replication study. J Psychopharmacol 34: 267-272. [Ref.]
11. Krystal JH, Abdallah CG, Sanacora G, Charney DS, Duman RS (2019) Ketamine: A Paradigm Shift for Depression Research and Treatment. Neuron 101: 774-778. [Ref.]
12. McGhee LL, Maani CV, Garza TH, Gaylord KM, Black IH (2008) The correlation between ketamine and posttraumatic stress disorder in burned service members. J Trauma 64: S195-S198. [Ref.]
13. McIntyre RS, Lipsitz O, Rodrigues NB, Lee Y, Cha DS, et al. (2020) The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder. Bipolar Disord 22: 831-840. [Ref.]
14. Norbury A, Rutter SB, Collins AB, Costi S, Jha MK, et al. (2021) Neuroimaging correlates and predictors of response to repeateddose intravenous ketamine in PTSD: preliminary evidence. Neuropsychopharmacol 46: 2266-2277. [Ref.]
15. Phillips JL, Norris S, Talbot J, Birmingham M, Hatchard T, et al. (2019) Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial. Am J Psychiatry 176: 401-409. [Ref.]
16. Larkin GL, Beautrais AL (2017) A Preliminary Naturalistic Study of Low-Dose Ketamine for Depression and Suicide Ideation in the Emergency Department. Int J Neuropsychopharmacol 20: 611. [Ref.]
17. Ross C, Rakesh J, Bonnett CJ, Wolfson P (2019) High-dose ketamine infusion for the treatment of posttraumatic stress disorder in combat veterans. Ann Clin Psychiatry 31: 271-279. [Ref.]
18. Taylor JH, Landeros-Weisenberger A, Coughlin A, Mulqueen J, Johnson JA, et al. (2018) Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial. Neuropsychopharmacol 43: 325-333. [Ref.]
19. Tully JL, Dahlen AD, Haggarty CJ, Schiöth HB, Brooks S (2022) Ketamine treatment for refractory anxiety: A systematic review. Br J Clin Pharmacol 88: 4412-4426. [Ref.]
20. Peskin E, Gudin J, Schatman ME (2023) Increased Demand for Ketamine Infusions and Associated Complexities. J Pain Res 16: 295- 299. [Ref.]
21. Busby M (2023) Ketamine clinics have emerged across the US. They’re already going bust. The Guardian. [Ref.]
22. Dunn L, Snow K (2023) Ketamine clinics for mental health are popping up across the U.S. Does the treatment work? NBC News (online). [Ref.]
23. Newberry L (2023) The legal psychedelic: Ketamine is a fast-acting treatment for depression (if you have the money). Los Angeles Times (online). [Ref.]
24. Blevins CA, Weathers FW, Davis MT, Witte TK, Domino JL (2015) The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): Development and Initial Psychometric Evaluation. J Trauma Stress 28: 489-498. [Ref.]
25. Bovin MJ, Marx BP, Weathers FW, Gallaghar MW, Rodriguez P, et al. (2016) Psychometric properties of the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (PCL-5) in veterans. Psychol Assess 28: 1379-1391. [Ref.]
26. Kroenke K, Spitzer RL, Williams W (2001) The Patient Health Questionnaire (PHQ-9)-Overview. J Gen Intern Med 16: 606-613. [Ref.]
27. Kroenke K, Spitzer RL (2002) The PHQ-9: A new depression diagnostic and severity measure. Psychiatric Annals 32: 509-515. [Ref.]
28. Löwe B, Decker O, Müller S, Brahler E, Schellberg D, et al. (2008) Validation and standardization of the Generalized Anxiety Disorder Screener (GAD-7) in the general population. Med Care 46: 266-274. [Ref.]
29. Spitzer RL, Kroenke MD, Janet BW, Lowe B (2006) A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med 166: 1092-1097. [Ref.]
30. Wolfson PE (2014) Ketamine-Its History, Uses, Pharmacology, Therapeutic Practice and an Exploration of its Potential as Novel Treatment for Depression. I J Transpersonal Stud 33: 33-39. [Ref.]
31. Tsang VWL, Tao B, Dames S, Walsh Z, Kryskow P (2023) Safety and tolerability of intramuscular and sublingual ketamine for psychiatric treatment in the Roots To Thrive ketamine-assisted therapy program: a retrospective chart review. Ther Adv Psychopharmacol 13. [Ref.]
32. Bonnett CJ, Jain R, Ross CN, Wallington DA, Schock TR (2021) Intramuscular Ketamine to Treat Major Depressive Disorder: A Case Series of Forty Patients. J Psychiatry Ment Health 6: 1-4. [Ref.]
33. Phillips JL, Norris S, Talbot J, Hatchard T, Ortiz A, et al. (2020) Single and repeated ketamine infusions for reduction of suicidal ideation in treatment-resistant depression. Neuropsychopharmacol 45: 606- 612. [Ref.]
34. Grunebaum, MF, Galfalvy HC, Choo TH, Keilp JG, Moitra VK, et al. (2018) Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial. Am J Psychiatry 175: 327-335. [Ref.]
35. Murrough JW, Soleimani L, DeWilde KE, Collins KA, Lapidus KA, et al. (2015) Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial. Psychol Med 45: 3571-3580. [Ref.]
36. Abbar M, Demattei C, El-Hage W, Llorca PM, Samalin L, et al. (2022) Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial. BMJ 376: e067194. [Ref.]
37. Domany Y, Shelton RC, McCullumsmith CB (2020) Ketamine for acute suicidal ideation. An emergency department intervention: A randomized, double-blind, placebo-controlled, proof-of-concept trial. Depress Anxiety 37: 224-233. [Ref.]
38. Yanni Z, Bin Z, Yanling Z, Zheng W, Liu W, et al. (2019) A preliminary study of anti-suicidal efficacy of repeated ketamine infusions in depression with suicidal ideation. J Affect Disord 251: 205-212. [Ref.]
39. Zheng W, Zhou Y, Wang C, Lan XF, Ning YP (2023) A comparative analysis of antidepressant and anti-suicidal effects of repeated ketamine infusions in elderly and younger adults with depression. J Affect Disord 334: 145-151. [Ref.]
40. Phillips JL, Norris S, Talbot J, Owoeye O, Blier P (2016) PS222. Ketamine Exerts a Prolonged Reduction in Suicidal Ideation Independent of its Antidepressant Effects. I J Neuropsychopharmacol 19: 81.[Ref.]
41. Drake P, Panchel N (2023) Mental health and substance use state fact sheets. KFF. [Ref.]
42. Ngui EM, Khasakhala L, Ndetei D, Roberts LW (2010) Mental disorders, health inequalities and ethics: A global perspective. Int Rev Psychiatry 22: 235-244. [Ref.]
43. Cross-Call J, Broaddus M (2020) States That Have Expanded Medicaid Are Better Positioned to Address COVID-19 and Recession. Centre on Budget and Policy Priorities. [Ref.]
44. Lukens G, Sharer B (2020) Closing Medicaid Coverage Gap Would Help Diverse Group and Narrow Racial Disparities. Center on Budget and Policy Priorities. [Ref.]
45. McGregor B, Li C, Baltrus P, Douglas M, Hopkins J, et al. (2020) Racial and Ethnic Disparities in Treatment and Treatment Type for Depression in a National Sample of Medicaid Recipients. Psychiatr Serv 71: 663-669. [Ref.]
46. Norris L (2023) Medicaid eligibility and enrollment in Colorado. Healthinsurance.org.
47. Brown C, Fisher S, Resnick P (2016) Assessing the Economic and Budgetary Impact of Medicaid Expansion in Colora
48. Fry CE, Sommers BD (2018) Effect of Medicaid Expansion on Health Insurance Coverage and Access to Care Among Adults With Depression. Psychiatr Serv 69: 1146-1152. [Ref.]
49. Tolbert J, Ammula M (2023) 10 Things to Know About the Unwinding of the Medicaid Continuous Enrollment Provision. Medicaid. [Ref.]
50. Brevoort K, Grodzicki D, Hackmann MB (2017) Medicaid and Financial Health. National Bureau of Economic Research Working Paper 24002. [Ref.]
51. Blistein J (2022) Dr. Bronner’s Offers Employees Ketamine-Assisted Therapy. [Ref.]
52. Robinson B (2023) Ketamine-Assisted Therapy Coming Soon To An HR Department Near You. [Ref.]

Download PDF Here

 

Article Information

Article Type: CASE SERIES

Citation: Bonnett CJ, Bonder J, Jain R, Stabbert A, Sayre C (2023) Improvement of Mental Health Symptoms in Response to Ketamine Therapy in Medicaid-Eligible Patients. J Psychiatry Ment Health 8(1): dx.doi.org/10.16966/2474-7769.151

Copyright: © 2023 Bonnett CJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication history: 

Received date: 10 Jun, 2023

Accepted date: 24 Jun, 2023

Published date: 30 Jun, 2023