Mental Health, Psychiatry, Patient Interactions

Case Report: Ketamine for Treatment of Acute Suicidality

Depression and suicide have large health and economic impacts on our society — yet we lack acute treatment options and prevention methods.

We describe a case of depression and acute suicidality in a 27-year-old female patient who received larger subanesthetic doses of ketamine than prior studies. She was followed in an outpatient ketamine clinic with repeat infusions every two days for six total treatments and noted to have marked improvement and resolution of her acute suicidality.

Larger subanesthetic doses of ketamine may have greater efficacy in treating acute suicidality. Further studies should be conducted to better understand the dose-dependent impacts of ketamine on acute suicidality and depression while balancing the potential complications of its use.

Introduction
Suicide was the 12th leading cause of death in the United States in 2020, claiming the lives of 45,979 individuals.1 In 2020, at least 15.2 million adolescents and adults thought about committing suicide, 4.5 million made a suicide plan, and 1.8 million attempted suicide.2

Many suicidal ideation and attempted suicide cases are seen in the emergency department. In 2017, these cases accounted for more than 1.48 million visits, or approximately 1.1 percent of the 132 million total ED visits that year.3

In 2019, the large number of suicides and suicide attempts resulted in more than $12.8 billion in medical costs alone and more than $489 billion in composite medical costs, work loss costs, value of statistical life, and quality of life costs.4

Interventions and medications such as electroconvulsive therapy (ECT) and selective serotonin reuptake inhibitors (SSRIs) can treat depression and subsequent suicidal ideation, but these treatment therapies either require general anesthesia and extensive monitoring or take weeks to months to have significant clinical improvement and, therefore, are of minimal value in the ED.5,6

As of this publication, there is no standardized treatment for acute suicidality. Given the large health and economic impact suicide has on our society, we must prioritize finding more acute interventions for depression and suicidality. Multiple smaller trials for potential interventions for acute suicidality have been in the literature recently, but there has not been a large enough study with defined treatment protocols.

Here, we present a case of subanesthetic ketamine infusion as treatment for acute suicidality in a patient with a history of depression.

Case Report
A 27-year-old female weighing 81 kg (179 lbs) with a history of postpartum depression and major depressive disorder presented to the ED with a one-day history of acute depressive symptoms with suicidal ideation. She first developed symptoms as part of postpartum depression after giving birth to a child approximately a year ago, and her symptoms persisted. She tried outpatient treatment with citalopram 40 mg daily at the onset of her postpartum depression, but discontinued treatment secondary to the therapy making her feel “obsessive.” She also tried multiple other SSRIs, all of which were ineffective for various reasons. She subsequently presented to the ED for further evaluation and management because she felt the desire to harm herself with a defined plan of “driving a car into a pole.”

The patient’s ED evaluation was largely unremarkable except for her suicidal ideation with a defined method and plan for doing so. An order was placed for 100mg of ketamine to be infused over the course of an hour, approximately 1.23 mg/kg/hr. The patient was then observed for approximately an hour after the infusion and re-evaluated thereafter.

During the re-evaluation, the patient was found to be resting comfortably in no acute distress. She reported feeling significant symptomatic improvement and said that her suicidal ideation had resolved. The case was discussed with both the patient’s personal psychiatrist and a ketamine provider prior to the patient’s discharge, with definitive outpatient follow-up plans. She was subsequently discharged from the ED in stable condition.

Two days after the initial ED infusion, she was seen at a ketamine clinic every two days for five repeat infusions treatments over the course of 10 total days. Prior to each infusion, she was evaluated with Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) surveys, self-reported measures for depression and generalized anxiety, respectively.

The PHQ-9 is a nine-item self-reported survey consistent of criteria for major depression rated on a four-point scale (0 = not at all, 1 = several days, 2 = more than half the days, 3 = nearly every day) with a sensitivity of 77 percent and specificity of 85 percent for major depression when using a 10-point cutoff.7

The GAD-7 is a seven-item self-reported survey consistent of criteria for generalized anxiety rated on a four-point scale (0 = not at all, 1 = several days, 2 = more than half the days, 3 = nearly every day) with a sensitivity of 83 percent and specificity of 84 percent for generalized anxiety disorder when using an eight-point cutoff.8

Ketamine infusions were titrated up from 90mg to 115mg of ketamine to be infused over the course of 45 minutes, approximately 1.48mg/kg/hr to 1.89mg/kg/hr. The patient was given ondansetron, metoclopramide, midazolam, and/or phenergan as pre-treatment antiemetics. Her vital signs were monitored and were stable throughout the entirety of each infusion treatment, and no adverse events were noted. During her 10-day treatment course, she was noted to have marked improvement in measures of depression and generalized anxiety, as seen in Table 1. After the fifth infusion, the patient was discharged with a prescription for 100mg ketamine lozenges to be taken once a night and instructions to return to the clinic for booster treatments as needed.

Table 1

Days after initial infusion

2

4

6

8

10

PHQ-9

24

3

2

1

2

GAD-7

16

6

3

3

4

Note: PHQ-9 = Patient Health Questionnaire; GAD-7 = Generalized Anxiety Disorder

Discussion
Ketamine is a N-methyl-D-aspartic acid (NMDA) glutamate receptor antagonist that has a proposed mechanism action of increasing synaptogenesis and elevating levels of brain-derived neurotrophic factor (BDNF), which has shown promise as a potential treatment of acute suicidality and depression.9 However, recent studies have shown variable dose-dependent effects of ketamine on acute suicidality and depression in weakly powered trials.10-14 Prior studies have primarily used subanesthetic doses of ketamine ranging from 0.2-0.5mg/kg, with lower doses being less likely to show statistically significant impact on reducing depression and acute suicidality.11,13-15 In studies that have shown significant impact, the effects take peak effect after approximately one hour and last from a few hours to a few days with diminishing effects after a few hours.11,13-15

While the potential positive impacts of ketamine are of interest in treating acute suicidality and depression, there are multiple contraindications to its use: underlying conditions in which elevated blood pressure may incur complications (e.g., aortic dissection, uncontrolled hypertension, myocardial infarction, and aneurysms); schizophrenia, as it may exacerbate the underlying condition; acute alcohol intoxication, as it may cause additive sedative effects; and pregnancy and breastfeeding, as its effects on fetuses and infants are not clearly elucidated at this time.9

Given the limited scale and number of studies looking at the use of ketamine infusion for acute suicidality and depression treatment thus far, there are several limitations for its use in the ED.

First, there has not been a sufficiently powered study that provides optimal dosing and alternatives to ketamine and, similar to other interventions, there is a possibility that patients will not respond to the infusion.10 Some studies suggest that this may be secondary to insufficient dosing and that patients may benefit from a higher-dose infusion.12,14,15 While there are increased odds of encountering potential adverse effects when using higher doses of ketamine such as laryngospasm, respiratory depression, apnea, and emesis, these were not present in the our case.9These effects can be minimized by avoiding rapid IV administrations as done during procedural sedation or rapid sequence intubation, and prolonging it over the course of an hour and closely monitoring patients and intervening as necessary.9

Another limitation of ketamine infusion is that it may need to be repeated after a few days or weeks, as its effect diminishes over time.16 However, similar to other chief complaints like wound care where initial treatment and management of acute exacerbations are done in the ED, ketamine infusion therapy can be utilized in the ED for acute suicidality and depression during initial encounters and acute exacerbations and can otherwise be deferred and managed in outpatient settings if resources are available.

Finally, as there are multiple potential contraindications for ketamine, it is imperative to complete a comprehensive history and physical prior to infusion administration to minimize potential harm.17

While a single case is insufficient to demonstrate a causative relationship between high-dose ketamine infusion and resolution of acute suicidality and depression, the effects appear similar to the lower-dose trials seen thus far, and high-dose ketamine infusion may be useful as a potential treatment during acute exacerbations.10,13,14

However, prior to widespread implementation of the practice, further studies should be done in a prospective manner to more clearly delineate the dose-dependent impact of ketamine on acute suicidality and depression, and to minimize the potential for adverse events.

Conclusion
Depression and suicidality are common presenting complaints in the ED and require vast resources to fully evaluate, treat, and determine appropriate dispositions for patients. Our case illustrates how subanesthetic-dose ketamine infusion may be used to treat refractory depression and acute suicidality.

As there is a greater risk for adverse events with higher-dose ketamine, patients should be monitored closely and intervened upon in case adverse events occur. After treatment in the acute phase, patients should follow up outpatient with psychiatry and/or ketamine clinics if possible and return to the emergency department as needed for acute exacerbations or inability to follow up on an outpatient basis.


References

  1. 2020 Web-based Injury Statistics Query and Reporting System (WISQARS) Data Visualization. Centers for Disease Control and Prevention. https://wisqars.cdc.gov/data/lcd/home. Accessed October 24, 2022.
  2. Key substance use and mental health indicators in the United States: Results from the 2020 national survey on drug use and health. National Alliance For Drug Endangered Children. https://nationaldec.org/resourcelibrary/key-substance-use-and-mental-health-indicators-in-the-united-states-results-from-the-2020-national-survey-on-drug-use-and-health/. Accessed October 26, 2022.
  3. Owens PL, McDermott KW, Lipari RN, Hambrick MM. Emergency Department Visits Related to Suicidal Ideation or Suicide Attempt, 2008–2017. In: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Rockville (MD): Agency for Healthcare Research and Quality (US); September 8, 2020.
  4. Peterson C, Miller GF, Barnett SB, Florence C. Economic Cost of Injury — United States, 2019. MMWR Morb Mortal Wkly Rep 2021;70:1655–1659. DOI: http://dx.doi.org/10.15585/mmwr.mm7048a1.
  5. Yoldi-Negrete M, Gill LN, Olivares S, Lauzière A, Désilets M, Tourjman SV. The effect of continuation and maintenance electroconvulsive therapy on cognition: A systematic review of the literature and meta-analysis. J Affect Disord. 2022;316:148-160. doi:10.1016/j.jad.2022.08.005
  6. Taylor MJ, Freemantle N, Geddes JR, Bhagwagar Z. Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis. Arch Gen Psychiatry. 2006;63(11):1217-1223. doi:10.1001/archpsyc.63.11.1217
  7. Manea L, Gilbody S, McMillan D. A diagnostic meta-analysis of the Patient Health Questionnaire-9 (PHQ-9) algorithm scoring method as a screen for depression. Gen Hosp Psychiatry. 2015;37(1):67-75. doi:10.1016/j.genhosppsych.2014.09.009
  8. Plummer F, Manea L, Trepel D, McMillan D. Screening for anxiety disorders with the GAD-7 and GAD-2: a systematic review and diagnostic metaanalysis. Gen Hosp Psychiatry. 2016;39:24-31. doi:10.1016/j.genhosppsych.2015.11.005
  9. Rosenbaum SB, Gupta V, Patel P, Palacios JL. Ketamine. In: StatPearls. Treasure Island (FL): StatPearls Publishing; November 24, 2022.
  10. Maguire L, Bullard T, Papa L. Ketamine for acute suicidality in the emergency department: A systematic review. Am J Emerg Med. 2021;43:54-58. doi:10.1016/j.ajem.2020.12.088
  11. Domany Y, Shelton RC, McCullumsmith CB. Ketamine for acute suicidal ideation. An emergency department intervention: A randomized, double-blind, placebo-controlled, proof-of-concept trial. Depress Anxiety. 2020;37(3):224-233. doi:10.1002/da.22975
  12. Kashani P, Yousefian S, Amini A, Heidari K, Younesian S, Hatamabadi HR. The Effect of Intravenous Ketamine in Suicidal Ideation of Emergency Department Patients. Emerg (Tehran). 2014;2(1):36-39.
  13. Lee J, Narang P, Enja M, Lippmann S. Use of ketamine in acute cases of suicidality. Innov Clin Neurosci. 2015;12(1-2):29-31.
  14. Shamabadi A, Ahmadzade A, Hasanzadeh A. Ketamine for suicidality: An umbrella review. Br J Clin Pharmacol. 2022;88(9):3990-4018. doi:10.1111/bcp.15360
  15. Ballard ED, Ionescu DF, Vande Voort JL, et al. Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety. J Psychiatr Res. 2014;58:161-166. doi:10.1016/j.jpsychires.2014.07.027
  16. Phillips JL, Norris S, Talbot J, et al. Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial. Am J Psychiatry. 2019;176(5):401-409. doi:10.1176/appi.ajp.2018.18070834
  17. Nichols KA, Paciullo CA. Subdissociative Ketamine Use in the Emergency Department. Adv Emerg Nurs J. 2019;41(1):15-22. doi:10.1097/TME.0000000000000222

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