Intravenous Ketamine as a Treatment Option for Patients Presenting to the ED With Suicidal Ideation

Suicide is the 10th leading cause of death in the United States and the second leading cause of death among individuals ages 10 to 34 (1). Moreover, the rate of annual emergency department (ED) visits in the United States related to suicidal thoughts has nearly doubled over the last few years, with an annual average of 1.5 such visits per 1,000 ED visits (2, 3). Inpatient hospitalization, a key tool in the treatment of patients with suicidal behaviors, is a service that is in high demand, with inadequate supply (4, 5). Moreover, psychotropic medications, psychotherapy, and psychosocial interventions can take weeks or longer before they are effective. Thus inpatient psychiatric hospitalization is often necessary to allow these treatments time to have an effect.

Intravenous ketamine has been shown to produce a rapid reduction in suicidal thinking among some depressed patients after a single infusion, with peak effects coming hours after administration and persisting for up to a week, as assessed by clinician-administered measures (6). Additionally, research suggests that this effect may be independent of improvement in depressive symptoms (6). Ketamine has also been shown to be an emerging treatment option for some patients who present to the ED with suicidal thoughts (7). In one study, patients given ketamine infusions had significant decreases in Beck Scale for Suicide Ideation scores 90–180 minutes after infusion, with less robust but still present decreases 14 days after administration (7).

With the ongoing shortage of inpatient psychiatric beds in the United States, intravenous ketamine infusion may represent a potential treatment option for reducing the risk of attempted or completed suicide among patients who present to hospital EDs. Here, we present the case of a young man who came to the ED with suicidal ideation and a plan to harm himself. A single ketamine infusion was administered in the ED, after which the patient experienced a resolution of suicidal thoughts and was referred for rapid outpatient mental health follow-up treatment. This case report presents a model for the potential utilization of intravenous ketamine infusions for patients who present to the ED with depression and suicidal thinking. The patient consented to the publication of this case report. Identifying information has been omitted or otherwise altered to preserve confidentiality.

Case

Mr. B was a 33-year-old male with a psychiatric history of depression, anxiety, and attention-deficit hyperactivity disorder who presented to the ED with increased depression and a plan to complete suicide. His medications included daily doses of escitalopram 20 mg, lisdexamfetamine 40 mg, and hydroxyzine 25 mg. During the initial psychiatric evaluation, pertinent history included no past inpatient psychiatric hospitalizations, multiple failed antidepressant trials, a family history of depression, no history of suicide attempts, and no access to firearms. Additionally, the patient reported that he had a history of cannabis, cocaine, alcohol, and hallucinogen use. Notably, for 6 months prior to ED presentation he had abstained from all substances.

Mr. B reported a 6-week progressive worsening of his depressive symptoms and development of suicidal thoughts. His thoughts of suicide included a plan for asphyxiation via helium, and prior to presentation he had gone to a local store to acquire the items needed to complete his plan. Mr. B became distressed by these thoughts and reached out to a friend for help.

On the basis of medical and psychiatric evaluations, it was determined that Mr. B had treatment-refractory depression, having failed multiple antidepressant trials. Treatment with intravenous ketamine was discussed, and the patient gave informed consent. Mr. B had no history of previous ketamine or esketamine use. Per protocol, a single intravenous infusion of ketamine at 0.5 mg per kg was administered over 40 minutes. After the treatment, Mr. B self-reported significant improvement in his depressive symptoms and resolution of suicidal ideation, and after a period of observation, he requested discharge. At this time, safety planning and coordination with the patient’s roommate were completed. Mr. B was discharged home, instructed to follow up with a psychiatrist for an intake within 48 hours, and provided with criteria to seek emergency mental health care should his suicidal thoughts return.

Mr. B attended his intake appointment as scheduled and reported sustained improvement of his depression and an absence of suicidal ideation. On day 4 postinfusion, in accordance with his safety plan, Mr. B called his psychiatrist to report an increase in depressive symptoms with passive suicidal ideation. He reported that his depression was less severe than preinfusion levels and that he did not have a plan or an intent to attempt suicide. He met with his psychiatrist as scheduled the next week, at which time he continued to report depression but no plan or intent related to his suicidal ideation. Over the next few months, Mr. B established care with an outpatient psychotherapist and overall reported improvement. He remained off psychotropic medications, with the exception of the above-noted stimulant, for several months before reinitiating and stabilizing on his previous regimen of escitalopram 20 mg. He did not require inpatient psychiatric hospitalization and continued to engage actively in outpatient treatment.

Discussion

ED administration of intravenous ketamine infusions could emerge as an important treatment tool for a select group of patients with suicidal thoughts and behaviors for whom traditional treatment options may not be available. The proposed protocol utilized in this case was based largely on the administration methods used in research published by the Yale New Haven Psychiatric Hospital and may represent a standard dosing regimen for therapeutic ketamine infusions (8). Ketamine offers several potential advantages over traditional treatment options and has a favorable pharmacological safety profile. Its potential benefits include a rapid reduction in depressive symptoms and suicidal thoughts, the potential to avoid unnecessary inpatient psychiatric hospitalization, and decreased utilization of EDs as holding areas for patients awaiting improvement in their symptoms or inpatient hospitalization. Careful patient selection, close monitoring, and strict exclusionary criteria improve the safety profile of this medication. Hypertension, substance use disorders, current psychotic symptoms, pregnancy, and comorbid medical illnesses are frequently used as exclusion criteria in ketamine research. These conditions should be considered as possible contraindications for treatment to help improve the safety profile (8–10). In this case, Mr. B’s history of substance use disorder was considered, because active substance use is an exclusionary criterion in the protocol utilized. However, because the patient had no substance use within the past 6 months, his substance use disorder was classified as “in early remission.” Additionally, there is emerging evidence that therapeutic ketamine doses have low addictive—and potential antiaddictive—properties (11). Furthermore, ketamine’s S-enantiomer, esketamine, which is approved by the Food and Drug Administration for treatment-resistant depression and major depressive disorder with suicidal ideation, does not carry an absolute contraindication of substance use disorder. Given these considerations, after a careful risk-benefit analysis, we determined that there was an appreciably greater risk of self-harm without ketamine administration, compared with the risk of relapse with ketamine; thus we elected to proceed with the treatment.

This case report highlights a novel treatment approach of an ED infusion of a subanesthetic dose of ketamine for suicidal thinking, with a robust and comprehensive plan for transition to outpatient mental health treatment. Although many patients experience improvement in depressive symptoms and suicidal thoughts following ketamine infusion, the duration of this effect appears to vary among individual patients (6, 8). Moreover, to our knowledge, none of the available literature has measured rates of attempted or completed suicide following ketamine infusions. In the aforementioned protocol, rapid patient connection to outpatient treatment is considered an essential safety measure, given the uncertainty around the timing of symptom relief in suicidal thinking and the possibility of self-harm. Additionally, the authors of the protocol proposed monitoring for adverse reactions to ketamine or nonresponse for a minimum of 2 hours from the start of a ketamine infusion to assess response.

When considering possible discharge for a patient who presents with suicidal thinking, special attention should be paid to safety planning and a thorough assessment of both risk factors for self-harm (e.g., previous suicide attempts, access to firearms, preparatory behavior, and acute psychosocial stressors) and mitigation strategies to reduce this risk. In the case of Mr. B, discharge presented an appreciable risk, which made the aforementioned strategies a critical part of a safe discharge plan. This was illustrated when his connection to an outpatient treatment provider and his ability to utilize previously discussed safety planning allowed him to seek out assistance when depression with passive suicidal thoughts returned 4 days after his ketamine infusion.

Although this case represents a successful implementation of this protocol, future research is needed to determine whether a single ketamine infusion is an effective and safe intervention for patients who present to the ED with depression and suicidal ideation. Additional research is needed into the duration and quality of the reduction in suicidal thinking that has been attributed to ketamine.

Key Points/Clinical Pearls