A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department

Larkin, Gregory Luke; Beautrais, Annette L.; Turelli, R.R.; Sanacora, Gerard; Powsner, Seth M.; Lippmann, Melanie J.; Krystal, John H.

doi:10.1016/s0924-9338(11)73311-9

Cited by 36 publications

(51 citation statements)

References 18 publications

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“…[12] Furthermore, suicidal cognition was continuously eradicated for 2 weeks in ketamine responders given thrice-weekly, repeat infusions. Similar additional reports in TRD, [13] bipolar disorder, [14] and depressed patients presenting to the emergency department with suicidal ideation [15] suggest that ketamine can reduce suicidal ideation within 40 min of infusion and reductions may be maintained for up to 10 days.…”

Section: Introductionsupporting

confidence: 69%

Effects of Ketamine on Explicit and Implicit Suicidal Cognition: A Randomized Controlled Trial in Treatment-Resistant Depression

et al. 2014

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Background Preliminary evidence suggests intravenous ketamine has rapid effects on suicidal cognition, making it an attractive candidate for depressed patients at imminent risk of suicide. In the first randomized controlled trial of ketamine using an anesthetic control condition, we tested ketamine’s acute effects on explicit suicidal cognition and a performance-based index of implicit suicidal cognition (Implicit Association Test; IAT) previously linked to suicidal behavior. Method Symptomatic patients with treatment-resistant unipolar major depression (inadequate response to ≥3 antidepressants) were assessed using a composite index of explicit suicidal ideation (Beck Scale for Suicidal Ideation, Montgomery-Asberg Rating Scale suicide item, Quick Inventory of Depressive Symptoms suicide item) and the IAT to assess suicidality implicitly. Measures were taken at baseline and 24 hr following a single subanesthetic dose of ketamine (n = 36) or midazolam (n = 21), a psychoactive placebo agent selected for its similar, rapid anesthetic effects. Twenty four hours postinfusion, explicit suicidal cognition was significantly reduced in the ketamine but not the midazolam group. Results Fifty three percent of ketamine-treated patients scored zero on all three explicit suicide measures at 24 hr, compared with 24% of the midazolam group (χ2 = 4.6; P = .03). Implicit associations between self- and escape-related words were reduced following ketamine (P = .01; d = .58) but not midazolam (P = .68; d = .09). Ketamine-specific decreases in explicit suicidal cognition were largest in patients with elevated suicidal cognition at baseline, and were mediated by decreases in nonsuicide-related depressive symptoms. Conclusions Intravenous ketamine produces rapid reductions in suicidal cognition over and above active placebo. Further study is warranted to test ketamine’s antisuicidal effects in higher-risk samples.

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Section: Introductionsupporting

confidence: 69%

Effects of Ketamine on Explicit and Implicit Suicidal Cognition: A Randomized Controlled Trial in Treatment-Resistant Depression

et al. 2014

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“…None of the studies included in the current meta‐analysis documented major adverse effects, but side effects such as transient headache, dizziness and nausea were commonly reported; such side effects reportedly dissipated fairly quickly, usually once the infusion was complete (aan het Rot et al ., ; Abdallah et al ., ; Thakurta et al ., ; Murrough et al ., ). Many studies also documented the dissociative effects of ketamine in participants (Diazgranados et al ., ; Ibrahim et al ., ; Larkin et al ., ; Zarate et al ., ; Loo et al ., ; Murrough et al ., , ; Carlson et al ., ; Sos et al ., ; Lapidus et al ., ) and increased, if somewhat mild, psychotomimetic experiences (Salvadore et al ., , ; Mathew et al ., ; Larkin et al ., ; Loo et al ., ; Murrough et al ., , ; Sos et al ., ; Lapidus et al ., ). As most studies have not followed the participants beyond 24 h post infusion, any long‐term side effects and addictive potential of ketamine infusion in the treatment of depression are difficult to determine.…”

Section: Discussionmentioning

confidence: 99%

The use of ketamine as an antidepressant: a systematic review and meta‐analysis

Coyle

Laws

2015

Human Psychopharmacology

237

159

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Objective The current meta-analysis examines the effects of ketamine infusion on depressive symptoms over time in major depressive disorder (MDD) and bipolar disorder (BD). Methods Following a systematic review of the literature, data were extracted from 21 studies (n = 437 receiving ketamine) and analysed at four post-infusion time points (4 h, 24 h, 7 days and 12-14 days). The moderating effects of several factors were assessed including: repeat/single infusion, diagnosis, open-label/participant-blind infusion, pre-post/placebo-controlled design and the sex of patients. Results Effect sizes were significantly larger for repeat than single infusion at 4 h, 24 h and 7 days. For single infusion studies, effect sizes were large and significant at 4 h, 24 h and 7 days. The percentage of males was a predictor of antidepressant response at 7 days. Effect sizes for open-label and participant-blind infusions were not significantly different at any time point. Conclusions Single ketamine infusions elicit a significant antidepressant effect from 4 h to 7 days; the small number of studies at 12-14 days post infusion failed to reach significance. Results suggest a discrepancy in peak response time depending upon primary diagnosis -24 h for MDD and 7 days for BD. The majority of published studies have used pre-post comparison; further placebo-controlled studies would help to clarify the effect of ketamine over time.

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“…48,49 Up to six infusions of repeated ketamine administered once, twice, or three times per week were found to be safe and efficacious in maintaining treatment response. 22,[50][51][52][53] Other studies reported safety and efficacy using a single administration of various routes and doses of ketamine, including 0.2 mg/kg intravenous bolus, 54 50 mg intranasal, 23 and 0.5 mg/kg or 0.25 mg/kg intramuscular injection. 55…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

Ketamine as a promising prototype for a new generation of rapid‐acting antidepressants

Abdallah

Averill

Krystal

2015

Annals of the New York Academy of Sciences

102

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The discovery of ketamine’s rapid and robust antidepressant effects opened a window into a new generation of antidepressants. Multiple controlled trials and open-label studies have demonstrated these effects across a variety of patient populations known to often achieve little to no response from traditional antidepressants. Ketamine has been generally well tolerated across patient groups, with transient mild to moderate adverse effects during infusion. However, the optimal dosing and route of administration and the safety of chronic treatment is not fully known. This review summarizes the clinical effects of ketamine and its neurobiological underpinnings and mechanisms of action that may provide insight into the neurobiology of depression, relevant biomarkers, and treatment targets. Moreover, we offer suggestions for future research that can continue to advance the field forward and ultimately improve the psychopharmacologic interventions available for those individuals struggling with depressive and trauma-related disorders.

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A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department

Cited by 36 publications

References 18 publications

Effects of Ketamine on Explicit and Implicit Suicidal Cognition: A Randomized Controlled Trial in Treatment-Resistant Depression

Effects of Ketamine on Explicit and Implicit Suicidal Cognition: A Randomized Controlled Trial in Treatment-Resistant Depression

The use of ketamine as an antidepressant: a systematic review and meta‐analysis

Ketamine as a promising prototype for a new generation of rapid‐acting antidepressants

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