All Suicidal Ideation Is Not Created Equal: Two Cases of Suicide Attempts During Maintenance Ketamine Treatment
Publication: American Journal of Psychiatry
to the editor: In randomized controlled trials, ketamine has been shown to rapidly decrease suicidal ideation in patients (1, 2). However, even when suicidal ideation improves with ketamine treatment, patients remain at relatively high risk of suicide attempts. Indeed, follow-up of esketamine studies revealed three cases of completed suicide (3). Here, we report on two patients who attempted suicide during maintenance treatment with intranasal racemic ketamine at our clinic.
Case 1
A 56-year-old man with severe treatment-resistant depression since age 19 and several suicide attempts by overdose and carbon monoxide poisoning underwent multiple antidepressant trials, ECT, and transcranial magnetic stimulation. After one intravenous ketamine infusion (1 mg/kg), his depressive symptoms remitted, and he successfully transitioned to maintenance treatment of 60 mg of intranasal ketamine every other day for 2 years, with no suicidal ideation. Stressful life events (family members’ deaths and a deteriorating marriage) contributed to a sudden worsening of the patient’s symptoms. An increased ketamine dose with confirmed adherence, antidepressant adjustments, and psychosocial interventions were unsuccessful, and the patient died by suicide (carbon monoxide poisoning).
Case 2
A 35-year-old woman with severe treatment-resistant depression, anxiety, and posttraumatic stress disorder (PTSD) since age 14 had a prior suicide attempt by hanging and a 6-year current depressive episode. She began intranasal ketamine treatment as an adjunct to 300 mg/day of bupropion and 225 mg/day of venlafaxine, with relief of depression and PTSD symptoms, and she continued treatment of 200 mg of intranasal ketamine every other day for 17 months. Without any reported triggering event, she discontinued ketamine for a week and attempted suicide by overdose. After hospitalization, she restarted intranasal ketamine plus antidepressant medications and has been in remission for 8 months.
Intranasal ketamine can be efficacious for patients with treatment-resistant depression and suicidal ideation. In the past 3 years at our clinic, we have treated more than 70 patients, and 33 patients currently are on maintenance treatment. Both patients described above experienced an early, robust response to ketamine, maintained for 1 to 2 years. Although the second patient might have experienced a rebound effect or withdrawal from abrupt discontinuation, the first patient was compliant, with adherence verified by family members.
Ketamine may improve factors associated with suicidal ideation, such as hopelessness; however, different types of suicidal ideation may arise in the same patient. Multiple risk factors for suicide attempt are stable (e.g., prior attempts or trait impulsivity), while others fluctuate over time, and only some are targeted by ketamine. We have limited safety data on long-term ketamine use, such as data on tolerance, withdrawal, and possible risks associated with discontinuation. In our experience, tolerance is rare, even after years of treatment. Our patients, who were severely depressed and chronically suicidal and had symptoms that did not respond to treatment, did not exhibit withdrawal or cravings upon discontinuation but returned to baseline severity. Clinicians with patients on ketamine should nonetheless remain vigilant, and clinicians should closely monitor patients for signs of nonadherence and depression or recurrence of suicidal ideation.
References
1.
Grunebaum MF, Galfalvy HC, Choo TH, et al: Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial. Am J Psychiatry 2018; 175:327–335
2.
Wilkinson ST, Ballard ED, Bloch MH, et al: The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. Am J Psychiatry 2018; 175:150–158
3.
US Food and Drug Administration (FDA): FDA briefing document: Psychopharmacologic Drugs Advisory Committee (PDAC) and Drug Safety and Risk Management (DSaRM) Advisory Committee meeting. Feb 12, 2019 (https://www.fda.gov/media/121376/download)
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Accepted: 26 August 2019
Published online: 1 February 2020
Published in print: February 01, 2020
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Dr. Cusin has received speaking and consulting fees from Alkermes, Boehringer Ingelheim, Janssen, and Takeda, and she is named as an inventor on a patent (Acyclic cucurbit[N]uril type molecular containers to treat intoxication and decrease relapse rate in substance abuse disorders). Dr. Sakurai has received manuscript or speakers honoraria from Eli Lilly, Meiji Seika, Mitsubishi Tanabe, Otsuka, Sumitomo Dainippon, and Yoshitomi Yakuhin, and he receives support from the Japanese Society of Clinical Neuropsychopharmacology and the Uehara Memorial Foundation. Dr. Fava has received research support from, has served as an adviser or consultant to, has had speaking or publishing roles for, and/or has equity in Abbott, Acadia, Adamed, Advanced Meeting Partners, Affectis, Alkermes, Amarin, American Cyanamid, the American Society of Clinical Psychopharmacology, APA, Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Avanir, Axsome, Bayer, Belvoir Media Group, Best Practice Project Management, Biogen, Biohaven, BioMarin, BioResearch, Biovail, BioXcel Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, the Brain and Behavior Research Foundation, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Cerecor, Clarus Funds, Clexio Biosciences, Clintara, the CME Institute, CNS Response, Compellis, Covance, Covidien, Cypress, DiagnoSearch Life Sciences, Dov, Edgemont, Eisai, Eli Lilly, EnVivo, ePharmaSolutions, Epix, Euthymics Bioscience, Fabre-Kramer, Forest, Forum, Ganeden, Genomind, GlaxoSmithKline, Grünenthal, the Harvard Clinical Research Institute, Hoffmann–La Roche, ICON, Imedex, Indivior, Ingenix, Intracellular, Janssen, Jazz, the Jed Foundation, Johnson & Johnson, Knoll, Labopharm, Lichtwer, Lorex, Lundbeck, Marinus, the Massachusetts General Hospital Psychiatry Academy, MedAvante, Merck, MSI Methylation Sciences, the National Alliance for Research on Schizophrenia and Depression, the National Center for Complementary and Alternative Medicine, the National Coordinating Center for Integrative Medicine, Naurex, Navitor, Nestle Health Sciences, Neuralstem, Neuronetics, NeuroRx, NextWave, NIDA, NIMH, Novartis, Nutrition 21, Orexigen, Organon, Osmotica, Otsuka, PamLab, Pfizer, Pharmacia-Upjohn, Pharmaceutical Research Associates, Pharmastar, Pharmavite, PharmoRx Therapeutics, Pharmaceutical Product Development, Photothera, Polaris, Praxis Precision Medicines, Precision Human Biolaboratory, Prexa, PsychoGenics, PsyBrain, Psylin, PThera, Purdue, Puretech Ventures, RCT Logic, Reckitt Benckiser, Relmada, Rexahn, Ridge Diagnostics, Roche, Sanofi-Aventis, Schering-Plough, Sepracor, Servier, Shenox, Shire, Solvay, Somaxon, Somerset, the Stanley Medical Research Institute, Sumitomo Dainippon, Sunovion, Supernus, Synthélabo, Taisho, Takeda, Tal Medical, Tetragenex, Teva, Transcept, TransForm, United BioSource, the Usona Institute, Vanda, Versant, VistaGen, and Wyeth-Ayerst; he is named as an inventor on patents for sequential parallel comparison design, licensed by Massachusetts General Hospital to Pharmaceutical Product Development; he is named as an inventor on patents for the pharmacogenomics of depression treatment with folate; he is named as an inventor on a patent application for a combination of ketamine plus scopolamine in major depressive disorder, licensed by Massachusetts General Hospital to Biohaven; he holds copyright for the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire, the Sexual Functioning Inventory, the Antidepressant Treatment Response Questionnaire, the Discontinuation-Emergent Signs and Symptoms inventory, the Symptoms of Depression Questionnaire, and the SAFER criteria for clinical trials and research; and he has received royalties from Lippincott Williams & Wilkins for the book Natural Medications for Psychiatric Disorders: Considering the Alternatives. Dr. Mischoulon has received research support from Nordic Naturals; he has provided unpaid consulting for Gnosis USA and Pharmavite; he has received speakers honoraria from Blackmores, the Massachusetts General Hospital Psychiatry Academy, and PeerPoint Medical Education Institute; and he has received royalties from Lippincott Williams & Wilkins for the book Natural Medications for Psychiatric Disorders: Considering the Alternatives. Dr. Bentley, Dr. Pedrelli, and Dr. Foster report no financial relationships with commercial interests.
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