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Safety of Repeated Administration of Parenteral Ketamine for Depression

David Feifel, David Dadiomov, Kelly C. Lee

Pharmaceuticals July 13, 2020 DOI: 10.3390/ph13070151 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Survey and literature review Peer reviewed
Sample size 6,630
Population Patients with depression treated with repeated parenteral ketamine, as reported by providers and in published studies
Intervention Parenteral ketamine
Topics Depression Esketamine Ketamine
Key findings Adverse effects requiring discontinuation of repeated parenteral ketamine for depression were uncommon: 0.7% among 6,630 patients reported by surveyed providers and 1.2% in 20 published reports. Psychological distress during treatment was the most frequent cause; bladder dysfunction, cognitive decline, and psychotic symptoms were rare. The authors suggest long-term ketamine treatment for depression is reasonably safe.

Abstract

The objective of this study was to investigate the safety of repeated parenteral ketamine for depression. An electronic survey inquiring about the frequency of adverse events was distributed to providers of parenteral ketamine for depression. In addition, the investigators conducted a search of published studies describing six or more repeated parenteral ketamine treatments administered to individuals for depression, and extracted reported adverse events. The survey was sent to 69 providers, of which 36 responded (52% response rate); after eliminating those that were incomplete, 27 were included in the analysis. The providers in the analysis collectively reported treating 6630 patients with parenteral ketamine for depression, one-third of whom received more than 10 treatments. Only 0.7% of patients experienced an adverse effect that required discontinuation of ketamine. Psychological distress during the treatment was the most frequent cause. Other adverse events were extremely rare (such as bladder dysfunction (0.1%), cognitive decline (0.03%) and psychotic symptoms (0.03%)). Among the 20 published reports of repeated parenteral ketamine treatments, rates of significant adverse events resulting in discontinuation were low (1.2%). The rate of adverse effects reported in the survey and the published literature is low, and suggests that long-term treatment of depression with ketamine is reasonably safe.

Comparable studies

Other cross-sectional and survey studies on ketamine for depression, most cited first.

Study Year Design Participants
Parental Attitudes Toward Use of Ketamine in Adolescent Mood Disorders and Suicidality English-speaking parents of adolescents 2021 Cross-sectional survey n = 283
A Real-World Study on the Use, Effectiveness, and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression: INTEGRATE Study. Adults aged 18-74 years with treatment-resistant depression in Spain 2025 Observational, cross-sectional, retrospective study n = 196
Self-Reported Improvements in Comorbid Post-Traumatic Stress Disorder Symptoms, Depression, Anxiety, and Sleep Among Real-World Patients Receiving Medical Ketamine: Exploring the Role of Adjunct Therapies. Real-world patients with PTSD (n=98) and without PTSD (n=104) who received ketamine... 2025 Secondary analysis of survey data n = 202
Attitudes and Perceptions of Portuguese Psychiatrists and Psychologists on the Clinical Use of Ketamine. Portuguese psychiatrists and psychologists 2025 Cross-sectional survey n = 156
Efficacy of Electroconvulsive Therapy and Ketamine Therapy in Major Depressive Disorder; A Comparative Study Hospitalized patients with major depressive disorder 2023 Comparative cross-sectional study n = 40

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