Safety of Repeated Administration of Parenteral Ketamine for Depression

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.

Therapeutic Potentials of Ketamine and Esketamine in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature

“…To summarize, the advantages of using ketamine or esketamine can be recapitulated as the following: (i) no requirement for daily administration, as the molecules are administered for limited periods, thereby increasing a patient's compliance and reducing the stigma of prolonged and daily intake of medications; (ii) the availability of nasal spray formulations that, in the case of esketamine, provide better handling and fewer safety profile issues and side effects; and (iii) in the case of concomitant medications, the possibility to reduce doses, thereby again improving safety profiles and reducing side effects [11,101].…”

“…In addition, increasing evidence now points to its therapeutic efficacy in treatment-resistant depression (TRD), as well as a potential agent for reducing and preventing suicide in depressed patients, as it exerts rapid antidepressant properties as early as several hours after administration. This contrasts with traditional antidepressants (e.g., selective serotonin reuptake inhibitors [SSRIs]), that usually require several weeks for clinical responses [9][10][11][12][13][14][15]. An intranasal formulation of esketamine, currently branded as Spravato ® , was approved by the Food and Drug Administration (FDA) in the United States in March 2019, and by the European Commission in December 2019, for [16,17] the treatment of TRD, defined as the lack of response to two or more adequate trials of antidepressant medications in a current moderate to severe depressive episode [12,17,18].…”

Case Report: Repeated Series of Ketamine Infusions in Patients With Treatment-Resistant Depression: Presentation of Five Cases

“…The antidepressant effect of ketamine persists days or weeks beyond treatment, and the assumption may be that the rapid effect will appear, nevertheless, in subsequent ketamine treatment ( 1 ).…”

Letter to the Editor: Role of ketamine in vaso-occlusive crisis of sickle cell disease

“…[ 2 ] A recently published study also concluded that the incidence of adverse effects was low and ketamine is reasonably safe even in the long-term treatment of patients with depression based on the survey and the published studies. [ 3 ] It is important to note that the survey included specialists of diverse groups and the most common route of administration of ketamine was intravenous in the published reports. [ 3 ] Therefore, I believe that low-dose ketamine infusion is safe if it is used under proper monitoring by trained care providers.…”

“…[ 3 ] It is important to note that the survey included specialists of diverse groups and the most common route of administration of ketamine was intravenous in the published reports. [ 3 ] Therefore, I believe that low-dose ketamine infusion is safe if it is used under proper monitoring by trained care providers. The addition of a benzodiazepine (preferably midazolam) would negate the unwanted, fortunately, transient psychotomimetic effects of ketamine, while anticholinergics (preferably glycopyrrolate) may be administered if excessive secretions are troublesome according to the patient's hemodynamic parameters.…”