This pilot study (n=45) found that oral and IV ketamine was as effective as electroconvulsive therapy (ECT) for depression (MDD) and suicidal ideation, and was rated more positively by participants.
Abstract
“Purpose/Background This study was devised to compare the antidepressant and antisuicidal effects of oral and intramuscular (IM) ketamine versus electroconvulsive therapy (ECT).
Methods/Procedures In our pilot study, 45 patients with major depressive disorder [MDD] (based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria) in the age range of 18 to 70 years who were determined suitable candidates for ECT got randomly divided into 3 equal groups. Each group received one of these treatment modalities: 0.5 mg/kg of IM ketamine; 1 mg/kg of oral ketamine; and ECT in 6 to 9 sessions during 3 weeks. Depression and suicidal ideation scores were recorded using the Hamilton Depression Rating Scale and the Beck Scale for Suicidal Ideation, respectively, at baseline, 24 hours, 1 week, 2 weeks, and 3 weeks within the intervention. The measurements were repeated 1 week and 1 month after the end of the intervention as well. Vital signs and adverse effects were noted. Finally, satisfaction levels of patients for each method were recorded and compared between groups.
Findings/Results The Hamilton Depression Rating Scale and the Beck Scale for Suicidal Ideation scores significantly improved in all groups compared with baseline with no significant differences between the 3 groups. The adverse effects for ketamine-consuming groups such as dissociative symptoms were brief and transient, whereas memory loss for the ECT group remained up to 1 month in some patients. Ketamine-receiving groups preferred it more than ECT.
Implications/Conclusions Oral and IM ketamine probably have equal antidepressant in addition to more antisuicidal effects compared with ECT but had less cognitive adverse effects and higher preference by patients. Thereby, ketamine can be an alternative method in the treatment of patients with severe and/or suicidal MDD.”
Authors: Dorna Kheirabadi, Gholam R. Kheirabadi, Zahra Mirlohi, Mohammad J. Tarrahi & Amir Norbaksh
Summary
This study compared the antidepressant and antisuicidal effects of ketamine and ECT.
MDD is a common psychiatric disorder with 17% prevalence and a significant healthcare cost. Pharmacotherapy and electroconvulsive therapy are the common therapeutic strategies, but antidepressants have a delayed response and ECT has complications.
A clinical trial performed in 2000 revealed that 0.5 mg/kg of ketamine for 40 minutes alleviated depression in 8 MDD patients. Further studies were required to determine the optimal route of administration, and a systematic review concluded that a single infusion of ketamine has a short-term favorable outcome on suicidal thoughts.
Ketamine administered intramuscularly (IM) is also effective as an antidepressant, and the responses are comparable with IV ketamine administration.
Ketamine has shown antidepressant effects in refractory cases of depression. It can be consumed orally by adding flavors and sweeteners to eliminate its bitter taste, but the bioavailability is low compared with IM injection, so higher doses are necessary in oral form.
A systematic review on oral ketamine for depression published in 2019 suggested that it had considerable antidepressant effects.
Most studies focused on IV and oral administration of ketamine. This study compared the antidepressant and antisuicidal effects of oral ketamine with ECT and studied patients’ satisfaction and adverse effects.
MATERIALS AND METHODS
Forty-five patients with MDD and one of the symptoms of suicidal ideation, treatment resistance, severe symptoms, and agitation were randomized to 3 arms (15 patients in each arm) via block randomization method by a nurse who had no further role in the study.
Participants who were inserted in the ECTarm received 6 to 9 sessions of ECT during 3 weeks the same as their routine ECT treatment program in our hospital. Succinylcholine was administered under the supervision of an anesthesiologist and his expert team.
Participants in the IM ketamine arm took 0.5 mg/kg of R-ketamine repeated for 6 to 9 injections in gluteus medius site during 3 weeks with a 2- to 3-day interval.
The third group of participants received 1 mg/kg of oral R-ketamine every 2 to 3 day up to 6 to 9 sessions during 3 weeks, and they were also under the supervision of a psychiatric resident and in the psychiatric emergency department.
Patient’s agreement to engaging in the treatment, preference over other medications used before, motivation to continue treatment, and overall satisfaction with the current method are all measured.
The collected data were analyzed using SPSS 20 and reported as n (%) or means SD. ANOVA, 1-way ANOVA, and Tukey test were used for post hoc analysis.
RESULTS
45 patients diagnosed with MDD were divided into 3 groups. There were no significant differences between the 3 groups regarding age and sex.
Depression and suicide scores were significantly decreased for all 3 intervention groups. Although the intervention P value between groups was not significant, the interaction P value was significant, and the differences between groups at second day and second week during intervention were significant.
Electroconvulsive therapy and ketamine both were tolerated well, but ECT was associated with cognitive and memory impairments that could last up to 1 month.
DISCUSSION
The results show that repeated administration of 0.5 mg/kg of IM ketamine and 1 mg/kg of oral ketamine had antidepressant and antisuicidal effects comparable with ECT during intervention, but the effects did not sustain on follow-ups and duration of antidepressant effect were more favorable for ECT group.
Ketamine, an N-methyl-D-aspartate receptor antagonist, proved its antidepressant qualities in subanesthetic doses since 1990. Its antidepressant and antisuicidal ideation effects were rapid in contrast to the monoamine-based antidepressants.
Studies suggest that repeated doses of ketamine could be a strategy for MDD patients and could lead to prolonged therapeutic outcomes. However, a study on patients with treatment-resistant depression and chronic suicidal ideation found no significant differences between ketamine and placebo.
A placebo-controlled trial showed that 1 mg/kg of oral and 0.5 mg/kg of IM ketamine could create rapid and sustained antidepressant effects and reduce suicidal ideation equal ECT when administered in repeated doses (6 – 9 sessions during 3 weeks).
ECT is an invasive therapeutic method that requires anesthesia induction and constant supervision of an anesthesiologist and an intensive care team. Ketamine may be a valuable antidepressants and antisuicidal treatment with lower risk and better tolerable adverse effects.
Ketamine use may be beneficial for treating depression symptoms and suicidal ideation, but it is not suitable for bipolar, substance dependence, psychotic, or physically ill patients. The potential risk of ketamine abuse remains a concern for psychiatrists prescribing ketamine.
LIMITATIONS
In this study, oral ketamine was compared with intramuscular ketamine, but we did not measure systemic ketamine concentration, and we did not choose a placebo group to compare treatment methods with.