Add-on Intravenous Racemic Ketamine May be Best for Treatment-Resistant Depression
Augmentative treatment with intravenous racemic ketamine in adults with treatment-resistant unipolar depression appears to be better than augmentative intranasal esketamine or aripiprazole, suggests a systematic review and network meta-analysis published in the Journal of Affective Disorders.
“Whether intravenous racemic ketamine or lithium is superior is unclear currently,” wrote corresponding author Itsuki Terao, MD, PhD, of Ikokoro Clinic Nihonbashi, Tokyo, Japan, and study coauthors.
To compare the efficacy, tolerability, and acceptability of intravenous racemic ketamine with intranasal esketamine, as well as with the more conventional pharmacologic interventions aripiprazole and lithium, researchers conducted a systematic review and network meta-analysis of 22 randomized controlled trials of augmentation therapy in patients with treatment-resistant unipolar depression.
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All 4 drugs were significantly more effective than placebo, according to the study. However, intravenous racemic ketamine was significantly more effective and acceptable than intranasal esketamine and aripiprazole.
Regarding tolerability, intravenous racemic ketamine did not differ significantly from placebo. Intranasal esketamine and aripiprazole, on the other hand, were significantly less tolerable than placebo, researchers reported.
Meanwhile, lithium was comparable to intravenous racemic ketamine in terms of efficacy, tolerability, and acceptability, analyses showed.
Limitations of the study included the small sample of patients treated with intravenous racemic ketamine and ambiguity regarding adverse effects commonly associated with ketamine, such as dissociation, nausea, increased blood pressure, and headache, which were not well reported in the trials.
“A larger head-to-head trial of intravenous racemic ketamine versus conventional augmentative treatments for treatment-resistant unipolar depression is needed,” researchers advised.
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