Propofol for Treatment-Resistant Depression: A Pilot Study

Abstract

BackgroundWe hypothesized that propofol, a unique general anesthetic that engages N-methyl-D-aspartate and gamma-aminobutyric acid receptors, has antidepressant properties. This open-label trial was designed to collect preliminary data regarding the feasibility, tolerability, and efficacy of deep propofol anesthesia for treatment-resistant depression.MethodsTen participants with moderate-to-severe medication-resistant depression (age 18–45 years and otherwise healthy) each received a series of 10 propofol infusions. Propofol was dosed to strongly suppress electroencephalographic activity for 15 minutes. The primary depression outcome was the 24-item Hamilton Depression Rating Scale. Self-rated depression scores were compared with a group of 20 patients who received electroconvulsive therapy.ResultsPropofol treatments were well tolerated by all subjects. No serious adverse events occurred. Montreal Cognitive Assessment scores remained stable. Hamilton scores decreased by a mean of 20 points (range 0–45 points), corresponding to a mean 58% improvement from baseline (range 0–100%). Six of the 10 subjects met the criteria for response (>50% improvement). Self-rated depression improved similarly in the propofol group and electroconvulsive therapy group. Five of the 6 propofol responders remained well for at least 3 months. In posthoc analyses, electroencephalographic measures predicted clinical response to propofol.ConclusionsThese findings demonstrate that high-dose propofol treatment is feasible and well tolerated by individuals with treatment-resistant depression who are otherwise healthy. Propofol may trigger rapid, durable antidepressant effects similar to electroconvulsive therapy but with fewer side effects. Controlled studies are warranted to further evaluate propofol’s antidepressant efficacy and mechanisms of action.ClinicalTrials.gov: NCT02935647.

Encoding, Consolidation, and Renormalization in Depression: Synaptic Homeostasis, Plasticity, and Sleep Integrate Rapid Antidepressant Effects

“…We recently reported that nitrous oxide ("laughing gas"), an NMDAR-blocking anesthetic possessing rapid antidepressant potential (Nagele et al, 2015), increases markers of cortical excitation, including the expression of immediate early genes (IEGs) such as c-Fos (Fos protooncogene), Arc, and Homer1 (homer protein homolog 1) (Kohtala et al, 2019b). Whether other anesthetics with antidepressant potential, such as isoflurane (Langer et al, 1995;Weeks et al, 2013;Antila et al, 2017) or propofol (Mickey et al, 2018), also regulate cortical excitation in a similar manner remains to be investigated. Several reports have, however, highlighted the paradoxical excitation that frequently takes place during general anesthesia, characterized by a pattern of burst-suppression in the cortical EEG (Kroeger and Amzica, 2007;Ferron et al, 2009).…”

Sensations of patients and their satisfaction during awake craniotomy

“…Как уже обсуждалось, его уникальные фармакологические свойства позволяют практически управляемо включать и выключать человеческое сознание без какихлибо серьезных постэффектов. Но есть небольшая, не слишком афишируемая информация, что пропофол все же обладает (в особенности если он используется в чистом виде, вне комбинации с другими препаратами) определенным циклотимическим эффектом [47][48][49].…”

Lack of antidepressant effects of burst-suppressing isoflurane anesthesia in adult male Wistar outbred rats subjected to chronic mild stress

“…Weeks et al demonstrated that a series of ten burst-suppressing isoflurane anesthesia sessions for 15 minutes was comparable to ECT in antidepressant efficacy in patients with medication-refractory depression, and more tolerable than ECT regarding neurocognitive side effects [42]. The same group subsequently reported similar findings with repeated propofol anesthesia [43]. Moreover, we and others have shown that a single isoflurane anesthesia exposure produces antidepressant-like effects in the learned helplessness depression model and in the forced swim test [44,45], while halothane, another anesthetic agent that produces negligible burst-suppression, lacks such effects [45].…”