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Propofol for Treatment-Resistant Depression: A Pilot Study.

ABSTRACT: Background:We 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. Methods:Ten 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. Results:Propofol 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. Conclusions:These 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.

SUBMITTER: Mickey BJ

PROVIDER: S-EPMC6276046 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Propofol for Treatment-Resistant Depression: A Pilot Study.

Mickey Brian J BJ White Andrea T AT Arp Anna M AM Leonardi Kolby K Torres Marina M MM Larson Adam L AL Odell David H DH Whittingham Sara A SA Beck Michael M MM Jessop Jacob E JE Sakata Derek J DJ Bushnell Lowry A LA Pierson Matthew D MD Solzbacher Daniela D Kendrick E Jeremy EJ Weeks Howard R HR Light Alan R AR Light Kathleen C KC Tadler Scott C SC

The international journal of neuropsychopharmacology 20181201 12

<h4>Background</h4>We 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.<h4>Methods</h4>Ten participants with moderate-to-severe medication-resistant depression (age 18-45 years and otherwise healthy) each rece ...[more]

PMID: 30260415

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Project description:INTRODUCTION:While the psychiatric benefits of ketamine have been verified through clinical trials, there is limited information about ketamine augmentation in patients with treatment-resistant bipolar depression (TRBPD). Hence, in the present study, we investigate the therapeutic efficacy and functional brain alterations associated with multi-infusion ketamine augmentation in patients with TRBPD. METHODS:The present three-week study included 38 patients with TRBPD, all of whom received a series of nine ketamine injections over the study period. The Hamilton Depression Rating Scale (HAMD) was used to assess the effects of multi-infusion ketamine combined with mood stabilizers. Brain function was evaluated by global functional connectivity density (gFCD). RESULTS:Adjunctive treatment with multiple infusions of ketamine, when combined with a mood stabilizer, could effectively alleviate depressive symptoms for one week, yet the symptoms began to relapse during the second week. Functional brain alterations were detected via gFCD. Specifically, gFCD reductions were mainly found in the bilateral insula, right caudate nucleus, and bilateral inferior frontal gyrus, while increased gFCD was mainly located in the bilateral postcentral gyrus, subgenual anterior cingulate cortex, bilateral thalamus, and cerebellum. Although gFCD alterations were sustained for up to three weeks after the first ketamine infusion, the antidepressant effects of ketamine augmentation sharply declined from the end of the second week of treatment. CONCLUSIONS:Multi-infusion ketamine augmentation can rapidly alleviate depressive symptoms in patients with TRBPD. The clinical effects were primarily visible in the first week after treatment and partially sustained for two weeks; however, the therapeutic effects and related functional brain alterations sharply decreased from the end of the second week. Based on these findings, we demonstrated that the clinical efficacy and functional brain alterations induced by ketamine augmentation are transient.

Project description:BackgroundPeripartum depression is a leading cause of disease burden for women and yet there is little evidence as to how often peripartum depression does not respond to treatment and becomes treatment resistant depression. We sought to determine the incidence of treatment resistant depression (TRD) in women with peripartum depression.MethodsPopulation based retrospective cohort study using a large US claims database. Peripartum depression was defined as having a depression diagnosis during pregnancy or up to 6 months after the end of pregnancy. We included women with prevalent or incident depression. The outcome was the development of TRD within 1 year after the diagnosis of peripartum depression. TRD was defined as having 3 distinct antidepressants or 1 antidepressant and 1 antipsychotic in 1 year. Women with peripartum depression may not be exposed to pharmacological treatments early in pregnancy, therefore we created two groups: 1. women with peripartum depression, and 2. women with peripartum depression diagnosed 3 months before a live birth delivery or within 6 months after that delivery.ResultsThere were 3,207,684 pregnant women, of whom 2.5% had peripartum depression. Of these women half had incident depression during pregnancy. Five percent of women with peripartum depression developed TRD within 1 year of the depression diagnosis. The risk of developing TRD was 50% higher in women with prevalent depression than in women with incident peripartum depression (P < 0.0001). Results were similar in women with peripartum depression diagnosed later in their pregnancy. Women who went on to develop TRD had more substance use disorders, anxiety, insomnia and painful conditions.ConclusionsTRD occurs in approximately 5% of women with peripartum depression. The risk of TRD is higher in pregnant women with a history of depression. Women who went on to develop TRD had more psychiatric comorbidities and painful conditions than women who did not.

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Propofol for Treatment-Resistant Depression: A Pilot Study.

Publications

Propofol for Treatment-Resistant Depression: A Pilot Study.

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