FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2920683752> ?p ?o ?g. }

• W2920683752 endingPage "250" @default.
• W2920683752 startingPage "249" @default.
• W2920683752 abstract "Back to table of contents Previous article Next article Letters to the EditorFull AccessInterpreting Ketamine’s Opioid Receptor Dependent Effect: Response to SanacoraBoris D. Heifets, M.D., Ph.D., Nolan R. Williams, M.D., Christine Blasey, Ph.D., Keith Sudheimer, Ph.D., Carolyn I. Rodriguez, M.D., Ph.D., Alan F. Schatzberg, M.D.Boris D. HeifetsSearch for more papers by this author, M.D., Ph.D., Nolan R. WilliamsSearch for more papers by this author, M.D., Christine BlaseySearch for more papers by this author, Ph.D., Keith SudheimerSearch for more papers by this author, Ph.D., Carolyn I. RodriguezSearch for more papers by this author, M.D., Ph.D., Alan F. SchatzbergSearch for more papers by this author, M.D.Published Online:1 Mar 2019https://doi.org/10.1176/appi.ajp.2018.18091061rAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We thank Dr. Sanacora for his thoughtful comments on our recent article (1), in which we reported that pretreatment with naltrexone, an opioid receptor antagonist, markedly attenuated the rapid antidepressant response to ketamine in patients with treatment-resistant depression. His letter raises an important alternative interpretation of the study’s findings; namely, that the results may reflect the need for a normally functioning endogenous opioid system to express an antidepressant response to ketamine. This possibility has two implications: first, ketamine’s antidepressant mechanism may require endogenous opioid release; second, perhaps the endogenous opioid system is a final common pathway for many antidepressant effects, including placebo.Our study was a first attempt at exploring the pharmacological mechanism of ketamine’s antidepressant effect in humans. We broadly agree with Dr. Sanacora that an opioid receptor antagonist’s effect can be explained either by direct interaction at the opioid receptor, an indirect interaction at the cellular level, perhaps mediated by cross-talk between N-methyl-d-aspartate and opioid receptors, or by an indirect effect wherein the action of endogenous opioids, presumably stimulated by ketamine infusion, is blocked. As we stated in our article, “opioid receptors are necessary for ketamine’s acute antidepressant effect” (1, p. 1210), and “ketamine produces its acute antidepressant response primarily through direct and/or indirect actions at the mu opioid receptors” (1, p. 1210). Our results cannot distinguish between a direct or indirect mechanism of ketamine on the opioid system. The available preclinical evidence, cited in our article, shows that ketamine can bind opioid receptors, which would be the simplest interpretation of the study’s findings. We acknowledged other potential mechanisms in our article, and we agree that endogenous opioid release may play an important role in ketamine’s antidepressant response.Could endogenous opioid mechanisms explain antidepressant responses to many active agents, including ketamine, as well as to placebo? We cannot discount this possibility. However, we know of no other evidence that naltrexone blocks or reverses antidepressant responses or the efficacy of antidepressants in other conditions, such as appetitive behaviors. To the contrary, sertraline in combination with naltrexone produces greater antidepressant effects in depressed alcoholic patients than does naltrexone alone, sertraline alone, or placebo alone (2). In that study, placebo response was similar in the sertraline and naltrexone groups. In another trial of bupropion plus naltrexone compared with placebo for weight loss (3), the effect in the bupropion/naltrexone–treated group on weight loss was significantly greater than that seen with placebo, and the bupropion/naltrexone subjects did not show greater rates of depression. Similarly, in another study, bupropion/naltrexone was significantly more effective than bupropion/placebo for smoking cessation (4). Thus, it seems unlikely that naltrexone generally blocks the effect of antidepressant treatments, whether in trials measuring efficacy for depression, or for other symptoms or behaviors, including those associated with dysregulated appetitive behaviors.We support Dr. Sanacora’s comment on being careful not to overinterpret the mechanistic implications of our findings. At the same time, we remain steadfast in our conclusion that caution against widespread and repeated use of ketamine is warranted. The epidemiological evidence speaks for itself; ketamine can be highly reinforcing, lends itself to abuse, and may result in significant adverse medical and behavioral sequelae. We believe that our findings suggest an explanation for ketamine’s abuse potential and bring attention to this aspect of ketamine’s use as an antidepressant treatment that has, so far, been underappreciated in the psychiatric literature. We support Dr. Sanacora’s suggestion of a registry for outpatient ketamine administration.Department of Psychiatry and Behavioral Sciences (Williams, Blasey, Sudheimer, Rodriguez, Schatzberg) and Department of Anesthesiology, Perioperative, and Pain Medicine (Heifets), Stanford University, Stanford, Calif.Send correspondence to Dr. Heifets ([email protected]) or Dr. Williams ([email protected]).Drs. Heifets and Williams share first authorship.The authors’ disclosures accompany the original article.References1 Williams NR, Heifets BD, Blasey C, et al.: Attenuation of antidepressant effects of ketamine by opioid receptor antagonism. Am J Psychiatry 2018; 175:1205–1215Link, Google Scholar2 Pettinati HM, Oslin DW, Kampman KM, et al.: A double-blind, placebo-controlled trial combining sertraline and naltrexone for treating co-occurring depression and alcohol dependence. Am J Psychiatry 2010; 167:668–675Link, Google Scholar3 Greenway FL, Fujioka K, Plodkowski RA, et al.: Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2010; 376:595–605Crossref, Medline, Google Scholar4 Mooney ME, Schmitz JM, Allen S, et al.: Bupropion and naltrexone for smoking cessation: a double-blind randomized placebo-controlled clinical trial. Clin Pharmacol Ther 2016; 100:344–352Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byMechanisms of ketamine and its metabolites as antidepressantsBiochemical Pharmacology, Vol. 197New Medications for Neuropsychiatric DisordersPsychiatric Clinics of North America, Vol. 43, No. 2Psychiatry and Clinical Neurosciences, Vol. 73, No. 10 Volume 176Issue 3 March 01, 2019Pages 249-250 Metrics KeywordsKetamineOpioidNaltrexoneDepressionPDF download History Accepted 15 October 2018 Published online 1 March 2019 Published in print 1 March 2019" @default.
• W2920683752 created "2019-03-11" @default.
• W2920683752 creator A5019084880 @default.
• W2920683752 creator A5025170450 @default.
• W2920683752 creator A5031527996 @default.
• W2920683752 creator A5056450962 @default.
• W2920683752 creator A5070799330 @default.
• W2920683752 creator A5074022923 @default.
• W2920683752 date "2019-03-01" @default.
• W2920683752 modified "2023-10-14" @default.
• W2920683752 title "Interpreting Ketamine’s Opioid Receptor Dependent Effect: Response to Sanacora" @default.
• W2920683752 doi "https://doi.org/10.1176/appi.ajp.2018.18091061r" @default.
• W2920683752 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30818991" @default.
• W2920683752 hasPublicationYear "2019" @default.
• W2920683752 type Work @default.
• W2920683752 sameAs 2920683752 @default.
• W2920683752 citedByCount "3" @default.
• W2920683752 countsByYear W29206837522019 @default.
• W2920683752 countsByYear W29206837522020 @default.
• W2920683752 countsByYear W29206837522022 @default.
• W2920683752 crossrefType "journal-article" @default.
• W2920683752 hasAuthorship W2920683752A5019084880 @default.
• W2920683752 hasAuthorship W2920683752A5025170450 @default.
• W2920683752 hasAuthorship W2920683752A5031527996 @default.
• W2920683752 hasAuthorship W2920683752A5056450962 @default.
• W2920683752 hasAuthorship W2920683752A5070799330 @default.
• W2920683752 hasAuthorship W2920683752A5074022923 @default.
• W2920683752 hasBestOaLocation W29206837521 @default.
• W2920683752 hasConcept C11171543 @default.
• W2920683752 hasConcept C118552586 @default.
• W2920683752 hasConcept C126322002 @default.
• W2920683752 hasConcept C142724271 @default.
• W2920683752 hasConcept C15744967 @default.
• W2920683752 hasConcept C170493617 @default.
• W2920683752 hasConcept C204787440 @default.
• W2920683752 hasConcept C27081682 @default.
• W2920683752 hasConcept C2776885963 @default.
• W2920683752 hasConcept C2777972943 @default.
• W2920683752 hasConcept C2779177272 @default.
• W2920683752 hasConcept C2779886867 @default.
• W2920683752 hasConcept C2780795376 @default.
• W2920683752 hasConcept C2781063702 @default.
• W2920683752 hasConcept C3017995582 @default.
• W2920683752 hasConcept C558461103 @default.
• W2920683752 hasConcept C71924100 @default.
• W2920683752 hasConcept C98274493 @default.
• W2920683752 hasConceptScore W2920683752C11171543 @default.
• W2920683752 hasConceptScore W2920683752C118552586 @default.
• W2920683752 hasConceptScore W2920683752C126322002 @default.
• W2920683752 hasConceptScore W2920683752C142724271 @default.
• W2920683752 hasConceptScore W2920683752C15744967 @default.
• W2920683752 hasConceptScore W2920683752C170493617 @default.
• W2920683752 hasConceptScore W2920683752C204787440 @default.
• W2920683752 hasConceptScore W2920683752C27081682 @default.
• W2920683752 hasConceptScore W2920683752C2776885963 @default.
• W2920683752 hasConceptScore W2920683752C2777972943 @default.
• W2920683752 hasConceptScore W2920683752C2779177272 @default.
• W2920683752 hasConceptScore W2920683752C2779886867 @default.
• W2920683752 hasConceptScore W2920683752C2780795376 @default.
• W2920683752 hasConceptScore W2920683752C2781063702 @default.
• W2920683752 hasConceptScore W2920683752C3017995582 @default.
• W2920683752 hasConceptScore W2920683752C558461103 @default.
• W2920683752 hasConceptScore W2920683752C71924100 @default.
• W2920683752 hasConceptScore W2920683752C98274493 @default.
• W2920683752 hasIssue "3" @default.
• W2920683752 hasLocation W29206837521 @default.
• W2920683752 hasLocation W29206837522 @default.
• W2920683752 hasOpenAccess W2920683752 @default.
• W2920683752 hasPrimaryLocation W29206837521 @default.
• W2920683752 hasRelatedWork W1577133669 @default.
• W2920683752 hasRelatedWork W1979335616 @default.
• W2920683752 hasRelatedWork W1979368316 @default.
• W2920683752 hasRelatedWork W2010220841 @default.
• W2920683752 hasRelatedWork W2011015534 @default.
• W2920683752 hasRelatedWork W2027069237 @default.
• W2920683752 hasRelatedWork W2089497531 @default.
• W2920683752 hasRelatedWork W2215974254 @default.
• W2920683752 hasRelatedWork W4224243283 @default.
• W2920683752 hasRelatedWork W4319600105 @default.
• W2920683752 hasVolume "176" @default.
• W2920683752 isParatext "false" @default.
• W2920683752 isRetracted "false" @default.
• W2920683752 magId "2920683752" @default.
• W2920683752 workType "article" @default.