Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism.
Adult
Antidepressive Agents
/ therapeutic use
Cross-Over Studies
Depressive Disorder, Treatment-Resistant
/ drug therapy
Double-Blind Method
Excitatory Amino Acid Antagonists
/ therapeutic use
Female
Humans
Ketamine
/ metabolism
Male
Middle Aged
Naltrexone
/ pharmacology
Narcotic Antagonists
/ metabolism
Psychiatric Status Rating Scales
Receptors, Opioid
/ metabolism
Suicidal Ideation
Suicide
/ psychology
Treatment Outcome
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
29
12
2018
accepted:
17
05
2019
revised:
30
04
2019
pubmed:
31
8
2019
medline:
26
6
2020
entrez:
31
8
2019
Statut:
ppublish
Résumé
We recently reported that naltrexone blocks antidepressant effects of ketamine in humans, indicating that antidepressant effects of ketamine require opioid receptor activation. However, it is unknown if opioid receptors are also involved in ketamine's antisuicidality effects. Here, in a secondary analysis of our recent clinical trial, we test whether naltrexone attenuates antisuicidality effects of ketamine. Participants were pretreated with naltrexone or placebo prior to intravenous ketamine in a double-blinded crossover design. Suicidality was measured with the Hamilton Depression Rating Scale item 3, Montgomery-Åsberg Depression Rating Scale item 10, and Columbia Suicide Severity Rating Scale. In the 12 participants who completed naltrexone and placebo conditions, naltrexone attenuated the antisuicidality effects of ketamine on all three suicidality scales/subscales (linear mixed model, fixed pretreatment effect, p < 0.01). Results indicate that opioid receptor activation plays a significant role in the antisuicidality effects of ketamine.
Identifiants
pubmed: 31467392
doi: 10.1038/s41380-019-0503-4
pii: 10.1038/s41380-019-0503-4
doi:
Substances chimiques
Antidepressive Agents
0
Excitatory Amino Acid Antagonists
0
Narcotic Antagonists
0
Receptors, Opioid
0
Naltrexone
5S6W795CQM
Ketamine
690G0D6V8H
Types de publication
Clinical Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1779-1786Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : UL1 TR 001085
Pays : International
Références
Stone DM, Simon TR, Fowler KA, Kegler SR, Yuan K, Holland KM, et al. Trends in state suicide rates—United States, 1999–2016 and circumstances contributing to suicide—27 States, 2015. Morb Mortal Wkly Rep. 2018;67:617–24.
doi: 10.15585/mmwr.mm6722a1
Centers for Disease Control and Prevention. Injury prevention & control: data & statistics (WISQARS). 2017. https://www.cdc.gov/injury/wisqars/. Accessed 24 Nov 2018.
Gibbons RD, Hur K, Mann J. Suicide rates and the declining psychiatric hospital bed capacity in the United States. JAMA Psychiatry. 2017;74:849–50.
doi: 10.1001/jamapsychiatry.2017.1227
pubmed: 28614559
pmcid: 28614559
Canuso CM, Singh JB, Fedgchin M, Alphs L, Lane R, Lim P et al. Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. Am J Psychiatry. 2018;175:620–30.
Wilkinson ST, Ballard ED, Bloch MH, Mathew SJ, Murrough JW, Feder A. et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. Am J Psychiatry. 2018;175:150–8.
doi: 10.1176/appi.ajp.2017.17040472
Grunebaum MF, Galfalvy HC, Choo T-H, Keilp JG, Moitra VK, Parris MS et al. Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial. Am J Psychiatry. 2017. 10.1176/appi.ajp.2017.17060647.
Grunebaum MF, Ellis SP, Keilp JG, Moitra VK, Cooper TB, Marver JE, et al. Ketamine versus midazolam in bipolar depression with suicidal thoughts: a pilot midazolam-controlled randomized clinical trial. Bipolar Disord. 2017;19:176–83.
doi: 10.1111/bdi.12487
pubmed: 28452409
pmcid: 28452409
Price RB, Nock MK, Charney DS, Mathew SJ. Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biol Psychiatry. 2009;66:522–6.
doi: 10.1016/j.biopsych.2009.04.029
pubmed: 19545857
pmcid: 19545857
Murrough JW, Soleimani L, DeWilde KE, Collins KA, Lapidus KA, Iacoviello BM, et al. Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial. Psychol Med. 2015;45:3571–80.
doi: 10.1017/S0033291715001506
pubmed: 26266877
pmcid: 26266877
Strasburger SE, Bhimani PM, Kaabe JH, Krysiak JT, Nanchanatt DL, Nguyen TN, et al. What is the mechanism of ketamine’s rapid-onset antidepressant effect? a concise overview of the surprisingly large number of possibilities. J Clin Pharm Ther. 2017;42:147–54.
doi: 10.1111/jcpt.12497
pubmed: 28111761
pmcid: 28111761
Williams NR, Heifets BD, Blasey C, Sudheimer K, Pannu J, Pankow H et al. Attenuation of antidepressant effects of ketamine by opioid receptor antagonism. Am J Psychiatry. 2018;175:1205–15.
Lutz P-E, Mechawar N, Turecki G. Neuropathology of suicide: recent findings and future directions. Mol Psychiatry. 2017;22:1395–412.
doi: 10.1038/mp.2017.141
pubmed: 28696430
pmcid: 28696430
Yovell Y, Bar G, Mashiah M, Baruch Y, Briskman I, Asherov J, et al. Ultra-low-dose buprenorphine as a time-limited treatment for severe suicidal ideation: a randomized controlled trial. Am J Psychiatry. 2016;173:491–8.
doi: 10.1176/appi.ajp.2015.15040535
pubmed: 26684923
pmcid: 26684923
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Am Psychiatr Assoc. 2013. https://doi.org/10.1176/appi.books.9780890425596 .
Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62.
doi: 10.1136/jnnp.23.1.56
pubmed: 14399272
pmcid: 14399272
Sackeim HA. The definition and meaning of treatment-resistant depression. J Clin Psychiatry. 2001;62(Suppl 16):10–17.
pubmed: 11480879
pmcid: 11480879
Abdallah CG, Sanacora G, Duman RS, Krystal JH. The neurobiology of depression, ketamine and rapid-acting antidepressants: is it glutamate inhibition or activation? Pharmacol Ther. 2018;190:148–58.
doi: 10.1016/j.pharmthera.2018.05.010
pubmed: 29803629
pmcid: 29803629
Zarate CA, Singh JB, Quiroz JA, De Jesus G, Denicoff KK, Luckenbaugh DA, et al. A double-blind, placebo-controlled study of memantine in the treatment of major depression. Am J Psychiatry. 2006;163:153–5.
doi: 10.1176/appi.ajp.163.1.153
pubmed: 16390905
pmcid: 16390905
Sleigh J, Harvey M, Voss L, Denny B. Ketamine—more mechanisms of action than just NMDA blockade. Trends Anaesth Crit Care. 2014;4:76–81.
doi: 10.1016/j.tacc.2014.03.002
Stanciu CN, Glass OM, Penders TM. Use of buprenorphine in treatment of refractory depression—a review of current literature. Asian J Psychiatry. 2017;26:94–98.
doi: 10.1016/j.ajp.2017.01.015
Lutz P-E, Kieffer BL. Opioid receptors: distinct roles in mood disorders. Trends Neurosci. 2013;36:195–206.
doi: 10.1016/j.tins.2012.11.002
pubmed: 23219016
pmcid: 23219016
Ahmadi J, Sefidfard Jahromi M. Ultrarapid influence of buprenorphine on major dDepression in opioid-dependent patients: a double blind, randomized clinical trial. Subst Use Misuse. 2018;53:286–9.
doi: 10.1080/10826084.2017.1400063
pubmed: 29148881
pmcid: 29148881
Ionescu DF, Swee MB, Pavone KJ, Taylor N, Akeju O, Baer L, et al. Rapid and sustained reductions in current suicidal ideation following repeated doses of intravenous ketamine: secondary analysis of an open-label study. J Clin Psychiatry. 2016;77:e719–725.
doi: 10.4088/JCP.15m10056
pubmed: 27232360
pmcid: 27232360
Oquendo MA, Volkow ND. Suicide: a silent contributor to opioid-overdose deaths. N Engl J Med. 2018;378:1567–9.
doi: 10.1056/NEJMp1801417
pubmed: 29694805
pmcid: 29694805
Fornili K. The opioid crisis, suicides, and related conditions: multiple clustered syndemics, not singular epidemics. J Addict Nurs. 2018;29:214–20.
doi: 10.1097/JAN.0000000000000240
pubmed: 30180010
pmcid: 30180010
Ducasse D, Holden RR, Boyer L, Artéro S, Calati R, Guillaume S et al. Psychological pain in suicidality: a meta-analysis. J Clin Psychiatry. 2018;79:44–51.
Conejero I, Olié E, Calati R, Ducasse D, Courtet P. Psychological pain, depression, and suicide: recent evidences and future directions. Curr Psychiatry Rep. 2018;20:1–9.
Calati R, Olié E, Ritchie K, Artero S, Courtet P. Suicidal ideation and suicide attempts in the elderly associated with opioid use and pain sensitivity. Psychother Psychosom. 2017;86:373–5.
doi: 10.1159/000478021
pubmed: 29131065
pmcid: 29131065
Olié E, Courtet P, Poulain V, Guillaume S, Ritchie K, Artero S. History of suicidal behaviour and analgesic use in community-dwelling elderly. Psychother Psychosom. 2013;82:341–3.
doi: 10.1159/000350504
pubmed: 23942382
pmcid: 23942382
Garland EL, Riquino MR, Priddy SE, Bryan CJ. Suicidal ideation is associated with individual differences in prescription opioid craving and cue-reactivity among chronic pain patients. J Addict Dis. 2017;36:23–29.
doi: 10.1080/10550887.2016.1220800
pubmed: 27644963
pmcid: 27644963
Riquino MR, Priddy SE, Howard MO, Garland EL. Emotion dysregulation as a transdiagnostic mechanism of opioid misuse and suicidality among chronic pain patients. Borderline Personal Disord Emot Dysregulation. 2018;5:1–9.
Taylor JJ, Borckardt JJ, George MS. Endogenous opioids mediate left dorsolateral prefrontal cortex rTMS-induced analgesia. Pain. 2012;153:1219–25.
doi: 10.1016/j.pain.2012.02.030
pubmed: 22444187
pmcid: 22444187
Taylor JJ, Borckardt JJ, Canterberry M, Li X, Hanlon CA, Brown TR, et al. Naloxone-reversible modulation of pain circuitry by left prefrontal rTMS. Neuropsychopharmacology. 2013;38:1189–97.
doi: 10.1038/npp.2013.13
pubmed: 23314221
pmcid: 23314221
George MS, Raman R, Benedek DM, Pelic CG, Grammer GG, Stokes KT, et al. A two-site pilot randomized 3 day trial of high dose left prefrontal repetitive transcranial magnetic stimulation (rTMS) for suicidal inpatients. Brain Stimul. 2014;7:421–31.
doi: 10.1016/j.brs.2014.03.006
Weissman CR, Blumberger DM, Brown PE, Isserles M, Rajji TK, Downar J, et al. Bilateral repetitive transcranial magnetic stimulation decreases suicidal ideation in depression. J Clin Psychiatry. 2018;79:e11692.
doi: 10.4088/JCP.17m11692
Qin BY, Dai LL, Zheng Y. Efficacy of repetitive transcranial magnetic stimulation for alleviating clinical symptoms and suicidal ideation in elderly depressive patients: a randomized controlled trial. Nan Fang Yi Ke Da Xue Xue Bao. 2017;37:97–101.
pubmed: 28109107
pmcid: 28109107
Scherrer JF, Salas J, Sullivan MD, Ahmedani BK, Copeland LA, Bucholz KK. et al. Impact of adherence to antidepressants on long-term prescription opioid use cessation. Br J Psychiatry. 2018;212:103–11.
doi: 10.1192/bjp.2017.25
pubmed: 29436331
pmcid: 29436331
Lutz P-E, Courtet P, Calati R. The opioid system and the social brain: implications for depression and suicide. J Neurosci Res. 2018;1–13. https://doi.org/10.1002/jnr.24269 [Epub ahead of print].
Lee JD, Nunes EV, Novo P, Bachrach K, Bailey GL, Bhatt S, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet. 2018;391:309–18.
doi: 10.1016/S0140-6736(17)32812-X
pubmed: 29150198
pmcid: 29150198
Schepis TS, Simoni-Wastila L, McCabe SE. Prescription opioid and benzodiazepine misuse is associated with suicidal ideation in older adults. Int J Geriatr Psychiatry. 2019;34:122–9. https://doi.org/10.1002/gps.4999 .
Kuramoto SJ, Chilcoat HD, Ko J, Martins SS. Suicidal ideation and suicide attempt across stages of nonmedical prescription opioid use and presence of prescription opioid disorders among US adults. J Stud Alcohol Drugs. 2012;73:178–84.
doi: 10.15288/jsad.2012.73.178
pubmed: 22333325
pmcid: 22333325
Ashrafioun L, Bishop TM, Conner KR, Pigeon WR. Frequency of prescription opioid misuse and suicidal ideation, planning, and attempts. J Psychiatr Res. 2017;92:1–7.
doi: 10.1016/j.jpsychires.2017.03.011
pubmed: 28364579
pmcid: 28364579
Ilgen MA, Bohnert ASB, Ganoczy D, Bair MJ, Mccarthy JF, Blow FC. Opioid dose and risk of suicide. Pain. 2016;157:1079–84.
doi: 10.1097/j.pain.0000000000000484
pubmed: 26761386
pmcid: 26761386
Semenkovich K, Chockalingam R, Scherrer JF, Panagopoulos VN, Lustman PJ, Ray JM, et al. Prescription opioid analgesics increase risk of major depression: new evidence, plausible neurobiological mechanisms and management to achieve depression prophylaxis. Mo Med. 2014;111:148–54.
pubmed: 30323529
pmcid: 30323529
Salas J, Scherrer JF, Schneider FD, Sullivan MD, Bucholz KK, Burroughs T, et al. New-onset depression following stable, slow, and rapid rate of prescription opioid dose escalation. PAIN. 2017;158:306.
doi: 10.1097/j.pain.0000000000000763
pubmed: 28092649
pmcid: 28092649
Salas J, Scherrer JF, Ahmedani BK, Copeland LA, Bucholz KK, Sullivan MD, et al. Gender and the association between long-term prescription opioid use and new-onset depression. J Pain. 2018;19:88–98.
doi: 10.1016/j.jpain.2017.09.004
pubmed: 29030323
pmcid: 29030323
Scherrer JF, Salas J, Copeland LA, Stock EM, Schneider FD, Sullivan M, et al. Increased risk of depression recurrence after initiation of prescription opioids in noncancer pain patients. J Pain. 2016;17:473–82.
doi: 10.1016/j.jpain.2015.12.012
pubmed: 26884282
pmcid: 26884282
Scherrer JF, Salas J, Sullivan MD, Schneider FD, Bucholz KK, Burroughs T, et al. The influence of prescription opioid use duration and dose on development of treatment resistant depression. Prev Med. 2016;91:110–6.
doi: 10.1016/j.ypmed.2016.08.003
pubmed: 27497660
pmcid: 27497660
Yoon G, Petrakis IL, Krystal JH. Association of combined naltrexone and ketamine with depressive symptoms in a case series of patients with depression and alcohol use disorder. JAMA Psychiatry. 2019;76:337–8. https://doi.org/10.1001/jamapsychiatry.2018.3990 .
Marton T, Barnes DE, Wallace A, Woolley JD. Concurrent use of buprenorphine, methadone, or naltrexone does not inhibit ketamine’s antidepressant activity. Biol Psychiatry. 2019;85:e75–6. https://doi.org/10.1016/j.biopsych.2019.02.008 .
Heifets BD, Williams NR, Bentzley BS, Schatzberg AF. Rigorous trial design is essential to understand the role of opioid receptors in ketamine’s antidepressant effect. JAMA Psychiatry. 2019;76:657–8. https://doi.org/10.1001/jamapsychiatry.2019.0766 .
Barr CS, Schwandt ML, Lindell SG, Higley JD, Maestripieri D, Goldman D, et al. Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates. Proc Natl Acad Sci USA. 2008;105:5277–81.
doi: 10.1073/pnas.0710225105
pubmed: 18378897
pmcid: 18378897
Copeland WE, Sun H, Costello EJ, Angold A, Heilig MA, Barr CS. Child μ-opioid receptor gene variant influences parent–child relations. Neuropsychopharmacology. 2011;36:1165–70.
doi: 10.1038/npp.2010.251
pubmed: 21326192
pmcid: 21326192
Briand LA, Hilario M, Dow HC, Brodkin ES, Blendy JA, Berton O. Mouse model of OPRM1 (A118G) polymorphism increases sociability and dominance and confers resilience to social defeat. J Neurosci. 2015;35:3582–90.
doi: 10.1523/JNEUROSCI.4685-14.2015
pubmed: 25716856
pmcid: 25716856
Carlezon WA, Krystal AD. Kappa-opioid antagonists for psychiatric disorders: from bench to clinical trials. Depress Anxiety. 2016;33:895–906.
doi: 10.1002/da.22500
pubmed: 27699938
pmcid: 27699938
Browne CA, Falcon E, Robinson SA, Berton O, Lucki I. Reversal of stress-induced social interaction deficits by buprenorphine. Int J Neuropsychopharmacol. 2018;21:164–74.
doi: 10.1093/ijnp/pyx079
pubmed: 29020387
pmcid: 29020387
Falcon E, Browne CA, Leon RM, Fleites VC, Sweeney R, Kirby LG, et al. Antidepressant-like effects of buprenorphine are mediated by kappa opioid receptors. Neuropsychopharmacology. 2016;41:2344–51.
doi: 10.1038/npp.2016.38
pubmed: 26979295
pmcid: 26979295
Malcolm R, O’Neil PM, Von JM, Dickerson PC. Naltrexone and dysphoria: a double-blind placebo controlled trial. Biol Psychiatry. 1987;22:710–6.
doi: 10.1016/0006-3223(87)90202-2
pubmed: 3593812
pmcid: 3593812
Miotto K, McCann M, Basch J, Rawson R, Ling W. Naltrexone and dysphoria: fact or myth? Am J Addict. 2002;11:151–60.
doi: 10.1080/10550490290087929
pubmed: 12028745
pmcid: 12028745
Dean AJ, Saunders JB, Jones RT, Young RM, Connor JP, Lawford BR. Does naltrexone treatment lead to depression? Findings from a randomized controlled trial in subjects with opioid dependence. J Psychiatry Neurosci. 2006;31:38–45.
pubmed: 16496034
pmcid: 16496034
Carroll KM, Nich C, Frankforter TL, Yip SW, Kiluk BD, DeVito EE, et al. Accounting for the uncounted: physical and affective distress in individuals dropping out of oral naltrexone treatment for opioid use disorder. Drug Alcohol Depend. 2018;192:264–70.
doi: 10.1016/j.drugalcdep.2018.08.019
pubmed: 30300800
pmcid: 30300800
Kelty E, Hulse G. Fatal and non-fatal opioid overdose in opioid dependent patients treated with methadone, buprenorphine or implant naltrexone. Int J Drug Policy. 2017;46:54–60.
doi: 10.1016/j.drugpo.2017.05.039
pubmed: 28609749
pmcid: 28609749
Kelty E, Hulse G. Examination of mortality rates in a retrospective cohort of patients treated with oral or implant naltrexone for problematic opiate use. Addiction. 2012;107:1817–24.
doi: 10.1111/j.1360-0443.2012.03910.x
pubmed: 22487087
pmcid: 22487087
Mischoulon D, Hylek L, Yeung AS, Clain AJ, Baer L, Cusin C, et al. Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants. J Affect Disord. 2017;208:6–14.
doi: 10.1016/j.jad.2016.08.029
pubmed: 27736689
pmcid: 27736689
Murphy BL, Ravichandran C, Babb SM, Cohen BM. Naltrexone in bipolar disorder with depression: a double-blind, placebo-controlled study. J Clin Psychopharmacol. 2014;34:749–51.
doi: 10.1097/JCP.0000000000000222
pubmed: 25310199
pmcid: 25310199
Pettinati HM, Oslin DW, Kampman KM, Dundon WD, Xie H, Gallis TL, et al. A double-blind, placebo-controlled trial combining sertraline and naltrexone for treating co-occurring depression and alcohol dependence. Am J Psychiatry. 2010;167:668–75.
doi: 10.1176/appi.ajp.2009.08060852
pubmed: 20231324
pmcid: 20231324