Abstract
Anhedonia is a common, persistent, and disabling condition. However, available therapeutics primarily focus on the reduction of depressive and negative symptoms rather than amelioration of deficits in positive affect. As such, extant drug treatments remain largely ineffective in treating symptoms of anhedonia. Ketamine is a rapid-acting and novel therapeutic treatment for treatment-resistant depression, which has also been demonstrated to attenuate symptoms of anhedonia. However, the literature on the anti-anhedonic effects of ketamine is limited—especially within independent dimensions of this symptom domain. Herein, this review examined the impact of ketamine treatment on anhedonia and its dimensions on anticipatory, consummatory, and motivation-related reward deficits. Overall, the findings have shown a trend towards symptom reduction and/or improvements in anhedonia and their respective subdomains, in both human and preclinical studies, as well as its potential to provide additional benefit in reducing suicidality and improving quality-of-life. Although further research is required in understanding the long-term efficacy and mechanism, ketamine may provide an effective and rapid-acting therapeutic in an otherwise unmet domain.
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Abdallah CG, De Feyter HM, Averill LA, Jiang L, Averill CL, Chowdhury GMI, Purohit P, de Graaf RA, Esterlis I, Juchem C, Pittman BP, Krystal JH, Rothman DL, Sanacora G, Mason GF (2018) The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects. Neuropsychopharmacology 43(10):2154. https://doi.org/10.1038/S41386-018-0136-3
Ago Y, Hasebe S, Nishiyama S, Oka S, Onaka Y, Hashimoto H, Takuma K, & Matsuda T (2015) The female encounter test: a novel method for evaluating reward-seeking behavior or motivation in mice. Int J Neuropsychopharmacol 18(11). https://doi.org/10.1093/ijnp/pyv062
Amonoo HL, Fenech A, Greer JA, Temel JS, Huffman JC, El-Jawahri A (2020) Does desire to pursue pleasurable activities matter? The impact of pretransplantation anhedonia on quality of life and fatigue in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 26(8):1477–1481. https://doi.org/10.1016/j.bbmt.2020.04.014
Aricioğlu F, Yalcinkaya C, Ozkartal CS, Tuzun E, Sirvanci S, Kucukali CI, Utkan T (2020) NLRP1-mediated antidepressant effect of ketamine in chronic unpredictable mild stress model in rats. Psychiatry Investigation 17(4), 283–291. https://doi.org/10.30773/pi.2019.0189
Bahji A, Vazquez GH, & Zarate CA (2021) Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis. In Journal of Affective Disorders (278 542–555). Elsevier B.V. https://doi.org/10.1016/j.jad.2020.09.071
Ballard ED, Wills K, Lally N, Richards EM, Luckenbaugh DA, Walls T, Ameli R, Niciu MJ, Brutsche NE, Park L, Zarate CA (2017) Anhedonia as a clinical correlate of suicidal thoughts in clinical ketamine trials. J Affect Disord 218:195–200. https://doi.org/10.1016/j.jad.2017.04.057
Barthel AL, Pinaire MA, Curtiss JE, Baker AW, Brown ML, Hoeppner SS, Bui E, Simon NM, Hofmann SG (2020) Anhedonia is central for the association between quality of life, metacognition, sleep, and affective symptoms in generalized anxiety disorder: a complex network analysis. J Affect Disord 277:1013–1021. https://doi.org/10.1016/j.jad.2020.08.077
Belujon P, Grace AA (2017) Dopamine system dysregulation in major depressive disorders. Int J Neuropsychopharmacol 20(12):1036–1046. https://doi.org/10.1093/IJNP/PYX056
Berridge KC, Kringelbach ML (2011) Building a neuroscience of pleasure and well-being. Psychology of Well-Being: Theory, Research and Practice 1(1):3. https://doi.org/10.1186/2211-1522-1-3
Bonanni L, Gualtieri F, Lester D, Falcone G, Nardella A, Fiorillo A, & Pompili M (2019) Can anhedonia be considered a suicide risk factor? A review of the literature. In Medicina (Lithuania) (55 Issue 8). MDPI AG. https://doi.org/10.3390/medicina55080458
Cao B, Park C, Subramaniapillai M, Lee Y, Iacobucci M, Mansur RB, Zuckerman H, Phan L, & McIntyre RS (2019a) The efficacy of vortioxetine on anhedonia in patients with major depressive disorder. Front Psychiatry 10(JAN) 17. https://doi.org/10.3389/fpsyt.2019.00017
Cao B, Zhu J, Zuckerman H, Rosenblat JD, Brietzke E, Pan Z, Subramanieapillai M, Park C, Lee Y, & McIntyre RS (2019b) Pharmacological interventions targeting anhedonia in patients with major depressive disorder: a systematic review. In Progress in Neuro-Psychopharmacology and Biological Psychiatry (92 109–117). Elsevier Inc. https://doi.org/10.1016/j.pnpbp.2019.01.002
Cooper JA, Arulpragasam AR, & Treadway MT (2018) Anhedonia in depression: biological mechanisms and computational models. In Current Opinion in Behavioral Sciences (22 128–135). Elsevier Ltd. https://doi.org/10.1016/j.cobeha.2018.01.024
Craske MG, Meuret AE, Ritz T, Treanor M, Dour HJ (2016) Treatment for anhedonia: a neuroscience driven approach. Depress Anxiety 33(10):927–938. https://doi.org/10.1002/da.22490
Delfino RS, Del-Porto JA, Surjan J, Magalhães E, Del Sant LC, Lucchese AC, Tuena MA, Nakahira C, Fava VAR, Steglich MS, Barbosa MG, Sarin LM, Lacerda ALT (2021) Comparative effectiveness of esketamine in the treatment of anhedonia in bipolar and unipolar depression. J Affect Disord 278:515–518. https://doi.org/10.1016/j.jad.2020.09.056
Der-Avakian A, Markou A (2012) The neurobiology of anhedonia and other reward-related deficits. In Trends in Neurosciences. https://doi.org/10.1016/j.tins.2011.11.005
Destoop M, Morrens M, Coppens V, & Dom G (2019) Addiction, anhedonia, and comorbid mood disorder. A narrative review. In Frontiers in Psychiatry (10, Issue MAY). Frontiers Media S.A. https://doi.org/10.3389/fpsyt.2019.00311
Dichter GS (2010) Anhedonia in unipolar major depressive disorder: a review. In The Open Psychiatry Journal (4)
Dimick MK, Hird MA, Fiksenbaum LM, Mitchell RHB, Goldstein BI (2021) Severe anhedonia among adolescents with bipolar disorder is common and associated with increased psychiatric symptom burden. J Psychiatr Res 134:200–207. https://doi.org/10.1016/j.jpsychires.2020.12.031
Donahue RJ, Muschamp JW, Russo SJ, Nestler EJ, Carlezon WA (2014) Effects of striatal ΔFosB over expression and ketamine on social defeat stress-induced anhedonia in mice. Biol Psychiat 76(7):550–558. https://doi.org/10.1016/j.biopsych.2013.12.014
Ducasse D, Dubois J, Jaussent I, Azorin JM, Etain B, Gard S, Henry C, Bougerol T, Kahn JP, Aubin V, Bellivier F, Belzeaux R, Dubertret C, Dubreucq J, Llorca PM, Loftus J, Passerieux C, Polosan M, Samalin L, … Courtet P (2021) Association between anhedonia and suicidal events in patients with mood disorders: a 3-year prospective study. Depression and Anxiety, 38(1), 17–27. https://doi.org/10.1002/da.23072
Ducasse D, Loas G, Dassa D, Gramaglia C, Zeppegno P, Guillaume S, Olié E, Courtet P (2018) Anhedonia is associated with suicidal ideation independently of depression: a meta-analysis. Depress Anxiety 35(5):382–392. https://doi.org/10.1002/da.22709
Dutheil S, Ota KT, Wohleb ES, Rasmussen K, Duman RS (2016) High-fat diet induced anxiety and anhedonia: impact on brain homeostasis and inflammation. Neuropsychopharmacol 41(7):1874–1887. https://doi.org/10.1038/npp.2015.357
Fang X, Zhan G, Zhang J, Xu H, Zhu B, Hu Y, Yang C, Luo A (2019) Abnormalities in inflammatory cytokines confer susceptible to chronic neuropathic pain-related anhedonia in a rat model of spared nerve injury. Clin Psychopharmacol Neurosci 17(2):189–199. https://doi.org/10.9758/cpn.2019.17.2.189
Garcia LSB, Comim CM, Valvassori SS, Réus GZ, Stertz L, Kapczinski F, Gavioli EC, Quevedo J (2009) Ketamine treatment reverses behavioral and physiological alterations induced by chronic mild stress in rats. Prog Neuropsychopharmacol Biol Psychiatry 33(3):450–455. https://doi.org/10.1016/j.pnpbp.2009.01.004
Gard DE, Kring AM, Gard MG, Horan WP, Green MF (2007) Anhedonia in schizophrenia: distinctions between anticipatory and consummatory pleasure. Schizophr Res. https://doi.org/10.1016/j.schres.2007.03.008
Gorwood P (2008) Neurobiological mechanisms of anhedonia. Dialogues in Clinical Neuroscience, 10(3), 291–299. https://doi.org/10.31887/dcns.2008.10.3/pgorwood
Haroon E, Chen X, Li Z, Patel T, Woolwine BJ, Hu XP, Felger JC, & Miller AH (2018) Increased inflammation and brain glutamate define a subtype of depression with decreased regional homogeneity, impaired network integrity, and anhedonia. Translational Psychiatry, 8(1). https://doi.org/10.1038/S41398-018-0241-4
Ho N, Sommers M (2013) Anhedonia: a concept analysis. In Archives of Psychiatric Nursing. https://doi.org/10.1016/j.apnu.2013.02.001
Höflich A, Michenthaler P, Kasper S, Lanzenberger R (2018) Circuit mechanisms of reward, anhedonia, and depression. In International Journal of Neuropsychopharmacology. https://doi.org/10.1093/ijnp/pyy081
John CS, Smith KL, Van’T Veer A, Gompf HS, Carlezon WA, Cohen BM, Ngür D, Bechtholt-Gompf AJ (2012) Blockade of astrocytic glutamate uptake in the prefrontal cortex induces anhedonia. Neuropsychopharmacology 37(11):2467. https://doi.org/10.1038/NPP.2012.105
Kadriu B, Musazzi L, Henter ID, Graves M, Popoli M, & Zarate CA (2019) Glutamatergic neurotransmission: pathway to developing novel rapid-acting antidepressant treatments. In International Journal of Neuropsychopharmacology (22, Issue 2, 119–135). Oxford University Press. https://doi.org/10.1093/ijnp/pyy094
Lally N, Nugent AC, Luckenbaugh DA, Ameli R, Roiser JP, Zarate CA (2014) Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression. Transl Psychiatry 4(10):e469. https://doi.org/10.1038/tp.2014.105
Lally N, Nugent AC, Luckenbaugh DA, Niciu MJ, Roiser JP, Zarate CA (2015) Neural correlates of change in major depressive disorder anhedonia following open-label ketamine. J Psychopharmacol 29(5):596–607. https://doi.org/10.1177/0269881114568041
Levchuk LA, Meeder EMG, Roschina OV, Loonen AJM, Boiko AS, Michalitskaya EV, Epimakhova EV, Losenkov IS, Simutkin GG, Bokhan NA, Schellekens AFA, Ivanova SA (2020) Exploring brain derived neurotrophic factor and cell adhesion molecules as biomarkers for the transdiagnostic symptom anhedonia in alcohol use disorder and comorbid depression. Front Psych 11:296. https://doi.org/10.3389/FPSYT.2020.00296/BIBTEX
Li N, Liu RJ, Dwyer JM, Banasr M, Lee B, Son H, Li XY, Aghajanian G, Duman RS (2011) Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psychiat 69(8):754–761. https://doi.org/10.1016/j.biopsych.2010.12.015
Li Y, Mou X, Jiang W, Yang Z, Shen X, Jin Z, Dai Z, Liu Y, Mao S, Zhang J, Yuan Y (2015) A comparative study of anhedonia components between major depression and schizophrenia in Chinese populations. Ann Gen Psychiatry 14(1):24. https://doi.org/10.1186/s12991-015-0061-3
Loas G, Lefebvre G, Rotsaert M, Englert Y (2018) Relationships between anhedonia, suicidal ideation and suicide attempts in a large sample of physicians. PLoS ONE 13(3):e0193619. https://doi.org/10.1371/journal.pone.0193619
Loureiro JRA, Leaver A, Vasavada M, Sahib AK, Kubicki A, Joshi S, Woods RP, Wade B, Congdon E, Espinoza R, Narr KL (2020) Modulation of amygdala reactivity following rapidly acting interventions for major depression. Hum Brain Mapp 41(7):1699–1710. https://doi.org/10.1002/hbm.24895
Mathews DC, Henter ID, Zarate CA (2012) Targeting the glutamatergic system to treat major depressive disorder: Rationale and progress to date. Drugs 72(10):1313–1333. https://doi.org/10.2165/11633130-000000000-00000
Mccloud TL, Caddy C, Jochim J, Rendell JM, Diamond PR, Shuttleworth C, Brett D, Amit BH, Mcshane R, Hamadi L, Hawton K, & Cipriani A (2015) Ketamine and other glutamate receptor modulators for depression in bipolar disorder in adults. In Cochrane Database of Systematic Reviews (2015, Issue 9). John Wiley and Sons Ltd. https://doi.org/10.1002/14651858.CD011611.pub2
McIntyre RS, Rodrigues NB, Lee Y, Lipsitz O, Subramaniapillai M, Gill H, Nasri F, Majeed A, Lui LM W, Senyk O, Phan L, Carvalho IP, Siegel A, Mansur RB, Brietzke E, Kratiuk K, Arekapudi AK, Abrishami A, Chau EH, … Rosenblat JD (2020) The effectiveness of repeated intravenous ketamine on depressive symptoms, suicidal ideation and functional disability in adults with major depressive disorder and bipolar disorder: results from the Canadian Rapid Treatment Center of Excellence. Journal of Affective Disorders, 274, 903–910. https://doi.org/10.1016/j.jad.2020.05.088
McIntyre RS, Rosenblat JD, Nemeroff CB, Sanacora G, Murrough JW, Berk M, Brietzke E, Dodd S, Gorwood P, Ho R, Iosifescu DV, Lopez Jaramillo C, Kasper S, Kratiuk K, Lee JG, Lee Y, Lui LMW, Mansur RB, Papakostas GI, … Stahl S (2021a) Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: an international expert opinion on the available evidence and implementation. American Journal of Psychiatry, appi.ajp.2020.2. https://doi.org/10.1176/appi.ajp.2020.20081251
McIntyre RS, Loft H, Christensen MC (2021b) Efficacy of vortioxetine on anhedonia: results from a pooled analysis of short-term studies in patients with major depressive disorder. Neuropsychiatr Dis Treat. https://doi.org/10.2147/NDT.S296451
McMakin DL, Olino TM, Porta G, Dietz LJ, Emslie G, Clarke G, Wagner KD, Asarnow JR, Ryan ND, Birmaher B, Shamseddeen W, Mayes T, Kennard B, Spirito A, Keller M, Lynch FL, Dickerson JF, Brent DA (2012) Anhedonia predicts poorer recovery among youth with selective serotonin reuptake inhibitor treatment-resistant depression. Journal of the American Academy of Child and Adolescent Psychiatry 51(4):404–411. https://doi.org/10.1016/J.JAAC.2012.01.011
Michaëlsson H, Andersson M, Svensson J, Karlsson L, Ehn J, Culley G, Engström A, Bergström N, Savvidi P, Kuhn HG, Hanse E, & Seth H (2019) The novel antidepressant ketamine enhances dentate gyrus proliferation with no effects on synaptic plasticity or hippocampal function in depressive-like rats. Acta Physiologica, 225(4). https://doi.org/10.1111/apha.13211
Morris LS, Costi S, Tan A, Stern ER, Charney DS, Murrough JW (2020) Ketamine normalizes subgenual cingulate cortex hyper-activity in depression. Neuropsychopharmacology 45(6):975–981. https://doi.org/10.1038/s41386-019-0591-5
Morris SE, & Cuthbert BN (2012) Research domain criteria: cognitive systems, neural circuits, and dimensions of behavior. Dialogues in Clinical Neuroscience 14(1) 29. https://doi.org/10.31887/DCNS.2012.14.1/SMORRIS
Naughton M, Clarke G, Oleary OF, Cryan JF, & Dinan TG (2014) A review of ketamine in affective disorders: current evidence of clinical efficacy, limitations of use and pre-clinical evidence on proposed mechanisms of action. In Journal of Affective Disorders (156 24–35). https://doi.org/10.1016/j.jad.2013.11.014
Nugent AC, Ballard ED, Gould TD, Park LT, Moaddel R, Brutsche NE, Zarate CA (2019) Ketamine has distinct electrophysiological and behavioral effects in depressed and healthy subjects. Mol Psychiatry 24(7):1040–1052. https://doi.org/10.1038/s41380-018-0028-2
Papp M, Gruca P, Lason-Tyburkiewicz M, Willner P (2017) Antidepressant, anxiolytic and procognitive effects of subacute and chronic ketamine in the chronic mild stress model of depression. Behav Pharmacol 28(1):1–8. https://doi.org/10.1097/FBP.0000000000000259
Perna G, Alciati A, Daccò S, Grassi M, & Caldirola D (2020) Personalized psychiatry and depression: the role of sociodemographic and clinical variables. Psychiatry Investigation 17(3) 193. https://doi.org/10.30773/PI.2019.0289
Pozzi L, Dorocic IP, Wang X, Carlén M, & Meletis K (2014) Mice lacking NMDA receptors in parvalbumin neurons display normal depression-related behavior and response to antidepressant action of NMDAR antagonists. PLoS ONE 9(1). https://doi.org/10.1371/journal.pone.0083879
Réus GZ, Carlessi AS, Titus SE, Abelaira HM, Ignácio ZM, da Luz JR, Matias BI, Bruchchen L, Florentino D, Vieira A, Petronilho F, Quevedo J (2015) A single dose of S-ketamine induces long-term antidepressant effects and decreases oxidative stress in adulthood rats following maternal deprivation. Dev Neurobiol 75(11):1268–1281. https://doi.org/10.1002/dneu.22283
Ritsner MS, Arbitman M, Lisker A (2011) Anhedonia is an important factor of health-related quality-of-life deficit in schizophrenia and schizoaffective disorder. Journal of Nervous and Mental Disease 199(11):845–853. https://doi.org/10.1097/NMD.0b013e3182349ce6
Rizvi SJ, Pizzagalli DA, Sproule BA, Kennedy SH (2016) Assessing anhedonia in depression: potentials and pitfalls. Neurosci Biobehav Rev 65:21–35. https://doi.org/10.1016/j.neubiorev.2016.03.004
Rodrigues NB, McIntyre RS, Lipsitz O, Cha DS, Lee Y, Gill H, Majeed A, Phan L, Nasri F, Ho R, Lin K, Subramaniapillai M, Kratiuk K, Mansur RB, Rosenblat JD (2020) Changes in symptoms of anhedonia in adults with major depressive or bipolar disorder receiving IV ketamine: results from the Canadian Rapid Treatment Center of Excellence. J Affect Disord 276:570–575. https://doi.org/10.1016/j.jad.2020.07.083
Sahib AK, Loureiro JRA, Vasavada MM, Kubicki A, Joshi SH, Wang K, Woods RP, Congdon E, Wang DJJ, Boucher ML, Espinoza R, Narr KL (2020) Single and repeated ketamine treatment induces perfusion changes in sensory and limbic networks in major depressive disorder. Eur Neuropsychopharmacol 33:89–100. https://doi.org/10.1016/j.euroneuro.2020.01.017
Sangkuhl K, Klein TE, Altman RB (2009) Selective serotonin reuptake inhibitors pathway. Pharmacogenet Genomics 19(11):907–909. https://doi.org/10.1097/FPC.0b013e32833132cb
Sarkar A, Kabbaj M (2016) Sex differences in effects of ketamine on behavior, spine density, and synaptic proteins in socially isolated rats. Biol Psychiat 80(6):448–456. https://doi.org/10.1016/j.biopsych.2015.12.025
Sasibhushana RB, Shankaranarayana Rao BS, Srikumar BN (2019) Repeated finasteride administration induces depression-like behavior in adult male rats. Behav Brain Res 365:185–189. https://doi.org/10.1016/j.bbr.2019.03.006
Serafini G, Howland RH, Rovedi F, Girardi P, Amore M (2014) The role of ketamine in treatment-resistant depression: a systematic review. Curr Neuropharmacol 12(5):444. https://doi.org/10.2174/1570159X12666140619204251
Sleigh J, Harvey M, Voss L, Denny B (2014) Ketamine - more mechanisms of action than just NMDA blockade. In Trends in Anaesthesia and Critical Care. https://doi.org/10.1016/j.tacc.2014.03.002
Thai M, Başgöze Z, Klimes-Dougan B, Mueller BA, Fiecas M, Lim KO, Albott CS, Cullen KR (2020) Neural and behavioral correlates of clinical improvement to ketamine in adolescents with treatment resistant depression. Front Psych 11:820. https://doi.org/10.3389/fpsyt.2020.00820
Thomas RK, Baker G, Lind J, Dursun S (2018) Rapid effectiveness of intravenous ketamine for ultraresistant depression in a clinical setting and evidence for baseline anhedonia and bipolarity as clinical predictors of effectiveness. J Psychopharmacol 32(10):1110–1117. https://doi.org/10.1177/0269881118793104
Tornese P, Sala N, Bonini D, Bonifacino T, La Via L, Milanese M, Treccani G, Seguini M, Ieraci A, Mingardi J, Nyengaard JR, Calza S, Bonanno G, Wegener G, Barbon A, Popoli M, & Musazzi L (2019) Chronic mild stress induces anhedonic behavior and changes in glutamate release, BDNF trafficking and dendrite morphology only in stress vulnerable rats. The rapid restorative action of ketamine. Neurobiology of Stress 10, 100160. https://doi.org/10.1016/j.ynstr.2019.100160
Treadway MT, Bossaller NA, Shelton RC, Zald DH (2012) Effort-based decision-making in major depressive disorder: a translational model of motivational anhedonia. J Abnorm Psychol. https://doi.org/10.1037/a0028813
Treadway MT, Zald DH (2011) Reconsidering anhedonia in depression: lessons from translational neuroscience. Neurosci Biobehav Rev 35(3):537. https://doi.org/10.1016/J.NEUBIOREV.2010.06.006
Trøstheim M, Eikemo M, Meir R, Hansen I, Paul E, Kroll SL, Garland EL, Leknes S (2020) Assessment of anhedonia in adults with and without mental illness: a systematic review and meta-analysis. JAMA Netw Open 3(8):2013233. https://doi.org/10.1001/jamanetworkopen.2020.13233
Vasavada MM, Loureiro J, Kubicki A, Sahib A, Wade B, Hellemann G, Espinoza RT, Congdon E, Narr KL, & Leaver AM (2020) Effects of serial ketamine infusions on corticolimbic functional connectivity in major depression. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. https://doi.org/10.1016/j.bpsc.2020.06.015
Vecchia DD, Kanazawa LKS, Wendler E, de Almeida Soares Hocayen P, Bruginski E, Campos FR, Stern CAJ, Vital MABF, Miyoshi E, Wöhr M, Schwarting RKW, & Andreatini R (2018) Effects of ketamine on vocal impairment, gait changes, and anhedonia induced by bilateral 6-OHDA infusion into the substantia nigra pars compacta in rats: therapeutic implications for Parkinson’s disease. Behavioural Brain Research 342, 1–10. https://doi.org/10.1016/j.bbr.2017.12.041
Vecchia DD, Kanazawa LKS, Wendler E, de Hocayen PAS, Vital M ABF, Takahashi RN, Da Cunha C, Miyoshi E, & Andreatini R (2021) Ketamine reversed short-term memory impairment and depressive-like behavior in animal model of Parkinson’s disease. Brain Research Bulletin 168, 63–73. https://doi.org/10.1016/j.brainresbull.2020.12.011
Walsh AEL, Huneke NTM, Brown R, Browning M, Cowen P, & Harmer CJ (2018) A dissociation of the acute effects of bupropion on positive emotional processing and reward processing in healthy volunteers. Frontiers in Psychiatry 9(OCT). https://doi.org/10.3389/FPSYT.2018.00482/FULL
Wardle MC, Vincent JN, Suchting R, Green CE, Lane SD, Schmitz JM (2017) Anhedonia is associated with poorer outcomes in contingency management for cocaine use disorder. J Subst Abuse Treat 72:32–39. https://doi.org/10.1016/j.jsat.2016.08.020
Weckmann K, Deery MJ, Howard JA, Feret R, Asara JM, Dethloff F, Filiou MD, Labermaier C, Maccarrone G, Lilley KS, Mueller M, Turck CW (2019) Ketamine’s effects on the glutamatergic and GABAergic systems: a proteomics and metabolomics study in mice. Complex Psychiatry 5(1):42–51. https://doi.org/10.1159/000493425
Wen G, Yao H, Li Y, Ding R, Ren X, Tan Y, Ren W, Yu H, Zhan X, Wang X, Xu E, Yao J, Zhang G, Lu Y, & Wu X (2019) Regulation of tau protein on the antidepressant effects of ketamine in the chronic unpredictable mild stress model. Frontiers in Psychiatry 10(APR). https://doi.org/10.3389/fpsyt.2019.00287
Winer ES, Drapeau CW, Veilleux JC, Nadorff MR (2016) The association between anhedonia, suicidal ideation, and suicide attempts in a large student sample. Arch Suicide Res 20(2):265–272. https://doi.org/10.1080/13811118.2015.1025119
Wright KN, Hagarty DP, Strong CE, Schoepfer KJ, Kabbaj M (2019) Sex-dependent ketamine addiction-like behavior profile following exposure to chronic mild stress. Chronic Stress 3:247054701983261. https://doi.org/10.1177/2470547019832613
Yang Y, Cui Y, Sang K, Dong Y, Ni Z, Ma S, Hu H (2018) Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature 554(7692):317–322. https://doi.org/10.1038/nature25509
Yin B, Thönes S, Cheng RK, Wang N, Covington HE, Meck WH (2016) Continuous social defeat induces depression-like symptoms including anhedonia and slowed time perception that are rapidly reversed by ketamine. Timing and Time Perception 4(4):371–397. https://doi.org/10.1163/22134468-00002077
Yokoyama R, Higuchi M, Tanabe W, Tsukada S, Naito M, Yamaguchi T, Chen L, Kasai A, Seiriki K, Nakazawa T, Nakagawa S, Hashimoto K, Hashimoto H, & Ago Y (2020) (S)-norketamine and (2S,6S)-hydroxynorketamine exert potent antidepressant-like effects in a chronic corticosterone-induced mouse model of depression. Pharmacology Biochemistry and Behavior, 191. https://doi.org/10.1016/j.pbb.2020.172876
Zanos P, Gould TD (2018) Mechanisms of ketamine action as an antidepressant. Mol Psychiatry 23(4):801–811. https://doi.org/10.1038/mp.2017.255
Zhuo C, Ji F, Tian H, Wang L, Jia F, Jiang D, Chen C, Zhou C, Lin X, & Zhu J (2020) Transient effects of multi-infusion ketamine augmentation on treatment-resistant depressive symptoms in patients with treatment-resistant bipolar depression – an open-label three-week pilot study. Brain and Behavior, 10(8). https://doi.org/10.1002/brb3.1674
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RSM has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC); speaker/consultation fees from Lundbeck, Janssen, Alkermes, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie, Atai Life Sciences. RSM is a CEO of Braxia Scientific Corp. JDR has received research grant support from the Canadian Cancer Society, Canadian Psychiatric Association, American Psychiatric Association, American Society of Psychopharmacology, University of Toronto, University Health Network Centre for Mental Health, Joseph M. West Family Memorial Fund and Timeposters Fellowship, and industry funding for speaker/consultation/research fees from Janssen, Allergan, Lundbeck, Sunovion, and COMPASS. JDR is the medical director of a private clinic providing intravenous ketamine infusions and intranasal esketamine for depression. LMWL is a contractor to Braxia Scientific. MV has within the last 3 years been a consultant for Lundbeck, Janssen Cilag, and Sunovion. All other authors have no conflicts of interest to disclose.
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Nogo, D., Jasrai, A.K., Kim, H. et al. The effect of ketamine on anhedonia: improvements in dimensions of anticipatory, consummatory, and motivation-related reward deficits. Psychopharmacology 239, 2011–2039 (2022). https://doi.org/10.1007/s00213-022-06105-9
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DOI: https://doi.org/10.1007/s00213-022-06105-9