Virtual Reality as an Adjunct to Ketamine Infusion Therapy Increases Patient Satisfaction in the Management of Chronic Pain and Depression: A Retrospective Pilot Study — Oak Academic Publishing
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Virtual Reality as an Adjunct to Ketamine Infusion Therapy Increases Patient Satisfaction in the Management of Chronic Pain and Depression: A Retrospective Pilot Study
Behavioral Neuroscience Program, Palm Beach Atlantic University, West Palm Beach, FL, USA
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Department of Psychology, Palm Beach Atlantic University, West Palm Beach, FL, USA
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Department of Pharmaceutical Sciences, Saint Joseph’s University, Philadelphia, PA, USA
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Manhattan Restorative Health Sciences, New York, NY, USA
1 Behavioral Neuroscience Program, Palm Beach Atlantic University, West Palm Beach, FL, USA
2 Department of Psychology, Palm Beach Atlantic University, West Palm Beach, FL, USA
3 Department of Pharmaceutical Sciences, Saint Joseph’s University, Philadelphia, PA, USA
4 Manhattan Restorative Health Sciences, New York, NY, USA
The management of patients with concomitant chronic pain (CP) and Major Depressive Disorder (MDD) remains challenging for clinicians. Current chronic pharmacologic management is often unsuccessful, or has intolerable side effects to the patients. While not restricted to patients with chronic pain, these patients are often diagnosed with depression, presenting with symptoms such as poor mood, anhedonia, and altered cognitive processes. It is estimated that a substantial proportion of treated patients do not derive a substantive benefit from traditional pharmacological treatments for depression. The present study involved a retrospective review of cases, exploring the patient-reported satisfaction with and tolerability of a novel use of virtual reality (VR), coined KVR, as an adjunct to intravenous ketamine infusion therapies. Specifically, the ketamine-virtual reality protocol was employed as a potential adjunctive intervention for patients suffering from chronic pain and depression. Visual Analog Scores (VAS) associated with pain were significantly lower on the third than on the first assessment day. Montgomery-Åsberg Depression Rating Scale (MADRS) scores improved following infusion and across days ( i.e. , sessions). Lastly, 2/3 of patients preferred the use of VR with their ketamine infusion. The results are considered in terms of implementing prospective studies to examine whether the combination therapies have a synergistic benefit and the nature and magnitude of clinically meaningful treatment effects, if any.
Dahlhamer, J., Lucas, J., Zelaya, C., Nahin, R., Mackey, S., DeBar, L., Kerns, R., Von Korff, M., Porter, L. and Helmick, C. (2018) Prevalence of Chronic Pain and High-Impact Chronic Pain Among Adults—United States, 2016. Morbidity and Mortality Weekly Report, 67, 1001-1006. https://doi.org/10.15585/mmwr.mm6736a2
Brunkow, A., Cannon, M., Graff, F.S., Martin, J.L., Hausmann, L.R.M. and McAndrew, L.M. (2020) Doctor Recommendations Are Related to Patient Interest and Use of Behavioral Treatment for Chronic Pain and Addiction. Journal of Pain, 21, 979-987. https://doi.org/10.1016/j.jpain.2019.12.008
Manchikanti, L., Fellows, B., Janata, J.W., Pampati, V., Grider, J.S. and Boswell, M.V. (2012) Opioid Epidemic in the United States. Pain Physician, 15, ES9-E38. https://doi.org/10.36076/ppj.2012/15/ES9
Dowell, D., Haegerich, T.M. and Chou, R. (2016) CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016. Journal of the American Medical Association, 315, 1624-1645. https://doi.org/10.1001/jama.2016.1464
Krebs, E.E., Gravely, A., Nugent, S., Jensen, A.C., DeRonne, B., Goldsmith, E.S., Kroenke, K., Bair, M.J. and Noorbaloochi, S. (2018) Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients with Chronic Back Pain or Hip or Knee Osteoarthritis Pain: The SPACE Randomized Clinical Trial. Journal of the American Medical Association, 319, 872-882. https://doi.org/10.1001/jama.2018.0899
Ramachandran, V.S. and Seckel, E.L. (2010) Using Mirror Visual Feedback and Virtual Reality to Treat fibromyalgia. Medical Hypotheses, 75, 495-496. https://doi.org/10.1016/j.mehy.2010.07.003
Ramachandran, V.S. and Blakeslee, S. (1998) Phantoms in the Brain. William Morrow, New York.
Defrin, R., Schreiber, S. and Ginzburg, K. (2015) Paradoxical Pain Perception in Posttraumatic Stress Disorder: The Unique Role of Anxiety and Dissociation. The Journal of Pain, 16, 961-970. https://doi.org/10.1016/j.jpain.2015.06.010
Moeller-Bertram, T., Keltner, J. and Strigo, I.A. (2012) Pain and Post-Traumatic Stress Disorder: Review of Clinical and Experimental Evidence. Neuropharmacology, 62, 586-597. https://doi.org/10.1016/j.neuropharm.2011.04.028
American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders. 5th Edition, American Psychiatric Association, Washington DC. https://doi.org/10.1176/appi.books.9780890425596
Conway, C.R., George, M.S. and Sackeim, H.A. (2017) Toward an Evidence-Based, Operational Definition of Treatment-Resistant Depression: When Enough Is Enough. JAMA Psychiatry, 74, 9-10. https://doi.org/10.1001/jamapsychiatry.2016.2586
Deutschenbaur, L., Beck, J., Kiyhankhadiv, A., Mühlhauser, M., Borgwardt, S., Walter, M., Hasler, G., Sollberger, D. and Lang, U.E. (2016) Role of Calcium, Glutamate and NMDA in Major Depression and Therapeutic Application. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 64, 325-333. https://doi.org/10.1016/j.pnpbp.2015.02.015
Henter, I.D., de Sousa, M.A., Teixeira, R. and Zarate Jr., C.A. (2018) Glutamatergic Modulators in Depression. Harvard Review of Psychiatry, 26, 307-319. https://doi.org/10.1097/HRP.0000000000000183
Murrough, J.W., Iosifescu, D.V., Chang, L.C., Al Jurdi, R.K., Green, C.E., Perez, A.M., Iqbal, S., Pillemer, S., Foulkes, A., Shah, A., Charney, D.S. and Mathew, S.J. (2013) Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial. American Journal of Psychiatry, 170, 1134-1142. https://doi.org/10.1176/appi.ajp.2013.13030392
Daly, E.J., Singh, J.B., Fedgchin, M., Cooper, K., Lim, P., Shelton, R.C., Thase, M.E., Winokur, A., Van Nueten, L., Manji, H. and Drevets, W.C. (2018) Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry, 75, 139-148. https://doi.org/10.1001/jamapsychiatry.2017.3739
Dahan, A., Olofsen, E., Sigtermans, M., Noppers, I., Niesters, M., Aarts, L., Bauer, M. and Sarton, E. (2011) Population Pharmacokinetic-Pharmacodynamic Modeling of Ketamine-Induced Pain Relief of Chronic Pain. European Journal of Pain, 15, 258-267. https://doi.org/10.1016/j.ejpain.2010.06.016
Ralph, Q., Paolino, C. and Meara, D. (2019) Subjective Changes in Mood and Chronic Pain Status-Post Intravenous Ketamine for Oral and Facial Surgery. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 128, e22. https://doi.org/10.1016/j.oooo.2019.02.250
Nejati, A., Jalili, M., Abbasi, S., Sarwari, F.T., Bidari, A., Ghajarzadeh, M. and Akhgar, A. (2019) Intranasal Ketamine Reduces Pain of Digital Nerve Block: A Double Blind Randomized Clinical Trial. American Journal of Emergency Medicine, 37, 1622-1626. https://doi.org/10.1016/j.ajem.2018.11.026
Eldufani, J., Nekoui, A. and Blaise, G. (2018) Nonanesthetic Effects of Ketamine: A Review Article. The American Journal of Medicine, 131, 1418-1424. https://doi.org/10.1016/j.amjmed.2018.04.029
Murrough, J.W., Abdallah, C.G. and Mathew, S.J. (2017) Targeting Glutamate Signalling in Depression: Progress and Prospects. Nature Reviews Drug Discovery, 16, 472-486. https://doi.org/10.1038/nrd.2017.16
Rush, A.J., Trivedi, M.H., Wisniewski, S.R., Nierenberg, A.A., Stewart, J.W., Warden, D., Niederehe, G., Thase, M.E., Lavori, P.W., Lebowitz, B.D., McGrath, P.J., Rosenbaum, J.F., Sackeim, H.A., Kupfer, D.J., Luther, J. and Fava M. (2006) Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report. American Journal of Psychiatry, 163, 1905-1917. https://doi.org/10.1176/ajp.2006.163.11.1905
Shiroma, P.R., Albott, C.S., Johns, B., Thuras, P., Wels, J. and Lim, K.O. (2014) Neurocognitive Performance and Serial Intravenous Subanesthetic Ketamine in Treatment-Resistant Depression. International Journal of Neuropsychopharmacology, 17, 1805-1813. https://doi.org/10.1017/S1461145714001011
Hess, E.M., Riggs, L.M., Michaelides, M. and Gould, T.D. (2022) Mechanisms of Ketamine and Its Metabolites as Antidepressants. Biochemical Pharmacology, 197, Article ID: 114892. https://doi.org/10.1016/j.bcp.2021.114892
Zanos P. and Gould, T.D. (2018) Mechanisms of Ketamine Action as an Antidepressant. Molecular Psychiatry, 23, 801-811. https://doi.org/10.1038/mp.2017.255
Zorumski, C.F., Izumi, Y. and Mennerick, S. (2016) Ketamine: NMDA Receptors and Beyond. Journal of Neuroscience, 44, 11158-11164. https://doi.org/10.1523/JNEUROSCI.1547-16.2016
Aleksandrova, L.R., Wang, Y.T. and Phillips, A.G. (2019) Evaluation of the Wistar-Kyoto Rat Model of Depression and the Role of Synaptic Plasticity in Depression and Antidepressant Response. Neuroscience and Biobehavioral Reviews, 105, 1-23. https://doi.org/10.1016/j.neubiorev.2019.07.007
Rincón-Cortés, M. and Grace, A.A. (2020) Antidepressant Effects of Ketamine on Depression-Related Phenotypes and Dopamine Dysfunction in Rodent Models of Stress. Behavioural Brain Research, 379, Article ID: 112367. https://doi.org/10.1016/j.bbr.2019.112367
Zhang, F., Luo, J. and Zhu, X. (2018) Ketamine Ameliorates Depressive-Like Behaviors by tPA-Mediated Conversion of proBDNF to mBDNF in the Hippocampus of Stressed Rats. Psychiatry Research, 269, 646-651. https://doi.org/10.1016/j.psychres.2018.08.075
Phillips, J.L., Norris, S., Talbot, J., Birmingham, M., Hatchard, T., Ortiz, A., Owoeye, O., Batten, L.A. and Blier, P. (2019) Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial. The American Journal of Psychiatry, 176, 401-409. https://doi.org/10.1176/appi.ajp.2018.18070834
Tashjian, V.C., Mosadeghi, S., Howard, A.R., Lopez, M., Dupuy, T., Reid, M., Martinez, B., Ahmed, S., Dailey, F., Robbins, K., Rosen, B., Fuller, G., Danovitch, I., IsHak, W. and Spiegel B. (2017) Virtual Reality for Management of Pain in Hospitalized Patients: Results of a Controlled Trial. JMIR Mental Health, 4, e9. https://doi.org/10.2196/mental.7387
Malloy, K. and Milling, L. (2010) The Effectiveness of Virtual Reality Distraction for Pain Reduction: A Systematic Review. Clinical Psychology Review, 30, 1011-1018. https://doi.org/10.1016/j.cpr.2010.07.001
Gold, J.I., Belmont, K.A. and Thomas, D.A. (2007) The Neurobiology of Virtual Reality Pain Attenuation. Cyber Psychology and Behavior, 10, 536-544. https://doi.org/10.1089/cpb.2007.9993
Hoffman, H.G., Richards, T.L., Bills, A.R., Van Oostrom, T., Magula, J., Seibel, E.J. and Sharar, S.R. (2006) Using FMRI to Study the Neural Correlates of Virtual Reality Analgesia. CNS Spectrums, 11, 45-51. https://doi.org/10.1017/S1092852900024202
Jones, T., Moore, T. and Choo, J. (2016) The Impact of Virtual Reality on Chronic Pain. PLOS ONE, 20, e0167523. https://doi.org/10.1371/journal.pone.0167523
Riva, G., Wiederhold, B.K. and Mantovani, F. (2019) Neuroscience of Virtual Reality: From Virtual Exposure to Embodied Medicine. Cyberpsychology, Behavior, and Social Networking, 22, 82-96. https://doi.org/10.1089/cyber.2017.29099.gri
Bell, R.F. and Kalso, E.A. (2018) Ketamine for Pain Management. PAIN Reports, 3, e674. https://doi.org/10.1097/PR9.0000000000000674
Lee, E.N. and Lee, J.H. (2016) The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis. PLOS ONE, 11, e0165461. https://doi.org/10.1371/journal.pone.0165461
Motov, S., Drapkin, J., Likourezos, A., Beals, T., Monfort, R., Fromm, C. and Marshall, J. (2018) Continuous Intravenous Sub-Dissociative Dose Ketamine Infusion for Managing Pain in the Emergency Department. Western Journal of Emergency Medicine, 19, 559-566. https://doi.org/10.5811/westjem.2017.12.36174
Glue, P., Neehoff, S., Sabadel, A., Broughton, L., Le Nedelec, M., Shadli, S., McNaughton, N. and Medlicott, N.J. (2019) Effects of Ketamine in Patients with Treatment-Refractory Generalized Anxiety and Social Anxiety Disorders: Exploratory Double-Blind Psychoactive-Controlled Replication Study. Journal of Psychopharmacology, 34, 267-272. https://doi.org/10.1177/0269881119874457
Miller, O.H., Moran, J.T. and Hall, B.J. (2016) Two Cellular Hypotheses Explaining the Initiation of Ketamine’s Antidepressant Actions: Direct Inhibition and Disinhibition. Neuropharmacology, 100, 17-26. https://doi.org/10.1016/j.neuropharm.2015.07.028
Thapa, Y.R. and Ren, Q. (2020) Recent Advances in Ketamine Research: An Update. Open Journal of Anesthesiology, 10, 89-100. https://doi.org/10.4236/ojanes.2020.103008
Jaracz, J., Gattner, K., Jaracz, K. and Górna, K. (2016) Unexplained Painful Physical Symptoms in Patients with Major Depressive Disorder: Prevalence, Pathophysiology and Management. CNS Drugs, 30, 293-304. https://doi.org/10.1007/s40263-016-0328-5
Nürnberger, M., Klingner, C., Witte, O.W. and Brodoehl, S. (2021) Mismatch of Visual-Vestibular Information in Virtual Reality: Is Motion Sickness Part of the Brains Attempt to Reduce the Prediction Error? Frontiers in Human Neuroscience, 15, Article 757735. https://doi.org/10.3389/fnhum.2021.757735
Montgomery, S.A. and Åsberg, M. (1979) A New Depression Scale Designed to Be Sensitive to Change. The British Journal of Psychiatry, 134, 382-389. https://doi.org/10.1192/bjp.134.4.382
Delgado, D.A., Lambert, B.S., Boutris, N., McCulloch, P.C., Robbins, A.B., Moreno, M.R. and Harris, J.D. (2018) Validation of Digital Visual Analog Scale Pain Scoring with a Traditional Paper-Based Visual Analog Scale in Adults. JAAOS: Global Research and Reviews, 2, e088. https://doi.org/10.5435/JAAOSGlobal-D-17-00088
Hawker, G.A., Mian, S., Kendzerska, T. and French, M. (2011) Measures of Adult Pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Research, 63, S240-S252. https://doi.org/10.1002/acr.20543
McCormack, H.M., Horne, D.J.L. and Sheather, S. (1988) Clinical Applications of Visual Analogue Scales: A Critical Review. Psychological Medicine, 18, 1007-1019. https://doi.org/10.1017/S0033291700009934
Coyle, C.M. and Laws, K.R. (2015) The Use of Ketamine as an Antidepressant: A Systematic Review and Meta-Analysis. Human Psychopharmacology: Clinical and Experimental, 30, 152-163. https://doi.org/10.1002/hup.2475
Fond, G., Loundou, A., Rabu, C., Macgregor, A., Lançon, C., Brittner, M., Micoulaud,-Franchi, J.A., Richieri, R., Courtet, P., Abbar, M., Roger, M., Leboyer, M. and Boyer, L. (2014) Ketamine Administration in Depressive Disorders: A Systematic Review and Meta-Analysis. Psychopharmacology, 231, 3663-3676. https://doi.org/10.1007/s00213-014-3664-5
Grady, S.E., Marsh, T.A., Tenhouse, A. and Klein, K. (2017) Ketamine for the Treatment of Major Depressive Disorder and Bipolar Depression: A Review of the Literature. Mental Health Clinician, 7, 16-23. https://doi.org/10.9740/mhc.2017.01.016
Kishimoto, T., Chawla, J.M., Hagi, K., Zarate, C.A., Kane, J.M., Bauer, M. and Correll, C.U. (2016) Single-Dose Infusion Ketamine and Non-Ketamine N-Methyl-D-Aspartate Receptor Antagonists for Unipolar and Bipolar Depression: A Meta-Analysis of Efficacy, Safety and Time Trajectories. Psychological Medicine, 46, 1459-1472. https://doi.org/10.1017/S0033291716000064
Xu, Y., Hackett, M., Carter, G., Loo, C., Gálvez, V., Glozier, N., Glue, P., Lapidus, K., McGirr, A., Somogyi, A.A., Mitchell, P.B. and Rodgers, A. (2015) Effects of Low-Dose and Very Low-Dose Ketamine among Patients with Major Depression: A Systematic Review and Meta-Analysis. International Journal of Neuropsychopharmacology, 19, pyv124. https://doi.org/10.1093/ijnp/pyv124
Carrougher, G.J., Hoffman, H.G., Nakamura, D., Lezotte, D., Soltani, M., Leahy, L., Engrav, L.H. and Patterson, D.R. (2009) The Effect of Virtual Reality on Pain and Range of Motion in Adults with Burn Injuries. Journal of Burn Care & Research, 30, 785-791. https://doi.org/10.1097/BCR.0b013e3181b485d3
Furman, E., Jasinevicius, T.R., Bissada, N.F., Victoroff, K.Z., Skillicorn, R. and Buchner, M. (2009) Virtual Reality Distraction for Pain Control during Periodontal Scaling and Root Planing Procedures. Journal of the American Dental Association, 140, 1508-1516. https://doi.org/10.14219/jada.archive.2009.0102
Garrett. B., Taverner, T., Masinde, W., Gromala, D., Shaw, C. and Negraeff, M.A. (2014) Rapid Evidence Assessment of Immersive Virtual Reality as an Adjunct Therapy in Acute Pain Management in Clinical Practice. Clinical Journal of Pain, 30, 1089-1098. https://doi.org/10.1097/AJP.0000000000000064
Morris, L.D., Louw, Q.A. and Crous, L.C. (2010) Feasibility and Potential Effect of a Low-Cost Virtual Reality System on Reducing Pain and Anxiety in Adult Burn Injury Patients during Physiotherapy in a Developing Country. Burns, 36, 659-664. https://doi.org/10.1016/j.burns.2009.09.005
Dascal, J., Reid, M., Ishak, W.W., Spiegel, B., Recacho, J., Rosen, B. and Danovitch, I. (2017) Virtual Reality and Medical Inpatients: A Systematic Review of Randomized Controlled Trials. Innovations in Clinical Neuroscience, 14, 14-21.
Jelen, L.A., Young, A.H. and Stone, J.M. (2021) Ketamine: A Tale of Two Enantiomers. Journal of Psychopharmacology, 35, 109-123. https://doi.org/10.1177/0269881120959644
Turner, E.H. (2019) Esketamine for Treatment-Resistant Depression: Seven Concerns about Efficacy and FDA Approval. The Lancet Psychiatry, 6, 977-979. https://doi.org/10.1016/S2215-0366(19)30394-3
Gastaldon, C., Papola, D., Ostuzzi, G. and Barbui, C. (2020) Esketamine for Treatment Resistant Depression: A Trick of Smoke and Mirrors? Epidemiology and Psychiatric Sciences, 29, e122. https://doi.org/10.1017/S204579602000027X
Horowitz, M.A. and Moncrieff, J. (2020) Are We Repeating Mistakes of the Past? A Review of the Evidence for Esketamine. British Journal of Psychiatry, 219, 614-617. https://doi.org/10.1192/bjp.2020.89
Meyer, J.S. and Quenzer, L.F. (2013) Psychopharmacology: Drugs, the Brain, and Behavior. Sinauer Associates, Sunderland.
Aronson, J.K. (2016) Ketamine. In: Aronson, A.S., Ed., Meyler’s Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions, Elsevier, Amsterdam, 406-412.
Green, S.M., Roback, M.G., Kennedy, R.M. and Krauss, B. (2011) Clinical Practice Guideline for Emergency Department Ketamine Dissociative Sedation: 2011 Update. Annals of Emergency Medicine, 57, 449-461. https://doi.org/10.1016/j.annemergmed.2010.11.030
Miller, O.H., Yang, L., Wang, C.C., Hargroder, E.A., Zhang, Y., Delpire, E. and Hall, B.J. (2014) GluN2B-Containing NMDA Receptors Regulate Depression-Like Behavior and Are Critical for the Rapid Antidepressant Actions of Ketamine. eLife, 3, e03581. https://doi.org/10.7554/eLife.03581.009
Bobo, W.V., Riva-Posse, P., Goes, F.S. and Parikh, S.V. (2020) Next-Step Treatment Considerations for Patients with Treatment-Resistant Depression That Responds to Low-Dose Intravenous Ketamine. Focus, 18, 181-192. https://doi.org/10.1176/appi.focus.20190048
Mandal, S., Sinha, V.K. and Goyal, N. (2019) Efficacy of Ketamine Therapy in the Treatment of Depression. Indian Journal of Psychiatry, 61, 480-485. https://doi.org/10.4103/psychiatry.IndianJPsychiatry_484_18
Marcantoni, W.S., Akoumba, B.S., Wassef, M., Mayrand, J., Lai, H., Richard-Devantoy, S. and Beauchamp, S. (2020) A Systematic Review and Meta-Analysis of the Efficacy of Intravenous Ketamine Infusion for Treatment Resistant Depression: January 2009-January 2019. Journal of Affective Disorders, 277, 831-841. https://doi.org/10.1016/j.jad.2020.09.007
Swainson, J., McGirr, A., Blier, P., Brietzke, E., Richard-Devantoy, S., Ravindran, N., Blier, J., Beaulieu, S., Frey, B.N., Kennedy, S.H., McIntyre, R.S., Milev, R.V., Parikh, S.V., Schaffer, A., Taylor, V.H., Tourjman, V., van Ameringen, M., Yatham, L.N., Ravindran, A.V. and Lam, R.W. (2020) The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder. Canadian Journal of Psychiatry, 66, 113-125. https://doi.org/10.1177/0706743720970860
Pocklington, A.J., Armstrong, J.D. and Grant, S.G.N. (2006) Organization of Brain Complexity-Synapse Proteome Form and Function. Briefings in Functional Genomics, 5, 66-73. https://doi.org/10.1093/bfgp/ell013
Hoffman, H.G., Doctor, J.N., Patterson, D.R., Carrougher, G.J. and Furness III, T.A. (2000) Virtual Reality as an Adjunctive Pain Control During Burn Wound Care in Adolescent Patients. Pain, 85, 305-309. https://doi.org/10.1016/S0304-3959(99)00275-4
Spiegel, B., Fuller, G., Lopez, M., Dupuy, T., Noah, B., Howard, A., Albert, M., Tashjian, V., Lam, R., Ahn, J., Dailey, F., Rosen, B.T., Vrahas, M., Little, M., Garlich, J., Dzubur, E., IsHak, W. and Danovitch, I. (2019) Virtual Reality for Management of Pain in Hospitalized Patients: A Randomized Comparative Effectiveness Trial. PLOS ONE, 14, e0219115. https://doi.org/10.1371/journal.pone.0219115
Maani, C.V., Hoffman, H.G., Fowler, M., Maiers, A.J., Gaylord, K.M. and DeSocio, P.A. (2011) Combining Ketamine and Virtual Reality Pain Control During Severe Burn Wound Care: One Military and One Civilian Patient. Pain Medicine, 12, 673-678. https://doi.org/10.1111/j.1526-4637.2011.01091.x
Li, A., Montano, Z., Chen, V.J. and Gold, J.I. (2011) Virtual Reality and Pain Management: Current Trends and Future Directions. Pain Management, 1, 147-157. https://doi.org/10.2217/pmt.10.15
Hoffman, H.G., Garcia-Palacios, A., Patterson, D.R., Jensen, M., Furness III, T. and Ammons Jr., W.F. (2001) The Effectiveness of Virtual Reality for Dental Pain Control: A Case Study. CyberPsychology and Behavior, 4, 527-535. https://doi.org/10.1089/109493101750527088
Rizzo, A.A., Difede, J., Rothbaum, B.O., Johnston, S., McLay, R.N., Reger, G., Gahm, G., Parsons, T., Graap, K. and Pair, J. (2009) VR PTSD Exposure Therapy Results with Active Duty OIF/OEF Combatants. Studies in Health Technology and Informatics, 142, 277-282.
Maples-Keller, J.L., Bunnell, B.E., Kim, S.J. and Rothbaum, B.O. (2017) The Use of Virtual Reality Technology in the Treatment of Anxiety and Other Psychiatric Disorders. Harvard Review of Psychiatry, 25, 103-113. https://doi.org/10.1097/HRP.0000000000000138
Maples-Keller, J.L., Yasinski, C., Manjin, N. and Rothbaum, B.O. (2017) Virtual Reality-Enhanced Extinction of Phobias and Post-Traumatic Stress. Neurotherapeutics, 14, 554-563. https://doi.org/10.1007/s13311-017-0534-y
Zhai, K., Dilawar, A., Yousef, M.S., Holroyd, S., El-Hammali, H. and Abdelmonem, M. (2021) Virtual Reality Therapy for Depression and Mood in Long-Term Care Facilities. Geriatrics, 6, Article 58. https://doi.org/10.3390/geriatrics6020058
Keppel, G. and Wickens, T.D. (2004) Design and Analysis: A Researcher’s Handbook. 4th Edition, Prentice Hall, New York.
Falk, E., Schlieper, D., van Caster, P., Lutterbeck, M.J., Schwartz, J., Cordes, J., Grau, I., Kienbaum, P. and Neukirchen, M. (2020) A Rapid Positive Influence of S-Ketamine on the Anxiety of Patients in Palliative Care: A Retrospective Pilot Study. BMC Palliative Care, 19, Article No. 1. https://doi.org/10.1186/s12904-019-0499-1
McGirr, A., Berlim, M.T., Bond, D.J., Fleck, M.P., Yatham, L.N. and Lam, R.W. (2015) A Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials of Ketamine in the Rapid Treatment of Major Depressive Episodes. Psychological Medicine, 45, 693-704. https://doi.org/10.1017/S0033291714001603