Himmelseher S, Pfenninger E (December 1998). «[The clinical use of S-(+)-ketamine--a determination of its place]». Anästhesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie33 (12): 764-70. PMID9893910. doi:10.1055/s-2007-994851.
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 LM, Mansur RB, Papakostas GI, Subramaniapillai M, Thase M, Vieta E, Young AH, Zarate CA, Stahl S (May 2021). «Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation». Am J Psychiatry178 (5): 383-399. PMC9635017. PMID33726522. doi:10.1176/appi.ajp.2020.20081251. «A legitimate criticism, as it relates to interpreting the effect sizes reported with single or repeat-dose ketamine in TRD, is the possibility that nonspecific effects such as functional unblinding (e.g., by patients experiencing dissociation or euphoric responses) and expectancymayinadvertentlyinflate the efficacy of ketamine (51, 52). [...] Given the absence of an adequately designed head-to-head trial, the relative efficacies of intranasal esketamine and intravenous racemic ketamine are not known (65). [...] A recent meta-analysis comparing intranasal and intravenous ketamine formulations was unable to identify a significant difference between formulations as well as routes of delivery in efficacy at 24 hours, 7 days, and 28 days (17). A separate meta-analysis concluded that intravenous ketamine may be superior in efficacy and have lower dropout rates (66). However, it is difficult to draw definitive conclusions from these analyses given the heterogeneity across component studies.»
Ng J, Lui LM, Rosenblat JD, Teopiz KM, Lipsitz O, Cha DS, Xiong J, Nasri F, Lee Y, Kratiuk K, Rodrigues NB, Gill H, Subramaniapillai M, Mansur RB, Ho R, Cao B, McIntyre RS (April 2021). «Ketamine-induced urological toxicity: potential mechanisms and translation for adults with mood disorders receiving ketamine treatment». Psychopharmacology (Berl)238 (4): 917-926. PMID33484298. doi:10.1007/s00213-021-05767-1.
Horowitz MA, Moncrieff J (May 2020). «Are we repeating mistakes of the past? A review of the evidence for esketamine». Br J Psychiatry219 (5): 614-617. PMID32456714. doi:10.1192/bjp.2020.89.
Turner EH (December 2019). «Esketamine for treatment-resistant depression: seven concerns about efficacy and FDA approval». Lancet Psychiatry6 (12): 977-979. PMID31680014. doi:10.1016/S2215-0366(19)30394-3.
Paketci, Susan (November 2021). «Interpretation of the Montgomery–Åsberg Depression Rating Scale (MADRS)». The British Journal of Psychiatry219 (5): 620-621. ISSN0007-1250. PMID35048825. doi:10.1192/bjp.2021.162.
Muthukumaraswamy SD, Forsyth A, Lumley T (September 2021). «Blinding and expectancy confounds in psychedelic randomized controlled trials». Expert Rev Clin Pharmacol14 (9): 1133-1152. PMID34038314. doi:10.1080/17512433.2021.1933434.
Schenberg EE (October 2021). «Who is blind in psychedelic research? Letter to the editor regarding: blinding and expectancy confounds in psychedelic randomized controlled trials». Expert Rev Clin Pharmacol14 (10): 1317-1319. PMID34227438. doi:10.1080/17512433.2021.1951473.
Molero P, Ramos-Quiroga JA, Martin-Santos R, Calvo-Sánchez E, Gutiérrez-Rojas L, Meana JJ (May 2018). «Antidepressant Efficacy and Tolerability of Ketamine and Esketamine: A Critical Review». CNS Drugs32 (5): 411-420. PMID29736744. doi:10.1007/s40263-018-0519-3. «In brief, these studies (Table 1) have globally assessed responses to a single dose of intravenous ketamine in 166 patients with TDR with multiple treatment failures, including electroconvulsive therapy (ECT). The findings provide evidence of improvement in depressive symptoms within hours, with a response rate > 60% in the first 4.5 and 24 h, and > 40% after 7 days, with a big effect size in comparison with placebo (Cohen's d 1.3–1.7) or active placebo (midazolam, d = 0.8). These figures, though preliminary, contrast with the average effect size of conventional antidepressants (Cohen's d 0.53–0.81 in patients with intense symptoms) [32] and their response latency (about 4–7 weeks) [1].»
Singh I, Morgan C, Curran V, Nutt D, Schlag A, McShane R (May 2017). «Ketamine treatment for depression: opportunities for clinical innovation and ethical foresight». Lancet Psychiatry4 (5): 419-426. PMID28395988. doi:10.1016/S2215-0366(17)30102-5. «Ketamine has been hailed as the most important advance in the treatment of depression of the past 50 years.1».
Henter ID, Park LT, Zarate CA (May 2021). «Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status». CNS Drugs35 (5): 527-543. PMC8201267. PMID33904154. doi:10.1007/s40263-021-00816-x. «To date, only one study has examined the differences between esketamine (0.25 mg/kg) and (R,S)-ketamine (0.5 mg/kg); though underpowered, it found no differences in efficacy, tolerability, or psychotomimetic profile between the two agents [67]. A recent meta-analysis suggests the need to compare these two agents head-to-head [68].»
Correia-Melo FS, Leal GC, Vieira F, Jesus-Nunes AP, Mello RP, Magnavita G, Caliman-Fontes AT, Echegaray MV, Bandeira ID, Silva SS, Cavalcanti DE, Araújo-de-Freitas L, Sarin LM, Tuena MA, Nakahira C, Sampaio AS, Del-Porto JA, Turecki G, Loo C, Lacerda AL, Quarantini LC (March 2020). «Efficacy and safety of adjunctive therapy using esketamine or racemic ketamine for adult treatment-resistant depression: A randomized, double-blind, non-inferiority study». J Affect Disord264: 527-534. PMID31786030. doi:10.1016/j.jad.2019.11.086.
Hashimoto K (July 2020). «Molecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine». Biochem Pharmacol177: 113935. PMID32224141. doi:10.1016/j.bcp.2020.113935.
Sanders B, Brula AQ (May 2021). «Intranasal esketamine: From origins to future implications in treatment-resistant depression». J Psychiatr Res137: 29-35. PMID33647726. doi:10.1016/j.jpsychires.2021.02.020.
Himmelseher S, Pfenninger E (December 1998). «[The clinical use of S-(+)-ketamine--a determination of its place]». Anästhesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie(en alemán)33 (12): 764-70. PMID9893910. doi:10.1055/s-2007-994851.
Zhang JC, Li SX, Hashimoto K (January 2014). «R (-)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine». Pharmacology, Biochemistry, and Behavior116: 137-41. PMID24316345. doi:10.1016/j.pbb.2013.11.033.
Vollenweider FX, Leenders KL, Oye I, Hell D, Angst J (February 1997). «Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET)». European Neuropsychopharmacology7 (1): 25-38. PMID9088882. doi:10.1016/s0924-977x(96)00042-9.
Psychopharmacologic Drugs Advisory Committee (PDAC) and Drug Safety and Risk Management (DSaRM) Advisory Committee (12 de febrero de 2019). «FDA Briefing Document». Food and Drug Administration. Consultado el 12 de febrero de 2019. «Meeting, February 12, 2019. Agenda Topic: The committees will discuss the efficacy, safety, and risk-benefit profile of New Drug Application (NDA) 211243, esketamine 28 mg single-use nasal spray device, submitted by Janssen Pharmaceutica, for the treatment of treatment-resistant depression.»
fiercepharma.com
«J&J scores Spravato trial win in high-risk depression. Will doctors and payers buy in?». FiercePharma. 10 de septiembre de 2019. Consultado el 27 de noviembre de 2021. «Pricing, though, may still be an issue. In early May, the Institute for Clinical and Economic Review (ICER) declined to recommend Spravato for use at its steep list price of $32,400 per year. The U.S. cost watchdog said J&J would need to cut the sticker price between 25% and 52% to be considered cost-effective.»
Paketci, Susan (November 2021). «Interpretation of the Montgomery–Åsberg Depression Rating Scale (MADRS)». The British Journal of Psychiatry219 (5): 620-621. ISSN0007-1250. PMID35048825. doi:10.1192/bjp.2021.162.
Himmelseher S, Pfenninger E (December 1998). «[The clinical use of S-(+)-ketamine--a determination of its place]». Anästhesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie33 (12): 764-70. PMID9893910. doi:10.1055/s-2007-994851.
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 LM, Mansur RB, Papakostas GI, Subramaniapillai M, Thase M, Vieta E, Young AH, Zarate CA, Stahl S (May 2021). «Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation». Am J Psychiatry178 (5): 383-399. PMC9635017. PMID33726522. doi:10.1176/appi.ajp.2020.20081251. «A legitimate criticism, as it relates to interpreting the effect sizes reported with single or repeat-dose ketamine in TRD, is the possibility that nonspecific effects such as functional unblinding (e.g., by patients experiencing dissociation or euphoric responses) and expectancymayinadvertentlyinflate the efficacy of ketamine (51, 52). [...] Given the absence of an adequately designed head-to-head trial, the relative efficacies of intranasal esketamine and intravenous racemic ketamine are not known (65). [...] A recent meta-analysis comparing intranasal and intravenous ketamine formulations was unable to identify a significant difference between formulations as well as routes of delivery in efficacy at 24 hours, 7 days, and 28 days (17). A separate meta-analysis concluded that intravenous ketamine may be superior in efficacy and have lower dropout rates (66). However, it is difficult to draw definitive conclusions from these analyses given the heterogeneity across component studies.»
Khan A, Mar KF, Brown WA (June 2021). «Consistently Modest Antidepressant Effects in Clinical Trials: the Role of Regulatory Requirements». Psychopharmacol Bull51 (3): 79-108. PMC8374926. PMID34421147. «Even drugs with novel mechanisms of action such as the esketamine nasal spray show the same effect size and look nearly identical to other antidepressants when evaluated in the regulatory context (42% symptom reduction with placebo, 54% with drug, effect size 0.29). However, it must be taken under consideration that this trial was unique from the others in that it was an adjunctive study of esketamine nasal spray in treatment resistant patients. It is worth noting that two shortterm trials conducted for regulatory approval of esketamine but not included in the label did not reach statistical significance (P = 0.058 and P = 0.088).28 Independent analysis of these esketamine trial data submitted to the FDA show that despite expectations from smallscale preliminary studies, esketamine performs modestly in patients with treatment resistant depression in the context of large, regulatory trials.29 These authors also raised concerns about the potential lack of specificity of drug effects and the risk of side effects demonstrated in these trials. [...] False negatives are well-known risks of small sized studies. However, it is equally important to note that if we do not enroll adequate sample sizes we will continue run the serious risk of getting an inflated false positive resulting in an overestimate of treatment effects that is not replicable (as was the case with many of the earlier regulatory trials, which tended to have small sample sizes).25 This is especially pertinent for early pilot studies of investigational antidepressants (phase I and II trials), which are not always subject to the same regulatory statutes of later stage trials. This phenomenon is illustrated by the dramatic decline of treatment effect sizes seen with esketamine over the course of development (from small pilot studies to large regulatory trials). Although regulatory agencies allow for more lenient methods for exploratory purposes, this method may yield misleading conclusions because these small trials are invariably under-powered. Specifically, these exploratory trials may end up with an erroneously low placebo response and thus a falsely inflated estimate of effect size.46 This possibility is under appreciated by many investigators but should be strongly considered given the persistence of modest effect sizes in regulatory trials of antidepressants.»
Ng J, Lui LM, Rosenblat JD, Teopiz KM, Lipsitz O, Cha DS, Xiong J, Nasri F, Lee Y, Kratiuk K, Rodrigues NB, Gill H, Subramaniapillai M, Mansur RB, Ho R, Cao B, McIntyre RS (April 2021). «Ketamine-induced urological toxicity: potential mechanisms and translation for adults with mood disorders receiving ketamine treatment». Psychopharmacology (Berl)238 (4): 917-926. PMID33484298. doi:10.1007/s00213-021-05767-1.
Horowitz MA, Moncrieff J (May 2020). «Are we repeating mistakes of the past? A review of the evidence for esketamine». Br J Psychiatry219 (5): 614-617. PMID32456714. doi:10.1192/bjp.2020.89.
Turner EH (December 2019). «Esketamine for treatment-resistant depression: seven concerns about efficacy and FDA approval». Lancet Psychiatry6 (12): 977-979. PMID31680014. doi:10.1016/S2215-0366(19)30394-3.
Paketci, Susan (November 2021). «Interpretation of the Montgomery–Åsberg Depression Rating Scale (MADRS)». The British Journal of Psychiatry219 (5): 620-621. ISSN0007-1250. PMID35048825. doi:10.1192/bjp.2021.162.
Muthukumaraswamy SD, Forsyth A, Lumley T (September 2021). «Blinding and expectancy confounds in psychedelic randomized controlled trials». Expert Rev Clin Pharmacol14 (9): 1133-1152. PMID34038314. doi:10.1080/17512433.2021.1933434.
Schenberg EE (October 2021). «Who is blind in psychedelic research? Letter to the editor regarding: blinding and expectancy confounds in psychedelic randomized controlled trials». Expert Rev Clin Pharmacol14 (10): 1317-1319. PMID34227438. doi:10.1080/17512433.2021.1951473.
Molero P, Ramos-Quiroga JA, Martin-Santos R, Calvo-Sánchez E, Gutiérrez-Rojas L, Meana JJ (May 2018). «Antidepressant Efficacy and Tolerability of Ketamine and Esketamine: A Critical Review». CNS Drugs32 (5): 411-420. PMID29736744. doi:10.1007/s40263-018-0519-3. «In brief, these studies (Table 1) have globally assessed responses to a single dose of intravenous ketamine in 166 patients with TDR with multiple treatment failures, including electroconvulsive therapy (ECT). The findings provide evidence of improvement in depressive symptoms within hours, with a response rate > 60% in the first 4.5 and 24 h, and > 40% after 7 days, with a big effect size in comparison with placebo (Cohen's d 1.3–1.7) or active placebo (midazolam, d = 0.8). These figures, though preliminary, contrast with the average effect size of conventional antidepressants (Cohen's d 0.53–0.81 in patients with intense symptoms) [32] and their response latency (about 4–7 weeks) [1].»
Singh I, Morgan C, Curran V, Nutt D, Schlag A, McShane R (May 2017). «Ketamine treatment for depression: opportunities for clinical innovation and ethical foresight». Lancet Psychiatry4 (5): 419-426. PMID28395988. doi:10.1016/S2215-0366(17)30102-5. «Ketamine has been hailed as the most important advance in the treatment of depression of the past 50 years.1».
Henter ID, Park LT, Zarate CA (May 2021). «Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status». CNS Drugs35 (5): 527-543. PMC8201267. PMID33904154. doi:10.1007/s40263-021-00816-x. «To date, only one study has examined the differences between esketamine (0.25 mg/kg) and (R,S)-ketamine (0.5 mg/kg); though underpowered, it found no differences in efficacy, tolerability, or psychotomimetic profile between the two agents [67]. A recent meta-analysis suggests the need to compare these two agents head-to-head [68].»
Correia-Melo FS, Leal GC, Vieira F, Jesus-Nunes AP, Mello RP, Magnavita G, Caliman-Fontes AT, Echegaray MV, Bandeira ID, Silva SS, Cavalcanti DE, Araújo-de-Freitas L, Sarin LM, Tuena MA, Nakahira C, Sampaio AS, Del-Porto JA, Turecki G, Loo C, Lacerda AL, Quarantini LC (March 2020). «Efficacy and safety of adjunctive therapy using esketamine or racemic ketamine for adult treatment-resistant depression: A randomized, double-blind, non-inferiority study». J Affect Disord264: 527-534. PMID31786030. doi:10.1016/j.jad.2019.11.086.
Hashimoto K (July 2020). «Molecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine». Biochem Pharmacol177: 113935. PMID32224141. doi:10.1016/j.bcp.2020.113935.
Sanders B, Brula AQ (May 2021). «Intranasal esketamine: From origins to future implications in treatment-resistant depression». J Psychiatr Res137: 29-35. PMID33647726. doi:10.1016/j.jpsychires.2021.02.020.
Himmelseher S, Pfenninger E (December 1998). «[The clinical use of S-(+)-ketamine--a determination of its place]». Anästhesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie(en alemán)33 (12): 764-70. PMID9893910. doi:10.1055/s-2007-994851.
Zhang JC, Li SX, Hashimoto K (January 2014). «R (-)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine». Pharmacology, Biochemistry, and Behavior116: 137-41. PMID24316345. doi:10.1016/j.pbb.2013.11.033.
Doenicke A, Kugler J, Mayer M, Angster R, Hoffmann P (October 1992). «[Ketamine racemate or S-(+)-ketamine and midazolam. The effect on vigilance, efficacy and subjective findings]». Der Anaesthesist(en alemán)41 (10): 610-8. PMID1443509.
Pfenninger E, Baier C, Claus S, Hege G (November 1994). «[Psychometric changes as well as analgesic action and cardiovascular adverse effects of ketamine racemate versus s-(+)-ketamine in subanesthetic doses]». Der Anaesthesist(en alemán)43 (Suppl 2): S68-75. PMID7840417.
Vollenweider FX, Leenders KL, Oye I, Hell D, Angst J (February 1997). «Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET)». European Neuropsychopharmacology7 (1): 25-38. PMID9088882. doi:10.1016/s0924-977x(96)00042-9.
