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The treatment of resistant depression should be optimized aiming at complete remission of symptoms, a complex condition due to several factors. Approximately 1/3 of patients with depressive disorders do not even respond to available antidepressants. Consequently, new molecules with robust action, fast effects and sustained improvement are currently being researched worldwide. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has emerged as a promising alternative due to its involvement in neurogenesis, synaptogenesis and consequent rapid improvement of depressive and suicidal symptoms with traditional intravenous (IV) use in sub dose (0.5 mg / kg). The therapeutic response of IV use has been short and requires monitoring in a hospital setting. There are no studies evaluating response to long-term ketamine use. Recent research has focused on identifying other routes of ketamine use such as intranasal and intramuscular (IM). The use of ketamine IM, despite the fact that there are few studies and small samples, can demonstrate efficacy in acute treatment and maintenance of depression, as well as low profile of side effects, greater accessibility potential, reduced costs and risks, patient comfort and possible expansion of resistant depression treatment capabilities in different settings.
Compare the response of ketamine IM versus active control in treatment-resistant depression (TRD [primary outcome]) and find safety and tolerability of ketamine IM, evaluate changes in life quality, cognition and suicidal risk (secondary outcomes)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rapid-acting antidepressant | Experimental | Subjects eligible to participate in the study will receive IM ketamine and will use 2 placebo tablets as randomized. |
|
| Comparator | Active Comparator | Subjects eligible to participate in the study will receive IM saline and will use escitalopram 15 mg and aripiprazole 5 mg as randomized |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketamine | Drug | (0,75 mg/kg) saline solution (15 mg) Escitalopram (5 mg) Aripiprazole |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in depressive symptoms | Montomery-Åsberg Depression Rating Scale ([0-60] higher scores: worse outcome). No improvement: MADRS ≤ 25% Partial response: MADRS ≥ 25% and < 50% Response: MADRS ≥ 50% Remission: MADRS ≤10 | 3 times a week in once month (Phase II) |
| Change in depressive symptoms | Montgomery-Åsberg Depression Rating Scale ([0-60] higher scores: worse outcome). Recovery: Maintenance ≥ 6-8 months Relapse: Full return of symptoms once remission has occurred or worsening ≤ 75% with lower percentage of improvement (HAM-D inclusion criteria) | Once a week in six months (Phase III) |
| Change in depressive symptoms | Montgomery-Åsberg Depression Rating Scale ([0-60] higher scores: worse outcome). Relapse: Full return of symptoms once remission has occurred or worsening ≤ 75% with lower percentage of improvement (HAM-D inclusion criteria). | Once a week in once month (Phase IV) |
| Measure | Description | Time Frame |
|---|---|---|
| Depression symptoms | Hamiltom Depression Ratins Scale (HAM-D [0-50] higher scores: worse outcome). | Through study completion, an average of 1 year. |
| Clinical impressions-S | Clinical Global Impression Scale (CGI [0-7] higher scores: worse outcome). |
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Inclusion Criteria:
Diagnosis of TRD, according to clinical evaluation and confirmed by SCID-IV (Structured Clinical Interview for the DSM);
Moderate to severe intensity of the disease;
Female patients in fertile conditions should be using a clinically accepted contraceptive method (oral contraceptive and/or condom);
a. Blood test will be requested at the diagnostic stage and in case of clinical doubt as to the patient's gestational status,
Literate and able to understand the tasks requested;
With clinical comorbidities, however compensated;
Patients and/or legal representatives should understand the nature of the study and sign the Informed Consent Form.
Exclusion Criteria:
Imminent risk of suicide;
Patients with psychoactive substance dependence;
Intellectual deficit and psychotic symptoms;
Bipolar spectrum disorders and other primary psychiatric diagnoses;
Allergic to ketamine;
Glaucoma;
Treatment with reversible MAOI (monoamine oxidase inhibitor) in the week prior to visit 0;
Treatment with irreversible MAOI in two weeks prior to visit 0;
Fluoxetine treatment within 4 weeks prior to visit 0;
Treatment with others antidepressants;
Treatment with antipsychotics, lithium, benzodiazepines or other psychotropic drugs within 7 days prior to visit 0;
a. Lorazepam and zolpidem may be used;
Patients who become pregnant will be excluded from the study and referred for obstetric care.
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| Name | Affiliation | Role |
|---|---|---|
| Ricardo A Moreno, MD, PhD | Department and Institute of Psychiatry, University of Sao Paulo | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Núcleo de Pesquisas em Saúde Mental | Blumenau | Santa Catarina | 89.020-070 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17074942 | Result | Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905. | |
| 25305428 |
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Subjects will receive IM ketamine or IM saline applications as randomized. Applications will occur three times a week. It will be 4 weeks of IM application (12 initial applications). Injections will occur into the subjects' glutes (0.75 mg / kg). The ketamine group will use 2 placebo tablets and the parallel group escitalopram 15 mg and aripiprazole 5 mg. Thereafter, participants will receive weekly ketamine doses over 6 months as maintenance treatment. Research members will be submitted to Structured Clinical Interview for the DSM for diagnostic categorization and will be evaluated from other scales. Vital signs will be checked continuously for a period of 2 hours with each infusion. Patients will be observed in a quiet, comfortable room and subjected to medical monitoring for 2 hours. They will leave the environment in the company of a competent adult.
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| Cognition | Diagnostic Test | Composite tools |
|
| Suicide risk | Other | MADRS (10) and HAM-D (3) |
|
| Depression thoughts | Other | EPD |
|
| Quality of life and disability | Other | Quality of life and disability |
|
| Clinical and epidemiological factors | Other | Variables and categories |
|
| Safety of ketamine IM | Device | Vital signs |
|
| Tolerability of ketamine IM | Other | UKU-SERS, YOUNG, CADSS and BPRS-12. |
|
| Through study completion, an average of 1 year. |
| Clinical impressions-I | Clinical Global Impression Scale (CGI [0-7] higher scores: worse outcome). | Through study completion, an average of 1 year. |
| Electrocardiographic monitoring | P wave, PR interval, QRS complex, J-point, ST segment, T wave, Corrected QT interval and U wave Rhythm (irregular rhythm: worse outcome). | 3 times a week in once month (Fase II) and once a week in six months (Phase III) |
| Blood Pressure (BP [mmHg]). | BP low <90/60 (systolic/diastolic) mmHg and high >140/90 mmHg ( (systolic/diastolic). | 3 times a week in once month (Fase II) and once a week in six months (Phase III) |
| Heart rate (HR [bpm]). | Anormal HR <60 bpm or >100 bpm. | 3 times a week in once month (Fase II) and once a week in six months (Phase III) |
| Digital pulse oximetry (%). | Low oxygen saturation <95%. | 3 times a week in once month (Fase II) and once a week in six months (Phase III) |
| Respiratory rate (RR [cycles/min]) | Anormal RR <10 cycles/min or >20 cycles/min. | 3 times a week in once month (Fase II) and once a week in six months (Phase III) |
| Suicide risk 1 | Montgomery-Ã…sberg Depression Rating Scale (item 10 [0-6] higher scores: worse outcome). | Through study completion, an average of 1 year. |
| Suicide risk 2 | Hamilton Depression Rating Scale (item 3 [0-4] higher scores: worse outcome). | Through study completion, an average of 1 year. |
| General side effects | Ugvalg for Kliniske Undersgelser-Side Effect Rating Scale (UKU-SERS [48 specific symptoms).](streamdown:incomplete-link) | 3 times a week in once month (Phase II) and once a week in six months (Phase III) |
| Hypo/maniac symptoms | Young Mania Rating Scale (YOUNG [0-58] higher scores: worse outcome). | 3 times a week in once month (Phase II) and once a week in six months (Phase III) |
| Dissociative symptoms | Clinician-Administered Dissociative State Scale (CADSS [0-108] higher scores: worse outcome) | 3 times a week in once month (Phase II) and once a week in six months (Phase III) |
| Psychotic symptoms | Brief Psychiatric Rating Scale (item 12 [0-6] higher scores: worse outcome). | 3 times a week in once month (Phase II) and once a week in six months (Phase III) |
| Depression thoughts | Depression Thoughts Scale (EPD [1-78] higher scores: worse outcome) | Through study completion, an average of 1 year. |
| Stimate intelligence quocient | Wechsler Abreviated Scale of Intelligence (WASI [70-160 percentille] higher scores: better outcomes). | Through study completion, an average of 1 year. |
| Intelligence quocient | Wechsler Scale of Intelligence (WAIS III [70-155 percentille] higher scores: better outcomes). | Through study completion, an average of 1 year. |
| Attention | Trial Making Test (5-95 percentille, higher scores: better outcomes). | Through study completion, an average of 1 year. |
| Memory | Rey figures (10-100 percentille, higher scores: better outcomes) | Through study completion, an average of 1 year. |
| Executive functions 1 | Wisconsin Test (50->80 score, higher scores: better outcomes). | Through study completion, an average of 1 year. |
| Executive functions 2 | Stroop Color Word Test (5-95 percentille, higher scores: better outcomes) | Through study completion, an average of 1 year. |
| Verbal fluency 1 | Verbal Fluency Test (FAS [10-90 percentille], higher scores: better outcomes)) | Through study completion, an average of 1 year. |
| Verbal fluency 2 | The Rey Auditory-Verbal Learning Test (RAVLT [5-95 percentille], higher scores: better outcomes). | Through study completion, an average of 1 year. |
| Functional recovery 1 | World Health Organization Quality of Life (WHOQOL-brief [4 domains, 26 questions higher scores: better outcome]). | Through study completion, an average of 1 year. |
| Functional recovery 2 | Sheehan Disability Scale (SDS [0-30] higher scores: worse outcome). | Through study completion, an average of 1 year. |
| Body Mass Index (BMI) | Weight and height (kg/m2). | Through study completion, an average of 1 year. |
| Clinical and psychiatric features 1 | Disease intensity (HAM-D [% of patients], moderate or severe) | Through study completion, an average of 1 year. |
| Clinical and psychiatric features 2 | Number of episodes (questionnaire [incidence]) | Through study completion, an average of 1 year. |
| Clinical and psychiatric features 3 | Current episode duration (questionnaire [years]) | Through study completion, an average of 1 year. |
| Clinical and psychiatric features 4 | Suicide attempts (questionnaire [% of pacients]) | Through study completion, an average of 1 year. |
| Clinical and psychiatric features 5 | History of physical abuse (questionnaire [% of pacients]) | Through study completion, an average of 1 year. |
| Clinical and psychiatric features 6 | History of sexual abuse (questionnaire [% of pacients]) | Through study completion, an average of 1 year. |
| Clinical and psychiatric features 7 | Psychiatric hospitalizations (questionnaire [% of pacients]) | Through study completion, an average of 1 year. |
| Clinical and psychiatric features 8 | Clinical comorbidities (questionnaire [% of patients]). | Through study completion, an average of 1 year. |
| Clinical and psychiatric features 9 | Family history of depression (questionnaire [% of patients]) | Through study completion, an average of 1 year. |
| Clinical and psychiatric features 10 | Family history of bipolar disorders (questionnaire [% of patients)](streamdown:incomplete-link) | Through study completion, an average of 1 year. |
| Clinical and psychiatric features 11 | Family history of other mental disorders (questionnaire [% of patients]). | Through study completion, an average of 1 year. |
| Epidemiological features 1 | Age (questionnaire [years]). | Through study completion, an average of 1 year. |
| Epidemiological features 2 | Gender (questionnaire [% of patients]; male/female) | Through study completion, an average of 1 year. |
| Epidemiological features 3 | Marital status (questionnaire [% of patients] single, married, separated, divorced or widower). | Through study completion, an average of 1 year. |
| Epidemiological features 4 | Ethnicity (questionnaire [% of patients]) | Through study completion, an average of 1 year. |
| Epidemiological features 5 | Religion (questionnaire [% of patients] protestant, pentecostal or neopentecostal, spiritism, afro-brazilian, no religion or atheism and others]). | Through study completion, an average of 1 year. |
| Epidemiological features 6 | Occupation (questionnaire [% of patients]) | Through study completion, an average of 1 year. |
| Epidemiological features 7 | Education (questionnaire [years]) | Through study completion, an average of 1 year. |
| Epidemiological features 8 | Individual income (questionnaire [dollars]). | Through study completion, an average of 1 year. |
| Epidemiological features 9 | Family income (questionnaire [dollars]). | Through study completion, an average of 1 year. |
| Result |
| Bennabi D, Aouizerate B, El-Hage W, Doumy O, Moliere F, Courtet P, Nieto I, Bellivier F, Bubrovsky M, Vaiva G, Holztmann J, Bougerol T, Richieri R, Lancon C, Camus V, Saba G, Haesbaert F, d'Amato T, Charpeaud T, Llorca PM, Leboyer M, Haffen E. Risk factors for treatment resistance in unipolar depression: a systematic review. J Affect Disord. 2015 Jan 15;171:137-41. doi: 10.1016/j.jad.2014.09.020. Epub 2014 Oct 8. |
| 20151847 | Result | Philip NS, Carpenter LL, Tyrka AR, Price LH. Pharmacologic approaches to treatment resistant depression: a re-examination for the modern era. Expert Opin Pharmacother. 2010 Apr;11(5):709-22. doi: 10.1517/14656561003614781. |
| 27486148 | Result | Kennedy SH, Lam RW, McIntyre RS, Tourjman SV, Bhat V, Blier P, Hasnain M, Jollant F, Levitt AJ, MacQueen GM, McInerney SJ, McIntosh D, Milev RV, Muller DJ, Parikh SV, Pearson NL, Ravindran AV, Uher R; CANMAT Depression Work Group. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments. Can J Psychiatry. 2016 Sep;61(9):540-60. doi: 10.1177/0706743716659417. Epub 2016 Aug 2. |
| 25586212 | Result | Saveanu R, Etkin A, Duchemin AM, Goldstein-Piekarski A, Gyurak A, Debattista C, Schatzberg AF, Sood S, Day CV, Palmer DM, Rekshan WR, Gordon E, Rush AJ, Williams LM. The international Study to Predict Optimized Treatment in Depression (iSPOT-D): outcomes from the acute phase of antidepressant treatment. J Psychiatr Res. 2015 Feb;61:1-12. doi: 10.1016/j.jpsychires.2014.12.018. Epub 2014 Dec 31. |
| 23380715 | Result | Perlis RH. A clinical risk stratification tool for predicting treatment resistance in major depressive disorder. Biol Psychiatry. 2013 Jul 1;74(1):7-14. doi: 10.1016/j.biopsych.2012.12.007. Epub 2013 Feb 4. |
| 24314926 | Result | McIntyre RS, Filteau MJ, Martin L, Patry S, Carvalho A, Cha DS, Barakat M, Miguelez M. Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord. 2014 Mar;156:1-7. doi: 10.1016/j.jad.2013.10.043. Epub 2013 Nov 15. |
| 23554581 | Result | Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, Tsai AC. Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes. PLoS Med. 2013;10(3):e1001403. doi: 10.1371/journal.pmed.1001403. Epub 2013 Mar 12. |
| 25836356 | Result | Millan MJ, Goodwin GM, Meyer-Lindenberg A, Ove Ogren S. Learning from the past and looking to the future: Emerging perspectives for improving the treatment of psychiatric disorders. Eur Neuropsychopharmacol. 2015 May;25(5):599-656. doi: 10.1016/j.euroneuro.2015.01.016. Epub 2015 Feb 7. |
| 24223526 | Result | Ferrari AJ, Charlson FJ, Norman RE, Patten SB, Freedman G, Murray CJ, Vos T, Whiteford HA. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med. 2013 Nov;10(11):e1001547. doi: 10.1371/journal.pmed.1001547. Epub 2013 Nov 5. |
| 27733282 | Result | GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016 Oct 8;388(10053):1545-1602. doi: 10.1016/S0140-6736(16)31678-6. |
| 30025524 | Result | Machado MO, Veronese N, Sanches M, Stubbs B, Koyanagi A, Thompson T, Tzoulaki I, Solmi M, Vancampfort D, Schuch FB, Maes M, Fava GA, Ioannidis JPA, Carvalho AF. The association of depression and all-cause and cause-specific mortality: an umbrella review of systematic reviews and meta-analyses. BMC Med. 2018 Jul 20;16(1):112. doi: 10.1186/s12916-018-1101-z. |
| 27667656 | Result | Evans-Lacko S, Knapp M. Global patterns of workplace productivity for people with depression: absenteeism and presenteeism costs across eight diverse countries. Soc Psychiatry Psychiatr Epidemiol. 2016 Nov;51(11):1525-1537. doi: 10.1007/s00127-016-1278-4. Epub 2016 Sep 26. |
| 24789696 | Result | Mrazek DA, Hornberger JC, Altar CA, Degtiar I. A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996-2013. Psychiatr Serv. 2014 Aug 1;65(8):977-87. doi: 10.1176/appi.ps.201300059. |
| 23429808 | Result | Lepine BA, Moreno RA, Campos RN, Couttolenc BF. Treatment-resistant depression increases health costs and resource utilization. Braz J Psychiatry. 2012 Dec;34(4):379-88. doi: 10.1016/j.rbp.2012.05.009. |
| 18425072 | Result | Sanacora G, Zarate CA, Krystal JH, Manji HK. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov. 2008 May;7(5):426-37. doi: 10.1038/nrd2462. |
| 21827775 | Result | Sanacora G, Treccani G, Popoli M. Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders. Neuropharmacology. 2012 Jan;62(1):63-77. doi: 10.1016/j.neuropharm.2011.07.036. Epub 2011 Aug 3. |
| 25643025 | Result | Hillhouse TM, Porter JH. A brief history of the development of antidepressant drugs: from monoamines to glutamate. Exp Clin Psychopharmacol. 2015 Feb;23(1):1-21. doi: 10.1037/a0038550. |
| 26423481 | Result | Newport DJ, Carpenter LL, McDonald WM, Potash JB, Tohen M, Nemeroff CB; APA Council of Research Task Force on Novel Biomarkers and Treatments. Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression. Am J Psychiatry. 2015 Oct;172(10):950-66. doi: 10.1176/appi.ajp.2015.15040465. |
| 28649673 | Result | Hare BD, Ghosal S, Duman RS. Rapid Acting Antidepressants in Chronic Stress Models: Molecular and Cellular Mechanisms. Chronic Stress (Thousand Oaks). 2017 Feb;1. doi: 10.1177/2470547017697317. Epub 2017 Apr 10. |
| 25582770 | Result | Rasmussen KG. Has psychiatry tamed the "ketamine tiger?" Considerations on its use for depression and anxiety. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jan 4;64:218-24. doi: 10.1016/j.pnpbp.2015.01.002. Epub 2015 Jan 10. |
| 24388038 | Result | Naughton M, Clarke G, O'Leary OF, Cryan JF, Dinan TG. A review of ketamine in affective disorders: current evidence of clinical efficacy, limitations of use and pre-clinical evidence on proposed mechanisms of action. J Affect Disord. 2014 Mar;156:24-35. doi: 10.1016/j.jad.2013.11.014. Epub 2013 Dec 10. |
| 23295207 | Result | Dwyer JM, Duman RS. Activation of mammalian target of rapamycin and synaptogenesis: role in the actions of rapid-acting antidepressants. Biol Psychiatry. 2013 Jun 15;73(12):1189-98. doi: 10.1016/j.biopsych.2012.11.011. Epub 2013 Jan 4. |
| 21907221 | Result | Duman RS, Li N, Liu RJ, Duric V, Aghajanian G. Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology. 2012 Jan;62(1):35-41. doi: 10.1016/j.neuropharm.2011.08.044. Epub 2011 Sep 2. |
| 23732839 | Result | Akinfiresoye L, Tizabi Y. Antidepressant effects of AMPA and ketamine combination: role of hippocampal BDNF, synapsin, and mTOR. Psychopharmacology (Berl). 2013 Nov;230(2):291-8. doi: 10.1007/s00213-013-3153-2. Epub 2013 Jun 4. |
| 2650898 | Result | Reich DL, Silvay G. Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesth. 1989 Mar;36(2):186-97. doi: 10.1007/BF03011442. |
| 1308374 | Result | Haas DA, Harper DG. Ketamine: a review of its pharmacologic properties and use in ambulatory anesthesia. Anesth Prog. 1992;39(3):61-8. |
| 22516044 | Result | Zarate CA Jr, Brutsche N, Laje G, Luckenbaugh DA, Venkata SL, Ramamoorthy A, Moaddel R, Wainer IW. Relationship of ketamine's plasma metabolites with response, diagnosis, and side effects in major depression. Biol Psychiatry. 2012 Aug 15;72(4):331-8. doi: 10.1016/j.biopsych.2012.03.004. Epub 2012 Apr 18. |
| 23866089 | Result | Stahl SM. Mechanism of action of ketamine. CNS Spectr. 2013 Aug;18(4):171-4. doi: 10.1017/S109285291300045X. |
| 9928972 | Result | Green SM, Hummel CB, Wittlake WA, Rothrock SG, Hopkins GA, Garrett W. What is the optimal dose of intramuscular ketamine for pediatric sedation? Acad Emerg Med. 1999 Jan;6(1):21-6. doi: 10.1111/j.1553-2712.1999.tb00089.x. |
| 15800181 | Result | Bonanno G, Giambelli R, Raiteri L, Tiraboschi E, Zappettini S, Musazzi L, Raiteri M, Racagni G, Popoli M. Chronic antidepressants reduce depolarization-evoked glutamate release and protein interactions favoring formation of SNARE complex in hippocampus. J Neurosci. 2005 Mar 30;25(13):3270-9. doi: 10.1523/JNEUROSCI.5033-04.2005. |
| 21292242 | Result | Li N, Liu RJ, Dwyer JM, Banasr M, Lee B, Son H, Li XY, Aghajanian G, Duman RS. Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psychiatry. 2011 Apr 15;69(8):754-61. doi: 10.1016/j.biopsych.2010.12.015. Epub 2011 Feb 3. |
| 26630613 | Result | Vasavada MM, Leaver AM, Espinoza RT, Joshi SH, Njau SN, Woods RP, Narr KL. Structural connectivity and response to ketamine therapy in major depression: A preliminary study. J Affect Disord. 2016 Jan 15;190:836-841. doi: 10.1016/j.jad.2015.11.018. Epub 2015 Nov 18. |
| 10686270 | Result | Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9. |
| 23982301 | Result | Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013 Oct;170(10):1134-42. doi: 10.1176/appi.ajp.2013.13030392. |
| 24922494 | Result | Niciu MJ, Luckenbaugh DA, Ionescu DF, Guevara S, Machado-Vieira R, Richards EM, Brutsche NE, Nolan NM, Zarate CA Jr. Clinical predictors of ketamine response in treatment-resistant major depression. J Clin Psychiatry. 2014 May;75(5):e417-23. doi: 10.4088/JCP.13m08698. |
| 24821196 | Result | Lapidus KA, Levitch CF, Perez AM, Brallier JW, Parides MK, Soleimani L, Feder A, Iosifescu DV, Charney DS, Murrough JW. A randomized controlled trial of intranasal ketamine in major depressive disorder. Biol Psychiatry. 2014 Dec 15;76(12):970-6. doi: 10.1016/j.biopsych.2014.03.026. Epub 2014 Apr 3. |
| 24268616 | Result | Shiroma PR, Johns B, Kuskowski M, Wels J, Thuras P, Albott CS, Lim KO. Augmentation of response and remission to serial intravenous subanesthetic ketamine in treatment resistant depression. J Affect Disord. 2014 Feb;155:123-9. doi: 10.1016/j.jad.2013.10.036. Epub 2013 Oct 29. |
| 22840761 | Result | Murrough JW, Perez AM, Pillemer S, Stern J, Parides MK, aan het Rot M, Collins KA, Mathew SJ, Charney DS, Iosifescu DV. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry. 2013 Aug 15;74(4):250-6. doi: 10.1016/j.biopsych.2012.06.022. Epub 2012 Jul 27. |
| 27056608 | Result | Singh JB, Fedgchin M, Daly EJ, De Boer P, Cooper K, Lim P, Pinter C, Murrough JW, Sanacora G, Shelton RC, Kurian B, Winokur A, Fava M, Manji H, Drevets WC, Van Nueten L. A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression. Am J Psychiatry. 2016 Aug 1;173(8):816-26. doi: 10.1176/appi.ajp.2016.16010037. Epub 2016 Apr 8. |
| 29282469 | Result | Daly EJ, Singh JB, Fedgchin M, Cooper K, Lim P, Shelton RC, Thase ME, Winokur A, Van Nueten L, Manji H, Drevets WC. Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Feb 1;75(2):139-148. doi: 10.1001/jamapsychiatry.2017.3739. |
| 24688759 | Result | Caddy C, Giaroli G, White TP, Shergill SS, Tracy DK. Ketamine as the prototype glutamatergic antidepressant: pharmacodynamic actions, and a systematic review and meta-analysis of efficacy. Ther Adv Psychopharmacol. 2014 Apr;4(2):75-99. doi: 10.1177/2045125313507739. |
| 25010396 | Result | McGirr A, Berlim MT, Bond DJ, Fleck MP, Yatham LN, Lam RW. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol Med. 2015 Mar;45(4):693-704. doi: 10.1017/S0033291714001603. Epub 2014 Jul 10. |
| 26664100 | Result | Erratum: Acute Antidepressant Effects of Intramuscular Versus Intravenous Ketamine: Erratum. Indian J Psychol Med. 2015 Jul-Sep;37(3):379. doi: 10.4103/0253-7176.162911. |
| 19897179 | Result | aan het Rot M, Collins KA, Murrough JW, Perez AM, Reich DL, Charney DS, Mathew SJ. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry. 2010 Jan 15;67(2):139-45. doi: 10.1016/j.biopsych.2009.08.038. |
| 27028832 | Result | Loo CK, Galvez V, O'Keefe E, Mitchell PB, Hadzi-Pavlovic D, Leyden J, Harper S, Somogyi AA, Lai R, Weickert CS, Glue P. Placebo-controlled pilot trial testing dose titration and intravenous, intramuscular and subcutaneous routes for ketamine in depression. Acta Psychiatr Scand. 2016 Jul;134(1):48-56. doi: 10.1111/acps.12572. Epub 2016 Mar 30. |
| 35935445 | Derived | Cigognini MA, Guirado AG, van de Meene D, Schneider MA, Salomon MS, de Alexandria VS, Adriano JP, Thaler AM, Fernandes FDS, Carneiro A, Moreno RA. Intramuscular ketamine vs. escitalopram and aripiprazole in acute and maintenance treatment of patients with treatment-resistant depression: A randomized double-blind clinical trial. Front Psychiatry. 2022 Jul 22;13:830301. doi: 10.3389/fpsyt.2022.830301. eCollection 2022. |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D061218 | Depressive Disorder, Treatment-Resistant |
| ID | Term |
|---|---|
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D007649 | Ketamine |
| D000089983 | Escitalopram |
| D000068180 | Aripiprazole |
| D011788 | Quality of Life |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011437 | Propylamines |
| D000588 | Amines |
| D009570 | Nitriles |
| D001572 | Benzofurans |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006304 | Health Status |
| D003710 | Demography |
| D015991 | Epidemiologic Measurements |
| D011634 | Public Health |
| D004778 | Environment and Public Health |
Not provided
Not provided