SUPPLEMENTAL MATERIAL SUPPLEMENTAL TABLE 1 EXCLUDED STUDIES AND REASONS

1 SUPPLEMENTAL TABLE THE EMPYREAN STUDY COMMITTEES PRINCIPAL INVESTIGATOR
11 SUPPLEMENTAL FIGURES SF1 SAMPLES CLUSTER BY STRAIN PLOT
2170463 §217046—ELIGIBILITY FOR SUPPLEMENTAL EDUCATIONAL ASSISTANCE 2170463 §217046 ELIGIBILITY

3 SUPPLEMENTAL TABLE 1 PARTIAL CORRELATIONS† BETWEEN DIETARY FACTORS‡
7 SUPPLEMENTAL INFORMATION VAKIFAHMETOGLUNORBERG ET AL SUPPLEMENTAL INFORMATION SUPPLEMENTAL
7 TABLE 1 SUPPLEMENTAL INFORMATION ON THE ANALYZED STUDIES

Supplemental Material

Supplemental Table 1. Excluded studies and reasons.

Study	Reason
aan het Rot et al, 2010	Open-label
Bastos et al, 2012	Abstract only; Correspondence with authors did not yield the data required to compute response rates or effect sizes
Blier, 2013	Review
Blier et al, 2012	Review
Burgdorf et al, 2013	Ketamine in title but not used in trial
Carlson et al, 2013	Open-label
Carrier et al, 2013	Animal research
Cornwell et al, 2012	Open-label
Correll et al, 2006	Case report
Cusin et al, 2012	Case report
Diazgranados et al, 2010	Open-label
Duncan et al, 2013	Open-label
Duncan et al, 2013	Open-label
Ghasemi et al, in press	Single-blind; Randomization procedure not described
Gosek et al, 2012	Review; Written in Polish
Hashimoto, 2012	Review
Ibrahim et al, 2011	Open-label
Ibrahim et al, 2012	Open-label (secondary use of data from an RCT of riluzole, ketamine portion open-label)
Irwin et al, 2010	Case report
Irwin et al, 2013	Open-label
Kollmar et al, 2008	Case report
Kudoh et al, 2002	HDRS score “self-report”; No information pertaining to blinding
Laje et al, 2012	Open-label
Larkin et al, 2011	Open-label
Luckenbaugh et al, 2012	Secondary analysis of published data
Machado-Viera et al, 2009	Open-label
Matthew et al, 2010	Open-label (RCT of riluzole, ketamine portion open-label)
Messer et al, 2010	Case report
Murrough et al, 2013	Open-label
Paslakis et al, 2010	Case report
Phelps et al, 2009	Open-label (secondary use of data from an RCT of riluzole, RCT of riluzole, ketamine portion open-label)
Price et al, 2009	Open-label

Supplementary Table 2. Trial evaluation using the Cochrane Collaboration’s Tool for Assessing

Study	Selection Bias	Performance Bias	Detection Bias	Attrition Bias	Reporting Bias	Other Bias
Berman et al, 2000	Unclear	Low	High	Low	Low	Placebo Adequacy Unclear
Zarate et al, 2006	Low	Low	High	Low	Low	Placebo Adequacy Unclear
Diazgranados et al, 2010	Low	Low	High	Low	Low	Placebo Adequacy Unclear
Zarate et al, 2012	Low	Low	High	Low	Low	Placebo Adequacy Unclear
Sos et al, 2013	Unclear/Low	Unclear	High	Low	Low	Placebo Adequacy Unclear
Murrough et al, 2013	Unclear/Low	Low	Unclear	Low	Low	Placebo Adequacy Unclear
Lapidus et al, in press	Low	Low	Unclear	Low	Low	Placebo Adequacy Unclear

Risk of Bias.

Database search

MEDLINE: search date January 14^th, 2014

EMBASE: search date January 14^th, 2014

PsycINFO: search date December 23^rd, 2013

Cochrane Central Register of Controlled Trials (CENTRAL): search date January 14^th, 2014

Supplemental Figure 1. MEDLINE (OVID interface) search strategy and results.

SUPPLEMENTAL MATERIAL SUPPLEMENTAL TABLE 1 EXCLUDED STUDIES AND REASONS

Supplemental Figure 2. EMBASE (Ovid Interface) search strategy and results.

SUPPLEMENTAL MATERIAL SUPPLEMENTAL TABLE 1 EXCLUDED STUDIES AND REASONS

Supplemental Figure 3. CENTRAL (Ovid Interface) search strategy and results.

SUPPLEMENTAL MATERIAL SUPPLEMENTAL TABLE 1 EXCLUDED STUDIES AND REASONS

Supplemental Figure 4. PsychINFO (Ovid Interface) search strategy and results.

SUPPLEMENTAL MATERIAL SUPPLEMENTAL TABLE 1 EXCLUDED STUDIES AND REASONS

Supplemental Figure 5. Standardized mean differences for A) the Brief Psychiatric Rating Scale (BPRS) at 40-60 minutes post-infusion and B) the Clinician Administered Dissociation States Scale (CADSS) at 40 minutes post-infusion.

Supplemental Figure 6. Funnel Plots of clinical remission.

Supplemental Figure 7. Funnel Plots of clinical response.

Supplemental Figure 8. Funnel Plot for standardized mean difference in clinician rated depression score at 24 hours.

References

aan het Rot, M., Collins, K. A., Murrough, J. W., Perez, A. M., Reich, D. L., Charney, D. S. & Mathew, S. J. (2010). Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry 67, 139-45.

Bastos, M., Pereira, M. & Pereira, E. (2012). Effects of intra-operative sedation with low-doses of s-ketamine on depression: Randomized double-blind controlled trial. In WFSA World Congress of Anaesthesiologists Predio Ferial de Buenos Aires Argentina.

Blier, P. (2013). Exploiting N-methyl-d-aspartate channel blockade for a rapid antidepressant response in major depressive disorder. Biol Psychiatry 74, 238-9.

Blier, P., Zigman, D. & Blier, J. (2012). On the safety and benefits of repeated intravenous injections of ketamine for depression. Biol Psychiatry 72, e11-2.

Burgdorf, J., Zhang, X. L., Nicholson, K. L., Balster, R. L., Leander, J. D., Stanton, P. K., Gross, A. L., Kroes, R. A. & Moskal, J. R. (2013). GLYX-13, a NMDA receptor glycine-site functional partial agonist, induces antidepressant-like effects without ketamine-like side effects. Neuropsychopharmacology 38, 729-42.

Carrier, N. & Kabbaj, M. (2013). Sex differences in the antidepressant-like effects of ketamine. Neuropharmacology 70, 27-34.

Cornwell, B. R., Salvadore, G., Furey, M., Marquardt, C. A., Brutsche, N. E., Grillon, C. & Zarate, C. A., Jr. (2012). Synaptic potentiation is critical for rapid antidepressant response to ketamine in treatment-resistant major depression. Biol Psychiatry 72, 555-61.

Correll, G. E. & Futter, G. E. (2006). Two case studies of patients with major depressive disorder given low-dose (subanesthetic) ketamine infusions. Pain Med 7, 92-5.

Cusin, C., Hilton, G. Q., Nierenberg, A. A. & Fava, M. (2012). Long-term maintenance with intramuscular ketamine for treatment-resistant bipolar II depression. Am J Psychiatry 169, 868-9.

DiazGranados, N., Ibrahim, L. A., Brutsche, N. E., Ameli, R., Henter, I. D., Luckenbaugh, D. A., Machado-Vieira, R. & Zarate, C. A., Jr. (2010). Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry 71, 1605-11.

Duncan, W. C., Jr., Selter, J., Brutsche, N., Sarasso, S. & Zarate, C. A., Jr. (2013a). Baseline delta sleep ratio predicts acute ketamine mood response in major depressive disorder. J Affect Disord 145, 115-9.

Duncan, W. C., Sarasso, S., Ferrarelli, F., Selter, J., Riedner, B. A., Hejazi, N. S., Yuan, P., Brutsche, N., Manji, H. K., Tononi, G. & Zarate, C. A. (2013b). Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder. Int J Neuropsychopharmacol 16, 301-11.

Gosek, P., Chojnacka, M., Bienkowski, P. & Swiecicki, L. (2012). [Antidepressant effect of ketamine, a N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, in the therapy of treatment-resistant depression]. Psychiatr Pol 46, 283-94.

Hashimoto, K. (2012). A BDNF Val66Met Polymorphism and Ketamine-induced Rapid Antidepressant Action. Clin Psychopharmacol Neurosci 10, 59-60.

Ibrahim, L., Diazgranados, N., Franco-Chaves, J., Brutsche, N., Henter, I. D., Kronstein, P., Moaddel, R., Wainer, I., Luckenbaugh, D. A., Manji, H. K. & Zarate, C. A., Jr. (2012). Course of improvement in depressive symptoms to a single intravenous infusion of ketamine vs add-on riluzole: results from a 4-week, double-blind, placebo-controlled study. Neuropsychopharmacology 37, 1526-33.

Ibrahim, L., Diazgranados, N., Luckenbaugh, D. A., Machado-Vieira, R., Baumann, J., Mallinger, A. G. & Zarate, C. A., Jr. (2011). Rapid decrease in depressive symptoms with an N-methyl-d-aspartate antagonist in ECT-resistant major depression. Prog Neuropsychopharmacol Biol Psychiatry 35, 1155-9.

Irwin, S. A. & Iglewicz, A. (2010). Oral ketamine for the rapid treatment of depression and anxiety in patients receiving hospice care. J Palliat Med 13, 903-8.

Irwin, S. A., Iglewicz, A., Nelesen, R. A., Lo, J. Y., Carr, C. H., Romero, S. D. & Lloyd, L. S. (2013). Daily oral ketamine for the treatment of depression and anxiety in patients receiving hospice care: a 28-day open-label proof-of-concept trial. J Palliat Med 16, 958-65.

Kollmar, R., Markovic, K., Thurauf, N., Schmitt, H. & Kornhuber, J. (2008). Ketamine followed by memantine for the treatment of major depression. Aust N Z J Psychiatry 42, 170.

Kudoh, A., Takahira, Y., Katagai, H. & Takazawa, T. (2002). Small-dose ketamine improves the postoperative state of depressed patients. Anesth Analg 95, 114-8, table of contents.

Laje, G., Lally, N., Mathews, D., Brutsche, N., Chemerinski, A., Akula, N., Kelmendi, B., Simen, A., McMahon, F. J., Sanacora, G. & Zarate, C., Jr. (2012). Brain-derived neurotrophic factor Val66Met polymorphism and antidepressant efficacy of ketamine in depressed patients. Biol Psychiatry 72, e27-8.

Larkin, G. L. & Beautrais, A. L. (2011). A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department. Int J Neuropsychopharmacol 14, 1127-31.

Luckenbaugh, D. A., Ibrahim, L., Brutsche, N., Franco-Chaves, J., Mathews, D., Marquardt, C. A., Cassarly, C. & Zarate, C. A., Jr. (2012). Family history of alcohol dependence and antidepressant response to an N-methyl-D-aspartate antagonist in bipolar depression. Bipolar Disord 14, 880-7.

Machado-Vieira, R., Yuan, P., Brutsche, N., DiazGranados, N., Luckenbaugh, D., Manji, H. K. & Zarate, C. A., Jr. (2009). Brain-derived neurotrophic factor and initial antidepressant response to an N-methyl-D-aspartate antagonist. J Clin Psychiatry 70, 1662-6.

Mathew, S. J., Murrough, J. W., aan het Rot, M., Collins, K. A., Reich, D. L. & Charney, D. S. (2010). Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial. Int J Neuropsychopharmacol 13, 71-82.

Messer, M., Haller, I. V., Larson, P., Pattison-Crisostomo, J. & Gessert, C. E. (2010). The use of a series of ketamine infusions in two patients with treatment-resistant depression. J Neuropsychiatry Clin Neurosci 22, 442-4.

Murrough, J. W., Perez, A. M., Pillemer, S., Stern, J., Parides, M. K., aan het Rot, M., Collins, K. A., Mathew, S. J., Charney, D. S. & Iosifescu, D. V. (2013). Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry 74, 250-6.

Paslakis, G., Gilles, M., Meyer-Lindenberg, A. & Deuschle, M. (2010). Oral administration of the NMDA receptor antagonist S-ketamine as add-on therapy of depression: a case series. Pharmacopsychiatry 43, 33-5.

Phelps, L. E., Brutsche, N., Moral, J. R., Luckenbaugh, D. A., Manji, H. K. & Zarate, C. A., Jr. (2009). Family history of alcohol dependence and initial antidepressant response to an N-methyl-D-aspartate antagonist. Biol Psychiatry 65, 181-4.

Price, R. B., Nock, M. K., Charney, D. S. & Mathew, S. J. (2009). Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biol Psychiatry 66, 522-6.

Achievement Goals 7 Supplemental Materials in Their own Words
ANNEX II SUPPLEMENTAL STATUTORY DECLARATION IN THE MATTER
ANNOUNCEMENT REQUEST FOR PROPOSAL GROUP LIFEDISABILITYSUPPLEMENTAL LIFE DECEMBER 2017

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