Rapid Onset of Intranasal Esketamine in Patients with Treatment Resistant Depression and Major Depression with Suicide Ideation: A Meta-Analysis
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Objective: We performed a meta-analysis of randomized double-blinded placebo controlled trials (DB-RCTs) to investigate efficacy and safety of intranasal esketamine in treating major depressive disorder (MDD) including treatment resistant depression (TRD) and major depression with suicide ideation (MDSI). Methods: Mean change in total scores on Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to different time-points were our primary outcome measure. Secondary efficacy measures included rate of remission of depression and resolution of suicidality. Results: Eight DB-RCTs (seven published and one un-published) covering 1,488 patients with MDD were included. Esketamine more significantly improved MADRS total scores than placebo starting from 2−4 hours after the first administration (standardized mean difference, −0.41 [95% CI, −0.58 to −0.25], p ＜ 0.00001), and this superiority maintained until end of double-blinded period (28 days). Sub-group analysis showed that superior antidepressant effects of esketamine over placebo in TRD and MDSI was observed from 2−4 hours, which was maintained until 28 days. Resolution of suicide in MDSI was also greater for esketamine than for placebo at 2−4 hours (OR of 2.04, 95% CIs, 1.37 to 3.05, p = 0.0005), but two groups did not statistically differ at 24 hours and day 28. Total adverse events (AEs), and other common AEs including dissociation, blood pressure increment, nausea, vertigo, dysgeusia, dizziness, and somnolence were more frequent in esketamine than in placebo group. Conclusion: Esketamine showed rapid antidepressant effects in patients with MDD, including TRD and MDSI. The study also suggested that esketamine might be associated with rapid anti-suicidal effects for patients with MDSI.
Abstract
Objective: We performed a meta-analysis of randomized double-blinded placebo controlled trials (DB-RCTs) to investigate efficacy and safety of intranasal esketamine in treating major depressive disorder (MDD) including treatment resistant depression (TRD) and major depression with suicide ideation (MDSI). Methods: Mean change in total scores on Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to different time-points were our primary outcome measure. Secondary efficacy measures included rate of remission of depression and resolution of suicidality. Results: Eight DB-RCTs (seven published and one un-published) covering 1,488 patients with MDD were included. Esketamine more significantly improved MADRS total scores than placebo starting from 2−4 hours after the first administration (standardized mean difference, −0.41 [95% CI, −0.58 to −0.25], p ＜ 0.00001), and this superiority maintained until end of double-blinded period (28 days). Sub-group analysis showed that superior antidepressant effects of esketamine over placebo in TRD and MDSI was observed from 2−4 hours, which was maintained until 28 days. Resolution of suicide in MDSI was also greater for esketamine than for placebo at 2−4 hours (OR of 2.04, 95% CIs, 1.37 to 3.05, p = 0.0005), but two groups did not statistically differ at 24 hours and day 28. Total adverse events (AEs), and other common AEs including dissociation, blood pressure increment, nausea, vertigo, dysgeusia, dizziness, and somnolence were more frequent in esketamine than in placebo group. Conclusion: Esketamine showed rapid antidepressant effects in patients with MDD, including TRD and MDSI. The study also suggested that esketamine might be associated with rapid anti-suicidal effects for patients with MDSI.
참고문헌 (35)
- Kessler RC, "Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States", Int J Methods Psychiatr Res, 21, pp.169~184 (2012)
- Chiara Fabbri, "Genetics of Treatment Outcomes in Major Depressive Disorder: Present and Future", Clinical Psychopharmacology and Neuroscience, 18(1), pp.1~9 (2020), 대한정신약물학회[DOI]
- Fava M, "Diagnosis and definition of treatment-resistant depression", Biol Psychiatry, 53, pp.649~659 (2003)
- Rush AJ, "Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps : a STAR*D report", Am J Psychiatry, 163, pp.1905~1917 (2006)
- Chiara Fabbri, "How to Utilize Clinical and Genetic Information for Personalized Treatment of Major Depressive Disorder: Step by Step Strategic Approach", Clinical Psychopharmacology and Neuroscience, 18(4), pp.484~492 (2020), 대한정신약물학회[DOI]
- Blair-West GW, "Lifetime suicide risk in major depression : sex and age determinants", J Affect Disord, 55, pp.171~178 (1999)
- Hasin DS, "Epidemiology of adult DSM-5 major depressive disorder and its specifiers in the United States", JAMA Psychiatry, 75, pp.336~346 (2018)
- Leon AC, "Antidepressants and risks of suicide and suicide attempts : a 27-year observational study", J Clin Psychiatry, 72, pp.580~586 (2011)
- O’Leary OF, "Faster, better, stronger : towards new antidepressant therapeutic strategies", Eur J Pharmacol, 753, pp.32~50 (2015)
- Wang SM, "Five potential therapeutic agents as antidepressants : a brief review and future directions", Expert Rev Neurother, 15, pp.1015~1029 (2015)
- Wang SM, "Criticisms of drugs in early development for the treatment of depression: what can be improved?", Expert Opin Investig Drugs, 24, pp.445~453 (2015)
- Zanos P, "Mechanisms of ketamine action as an antidepressant", Mol Psychiatry, 23, pp.801~811 (2018)
- Molero P, "Antidepressant efficacy and tolerability of ketamine and esketamine : a critical review", CNS Drugs, 32, pp.411~420 (2018)
- Kim J, "Esketamine for treatment-resistant depression-first FDA-approved antidepressant in a new class", N Engl J Med, 381, pp.1~4 (2019)
- Fu DJ, "Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients who have active suicidal ideation with intent : double-blind, randomized study(ASPIRE I)", J Clin Psychiatry, 81, pp.19~ (2020)
- Ionescu DF, "Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide ideation with intent : results of a phase 3, double-blind, randomized study(ASPIRE II)", Int J Neuropsychopharmacol, 24, pp.22~31 (2021)
- Canuso CM, "Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide : results of a double-blind, randomized, placebo-controlled study", Am J Psychiatry, 175, pp.620~630 (2018)
- "FDA approves a nasal spray to treat patients who are suicidal" (2020)[URL]
- Daly EJ, "Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression : a randomized clinical trial", JAMA Psychiatry, 75, pp.139~148 (2018)
- Popova V, "Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression : a randomized double-blind active-controlled study", Am J Psychiatry, 176, pp.428~438 (2019)
- Ochs-Ross R, "Efficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression-TRANSFORM-3", Am J Geriatr Psychiatry, 28, pp.121~141 (2020)
- Sheng Min Wang, "Agomelatine for the Treatment of Generalized Anxiety Disorder: A Meta-Analysis", Clinical Psychopharmacology and Neuroscience, 18(3), pp.423~433 (2020), 대한정신약물학회[DOI]
- Lyman GH, "The strengths and limitations of meta-analyses based on aggregate data", BMC Med Res Methodol, 5, pp.14~ (2005)
- Zheng W, "Adjunctive intranasal esketamine for major depressive disorder : a systematic review of randomized double-blind controlled-placebo studies-authors’ reply", J Affect Disord, 274, pp.955~ (2020)
- Papakostas GI, "Efficacy of esketamine augmentation in major depressive disorder : a meta-analysis", J Clin Psychiatry, 81, pp.19~ (2020)
- Higgins JP, "Cochrane Collaboration’s tool for assessing risk of bias in randomised trials", 343, pp.d5928~ (2011)
- Nakagawa S, "Meta-evaluation of meta-analysis : ten appraisal questions for biologists", BMC Biol, 15, pp.18~ (2017)
- Melsen WG, "The effects of clinical and statistical heterogeneity on the predictive values of results from meta-analyses", Clin Microbiol Infect, 20, pp.123~129 (2014)
- Fedgchin M, "Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression : results of a randomized, double-blind, activecontrolled study(TRANSFORM-1)", Int J Neuropsychopharmacol, 22, pp.616~630 (2019)
- "A study to evaluate the efficacy, safety and tolerability of fixed doses of intranasal esketamine in Japanese participants with treatment resistant depression" (2019)[URL]
- Faraone SV, "Interpreting estimates of treatment effects : implications for managed care", P T, 33, pp.700~711 (2008)
- "Anasthesiol Intensivmed Notfallmed Schmerzther", 1998, 764~770
- Pereira S, "Managing dissociative symptoms following the use of esketamine nasal spray : a case report", Int Clin Psychopharmacol, 36, pp.54~57 (2021)
- Doherty T, "Cardiac safety of esketamine nasal spray in treatment-resistant depression : results from the clinical development program", CNS Drugs, 34, pp.299~310 (2020)
- Wajs E, "Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression : assessment of long-term safety in a phase 3, open-label study(SUSTAIN-2)", J Clin Psychiatry, 81, pp.19~ (2020)