Hype or hope? High placebo response in major depression treatment with ketamine and esketamine: a systematic review and meta-analysis
BackgroundKetamine and esketamine offer a novel approach in the pharmacological treatment of major depressive disorder (MDD). This meta-analysis aimed to investigate the placebo response in double-blind, randomized controlled studies (RCTs) on patients with MDD receiving ketamine or esketamine.Metho...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2024.1346697/full |
| _version_ | 1797269070310014976 |
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| author | Alexandros Matsingos Marcel Wilhelm Laila Noor Cüneyt Yildiz Winfried Rief Stefan G. Hofmann Irina Falkenberg Tilo Kircher |
| author_facet | Alexandros Matsingos Marcel Wilhelm Laila Noor Cüneyt Yildiz Winfried Rief Stefan G. Hofmann Irina Falkenberg Tilo Kircher |
| author_sort | Alexandros Matsingos |
| collection | DOAJ |
| description | BackgroundKetamine and esketamine offer a novel approach in the pharmacological treatment of major depressive disorder (MDD). This meta-analysis aimed to investigate the placebo response in double-blind, randomized controlled studies (RCTs) on patients with MDD receiving ketamine or esketamine.MethodsFor this systematic review and meta-analysis Medline (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), PsycInfo and Embase databases were systematically searched for citations published up to March 17, 2023. A total number of 5017 abstracts was identified. Quality of the included trials was assessed with the Cochrane risk-of-bias tool. The meta-analysis was performed using a restricted maximum likelihood model. This study is registered with PROSPERO, number CRD42022377591.ResultsA total number of 14 studies and 1100 participants (593 in the medication group and 507 in the placebo group) meeting the inclusion criteria were selected. We estimated the pooled effect sizes of the overall placebo (dpl = -1.85 [CI 95%: -2.9 to -0.79] and overall treatment (dtr = -2.57; [CI 95% -3.36 to -1.78]) response. The overall placebo response accounts for up to 72% of the overall treatment response. Furthermore, we performed subgroup analysis of 8 studies for the for the 7 days post-intervention timepoint. Seven days post-intervention the placebo response (dpl 7d = -1.98 [CI 95%: -3.26 to -0.69]) accounts for 66% of the treatment response (dtr 7d = - 3.01 [CI 95%, -4.28 to -1.74]).ConclusionKetamine and esketamine show large antidepressant effects. However, our findings suggest that the placebo response plays a significant role in the antidepressant response and should be used for the benefit of the patients in clinical practice.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022377591. |
| first_indexed | 2024-04-25T01:42:32Z |
| format | Article |
| id | doaj.art-cda4083953ff467ea98cfed718064c0f |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-04-25T01:42:32Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-cda4083953ff467ea98cfed718064c0f2024-03-08T04:46:14ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402024-03-011510.3389/fpsyt.2024.13466971346697Hype or hope? High placebo response in major depression treatment with ketamine and esketamine: a systematic review and meta-analysisAlexandros Matsingos0Marcel Wilhelm1Laila Noor2Cüneyt Yildiz3Winfried Rief4Stefan G. Hofmann5Irina Falkenberg6Tilo Kircher7Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, GermanyDepartment of Clinical Psychology and Psychotherapy, Philipps-University Marburg, Marburg, GermanyDepartment of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, GermanyDepartment of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, GermanyDepartment of Clinical Psychology and Psychotherapy, Philipps-University Marburg, Marburg, GermanyTranslational Clinical Psychology, Department of Psychology, Philipps-University Marburg, Marburg, GermanyDepartment of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, GermanyDepartment of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, GermanyBackgroundKetamine and esketamine offer a novel approach in the pharmacological treatment of major depressive disorder (MDD). This meta-analysis aimed to investigate the placebo response in double-blind, randomized controlled studies (RCTs) on patients with MDD receiving ketamine or esketamine.MethodsFor this systematic review and meta-analysis Medline (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), PsycInfo and Embase databases were systematically searched for citations published up to March 17, 2023. A total number of 5017 abstracts was identified. Quality of the included trials was assessed with the Cochrane risk-of-bias tool. The meta-analysis was performed using a restricted maximum likelihood model. This study is registered with PROSPERO, number CRD42022377591.ResultsA total number of 14 studies and 1100 participants (593 in the medication group and 507 in the placebo group) meeting the inclusion criteria were selected. We estimated the pooled effect sizes of the overall placebo (dpl = -1.85 [CI 95%: -2.9 to -0.79] and overall treatment (dtr = -2.57; [CI 95% -3.36 to -1.78]) response. The overall placebo response accounts for up to 72% of the overall treatment response. Furthermore, we performed subgroup analysis of 8 studies for the for the 7 days post-intervention timepoint. Seven days post-intervention the placebo response (dpl 7d = -1.98 [CI 95%: -3.26 to -0.69]) accounts for 66% of the treatment response (dtr 7d = - 3.01 [CI 95%, -4.28 to -1.74]).ConclusionKetamine and esketamine show large antidepressant effects. However, our findings suggest that the placebo response plays a significant role in the antidepressant response and should be used for the benefit of the patients in clinical practice.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022377591.https://www.frontiersin.org/articles/10.3389/fpsyt.2024.1346697/fullketamineesketamineplaceboplacebo responsepsychoactive medicationdepression (MDD) |
| spellingShingle | Alexandros Matsingos Marcel Wilhelm Laila Noor Cüneyt Yildiz Winfried Rief Stefan G. Hofmann Irina Falkenberg Tilo Kircher Hype or hope? High placebo response in major depression treatment with ketamine and esketamine: a systematic review and meta-analysis Frontiers in Psychiatry ketamine esketamine placebo placebo response psychoactive medication depression (MDD) |
| title | Hype or hope? High placebo response in major depression treatment with ketamine and esketamine: a systematic review and meta-analysis |
| title_full | Hype or hope? High placebo response in major depression treatment with ketamine and esketamine: a systematic review and meta-analysis |
| title_fullStr | Hype or hope? High placebo response in major depression treatment with ketamine and esketamine: a systematic review and meta-analysis |
| title_full_unstemmed | Hype or hope? High placebo response in major depression treatment with ketamine and esketamine: a systematic review and meta-analysis |
| title_short | Hype or hope? High placebo response in major depression treatment with ketamine and esketamine: a systematic review and meta-analysis |
| title_sort | hype or hope high placebo response in major depression treatment with ketamine and esketamine a systematic review and meta analysis |
| topic | ketamine esketamine placebo placebo response psychoactive medication depression (MDD) |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2024.1346697/full |
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