Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder

Dean, Rebecca; Hurducas, Cristina; Hawton, Keith; Spyridi, Styliani; Cowen, Philip J.; Hollingsworth, Sarah; Marquardt, Tahnee; Barnes, Annabelle; Smith, Rebecca P.; McShane, Rupert; Turner, Erick H.; Cipriani, Andrea

doi:10.1002/14651858.cd011612.pub3

Cited by 53 publications

(80 citation statements)

References 166 publications

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“…Studien wurden dabei anhand dreier aktueller systematischer Reviews ausgewählt. Der Review von Siegel et al beinhaltet RKS mit Patienten mit Suizidgedanken zu Studienbeginn [ 9 ], das Cochrane-Review von Dean et al Studien zu Depressionen [ 10 ] und schließlich der Review von Walsh et al zu Ketamin bei verschiedenen psychischen Störungen und Suizidalität [ 11 ]. Walsh et al geben einen systematischen Überblick zu anderen Reviews, darunter 6 Reviews zu Suizidalität, die wir ebenfalls berücksichtigen [ 5 , 12 – 16 ].…”

Section: Methodeunclassified

“…Der systematische Review mit Metaanalyse von Witt et al [14] berücksichtigte nur RKS und ist daher neben der Cochrane-Analyse von Dean [10] [14]. Ergänzt wurden die RKS von Ionescu et al [18] und Price et al [22].…”

Section: Ketaminunclassified

“…Einige Reviews sahen daher von einer metaanalytischen Synthese ab [ 9 , 11 , 15 , 16 ]. Bis auf die Cochrane-Analyse [ 10 ] kommen alle Reviews und die Metaanalyse von Witt et al [ 14 ] zu dem Schluss, dass Ketamin kurzfristig eine moderate bis starke Reduktion von Suizidgedanken bewirkt, jedoch nicht über den Zeitraum von einer halben bis einer Woche hinaus ( Abb. 1 ).…”

Section: Ergebnisseunclassified

“…Der systematische Review mit Metaanalyse von Witt et al [ 14 ] berücksichtigte nur RKS und ist daher neben der Cochrane-Analyse von Dean [ 10 ] die verlässlichste Arbeit. Basierend auf 15 Studien mit 572 Patienten schlussfolgern Witt et al, dass eine einmalige Infusion Ketamins möglicherweise eine Reduktion suizidaler Gedanken um bis zu 3 Tage bewirkt.…”

Section: Ergebnisseunclassified

“…Die Cochrane-Metaanalyse von Dean et al [ 10 ] hatte strengere Einschlusskriterien. Beide eingeschlossenen Placebo-RKS von Su et al [ 17 ] und Ionescu et al [ 18 ] fanden weder kurz- noch längerfristige, statistisch signifikante oder mittlere bis große Effekte für Ketamin, wobei die Patientenzahl mit insgesamt 68 klein war.…”

Section: Ergebnisseunclassified

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Suizidpräventive Effekte von Ketamin und Esketamin

Plöderl¹,

Hengartner²,

Volkmann³

2022

Nervenheilkunde

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ZUSAMMENFASSUNGKetamin und Esketamin werden als rasch und stark wirksame Mittel zur Reduktion von Depressivität und Suizidalität beschrieben. Dieser Beitrag gibt einen Überblick zur Wirksamkeit von Ketamin und Esketamin zur Reduktion von suizidalen Gedanken und Handlungen, basierend auf randomisierten kontrollierten Studien, die bis Dezember 2021 publiziert wurden. Für Ketamin gibt es Hinweise für eine beträchtliche Reduktion von Suizidgedanken, aber nur in den ersten 3 Tagen und die tatsächliche Effektstärke ist aufgrund der Schätzunsicherheit ungewiss. Für suizidale Handlungen fehlen zudem Daten. Die wenigen, aber qualitativ hochwertigeren Studien zu Esketamin fanden bestenfalls schwache Effekte bezüglich Suizidgedanken, auch unter Berücksichtigung der Schätzunsicherheit, und für suizidale Handlungen können keine gesicherten Aussagen getroffen werden. Das Nutzen-Schaden-Verhältnis von Ketamin und Esketamin in der Suizidprävention ist deshalb ungewiss.

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Section: Methodeunclassified

Section: Ketaminunclassified

Section: Ergebnisseunclassified

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Suizidpräventive Effekte von Ketamin und Esketamin

Plöderl¹,

Hengartner²,

Volkmann³

2022

Nervenheilkunde

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Management of Depression in Adults

Simon,

Moise,

Mohr

2024

JAMA

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ImportanceApproximately 9% of US adults experience major depression each year, with a lifetime prevalence of approximately 17% for men and 30% for women.ObservationsMajor depression is defined by depressed mood, loss of interest in activities, and associated psychological and somatic symptoms lasting at least 2 weeks. Evaluation should include structured assessment of severity as well as risk of self-harm, suspected bipolar disorder, psychotic symptoms, substance use, and co-occurring anxiety disorder. First-line treatments include specific psychotherapies and antidepressant medications. A network meta-analysis of randomized clinical trials reported cognitive therapy, behavioral activation, problem-solving therapy, interpersonal therapy, brief psychodynamic therapy, and mindfulness-based psychotherapy all had at least medium-sized effects in symptom improvement over usual care without psychotherapy (standardized mean difference [SMD] ranging from 0.50 [95% CI, 0.20-0.81] to 0.73 [95% CI, 0.52-0.95]). A network meta-analysis of randomized clinical trials reported 21 antidepressant medications all had small- to medium-sized effects in symptom improvement over placebo (SMD ranging from 0.23 [95% CI, 0.19-0.28] for fluoxetine to 0.48 [95% CI, 0.41-0.55] for amitriptyline). Psychotherapy combined with antidepressant medication may be preferred, especially for more severe or chronic depression. A network meta-analysis of randomized clinical trials reported greater symptom improvement with combined treatment than with psychotherapy alone (SMD, 0.30 [95% CI, 0.14-0.45]) or medication alone (SMD, 0.33 [95% CI, 0.20-0.47]). When initial antidepressant medication is not effective, second-line medication treatment includes changing antidepressant medication, adding a second antidepressant, or augmenting with a nonantidepressant medication, which have approximately equal likelihood of success based on a network meta-analysis. Collaborative care programs, including systematic follow-up and outcome assessment, improve treatment effectiveness, with 1 meta-analysis reporting significantly greater symptom improvement compared with usual care (SMD, 0.42 [95% CI, 0.23-0.61]).Conclusions and RelevanceEffective first-line depression treatments include specific forms of psychotherapy and more than 20 antidepressant medications. Close monitoring significantly improves the likelihood of treatment success.

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Esketamine vs Midazolam in Boosting the Efficacy of Oral Antidepressants for Major Depressive Disorder

Xiao

Jia

et al. 2023

JAMA Netw Open

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ImportanceLoss of a previously effective response while still using adequate antidepressant treatment occurs in a relatively high proportion of patients with major depressive disorder (MDD); therefore, there is a need to develop novel effective treatment strategies.ObjectiveTo assess the efficacy and safety of a single subanesthetic dose of esketamine in boosting the efficacy of oral antidepressants for treating fluctuating antidepressant response in MDD.Design, Setting, and ParticipantsThis single-center, double-blind, midazolam-controlled pilot randomized clinical trial was conducted at Beijing Anding Hospital, Capital Medical University in China. The study enrolled participants aged 18 years and older with fluctuating antidepressant response, defined as patients with MDD experiencing fluctuating symptoms after symptom relief and stabilization. Patient recruitment was conducted from August 2021 to January 2022, and participants were followed-up for 6 weeks. Data were analyzed as intention-to-treat from July to September 2022.InterventionsAll participants in the esketamine-treated group received intravenous esketamine at 0.2 mg/kg in 40 minutes. Participants in the midazolam control group received intravenous midazolam at 0.045 mg/kg in 40 minutes.Main Outcomes and MeasuresThe primary outcome was the response rate at 2 weeks, defined as a 50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary outcomes included response rate at 6 weeks, remission rates at 2 and 6 weeks, and change in MADRS and Clinical Global Impression–Severity score from baseline to 6 weeks; remission was defined by a MADRS score of 10 or lower.ResultsA total of 30 patients (median [IQR] age, 28.0 [24.0-40.0] years; 17 [56.7%] female) were randomized, including 15 patients randomized to midazolam and 15 patients randomized to esketamine; 29 patients completed the study. Response rates at 2 weeks were significantly higher in the esketamine-treated group than in the midazolam control group (10 patients [66.7%] vs 1 patient [6.7%]; P &lt; .001). Participants treated with esketamine experienced significantly greater reduction in MADRS score from baseline to 2 weeks compared with those treated with midazolam (mean [SD] reduction, 15.7 [1.5] vs 3.1 [1.3]; P &lt; .001). No serious adverse events were observed in this trial, and no psychotogenic effects and clinically significant manic symptoms were reported.Conclusions and RelevanceThis pilot randomized clinical trial found that a single subanesthetic dose of esketamine could boost the efficacy of oral antidepressants in treating fluctuating antidepressant response, with a good safety profile.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2100050335

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Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder

Cited by 53 publications

References 166 publications

Suizidpräventive Effekte von Ketamin und Esketamin

Suizidpräventive Effekte von Ketamin und Esketamin

Management of Depression in Adults

Esketamine vs Midazolam in Boosting the Efficacy of Oral Antidepressants for Major Depressive Disorder

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