Efficacy and safety of eight enhanced therapies for treatment-resistant depression: A systematic review and network meta-analysis of RCTs.
Qinghua Guo, Libo Guo, Yong Wang, Shaomei Shang
Psychiatry Research September 1, 2024 DOI: 10.1016/j.psychres.2024.116018 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Network meta-analysis Randomized Peer reviewed |
|---|---|
| Sample size | 12,105 |
| Population | Adults with treatment-resistant depression |
| Interventions | ECT Ketamine Esketamine Psilocybin Brexpiprazole Quetiapine |
| Topics | Depression |
| Keywords | Enhanced innovative therapies Network meta-analysis Treatment-resistant depression trd Refractory depression Psilocybin treatment Alternative depression treatments Drug trials |
| Citations | 19 |
| Key findings | ECT, ketamine, esketamine, and psilocybin are superior first-line treatments for TRD due to optimal balance of effectiveness and tolerability, while brexpiprazole and quetiapine showed no significant efficacy over placebo. |
Abstract
Treatment-Resistant Depression (TRD) challenges psychiatric treatment, with existing guidelines covering only a subset of augmentation strategies. A network meta-analysis following PRISMA guidelines examined the efficacy and safety of TRD treatments, analyzing 72 randomized controlled trials from eight databases, assessing response and remission rates, tolerability, and safety through the Cochrane Risk of Bias Tool and CINeMA framework. Including 12,105 participants, the analysis highlighted ECT, Ketamine, Esketamine, and Psilocybin as superior first-line treatments due to their optimal balance between effectiveness and tolerability. Brexpiprazole and Quetiapine showed no significant efficacy over placebo in response rates, while Esketamine and Psilocybin exhibited lower tolerability. The results advocate for ECT, Ketamine, Esketamine, and Psilocybin as preferred treatments for TRD, guiding clinical practice with evidence-based recommendations for enhancing treatment outcomes. This study underscores the importance of considering both efficacy and safety in selecting augmentation strategies for TRD.
Comparable studies
Other systematic reviews and meta-analyses on depression, most cited first.
Citations in the library
Cited by 9
- EEG vigilance and response to oral prolonged-release ketamine in treatment-resistant depression - A double-blind randomized validation study. Psychiatry Research Neuroimaging July 1, 2025
- A systematic review of psychedelic use and its relationship with meaning and purpose in life Journal of Psychedelic Studies April 25, 2025
- Regulatory Alignment of Psilocybin Clinical Trials in Major Depressive Disorder on ClinicalTrials.gov: A Cross-Sectional Analysis Pharmacopsychiatry April 17, 2025
- Investigating novel pharmacological strategies for treatment-resistant depression: focus on new mechanisms and approaches Expert Opinion on Drug Discovery January 31, 2025
- Improving access to novel treatments for treatment-resistant depression: The potential role of specialist clinics in Australia Australian & New Zealand Journal of Psychiatry May 26, 2026
and 4 more in the library
Cites 12
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
and 7 more in the library