Quantitative evaluation of multiple treatment regimens for treatment-resistant depression.
Yulin Feng, Yinghua Lv, Juan Yang, Ling Xu, Junchao Chen, Jihan Huang, Jiyuan Ren, Qingshan Zheng, Lujin Li
The International Journal of Neuropsychopharmacology February 4, 2025 DOI: 10.1093/ijnp/pyaf007 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review with meta-analysis and model-based meta-analysis Randomized Peer reviewed |
|---|---|
| Sample size | 3,059 |
| Population | Patients with treatment-resistant depression |
| Interventions | olanzapine with fluoxetine ayahuasca |
| Duration | 12 weeks |
| Topics | Depression |
| Keywords | Efficacy evaluation Modeling and simulation Treatment-resistant depression trd Refractory depression Combination therapy polypharmacy Multi-drug treatment Antidepressants psychotropic medications Psychiatric drugs Model-based meta-analysis mb |
| Citations | 3 |
| Key findings | Combination therapies outperform monotherapy for treatment-resistant depression, with olanzapine-fluoxetine and quetiapine-SSRI/SNRI combinations being most effective. |
Abstract
This study aims to quantitatively evaluate the efficacy and safety of various treatment regimens for treatment-resistant depression (TRD) across oral, intravenous, and intranasal routes to inform clinical guidelines. A systematic review identified randomized controlled trials on TRD, with efficacy measured by changes in the Montgomery-Åsberg Depression Rating Scale (MADRS). We developed pharmacodynamic and covariate models for different administration routes, using Monte Carlo simulations to estimate efficacy distribution. Dropout and adverse event-related dropout rates were analyzed via single-arm meta-analysis. Involving 22 studies with 56 treatment arms and 3059 patients, our findings suggest combination therapies outperform monotherapy, achieving an additional 6.5% reduction in MADRS scores over 12 weeks. The most effective combinations were olanzapine with fluoxetine and quetiapine with selective serotonin reuptake inhibitors/ selective serotonin and norepinephrine reuptake inhibitors. Injectable treatments, particularly ayahuasca, produced rapid effects, with a 77% reduction in MADRS scores at 15 days. Intranasal treatments reached efficacy sooner than oral ones, with 28-day efficacy similar to the 12-week efficacy of the olanzapine-fluoxetine combination. Dropout rates due to adverse events were similar across methods (4.5%-5.2%), but total dropouts were highest for oral (17.9%) and lowest for intranasal routes (10.6%). Additionally, there was considerable variation in the incidence of headache, dizziness, and nausea across different administration routes. The quantitative evaluation of 22 TRD treatments illuminates key pharmacodynamic parameters, bolstering the development of clinical guidelines and aiding the design of clinical trials and medical decision-making.
Comparable studies
Other systematic reviews and meta-analyses on depression, most cited first.
Citations in the library
Cites 16
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- 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 American Journal of Psychiatry May 21, 2019
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- 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, Active-Controlled Study (TRANSFORM-1) The International Journal of Neuropsychopharmacology July 9, 2019
- Double-Blind, Placebo-Controlled, Dose-Ranging Trial of Intravenous Ketamine as Adjunctive Therapy in Treatment-Resistant Depression (TRD) Molecular Psychiatry October 3, 2018
and 11 more in the library