SynthesisJournal of affective disorders2022
Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis.
Synthesis in Journal of affective disorders, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05814640 (Sequenced Treatment Alternatives to Relieve Adolescent Depression), which is not on this map. Cited by 95 papers, 7 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Sequenced Treatment Alternatives to Relieve Adolescent Depression (STAR-AD): a Pragmatic Clinical Trial
Who cites it
95 citing papers in PubMed, 7 syntheses or guidelines pooled it, 190 citations in OpenAlex.
- The effect of lithium on the structure and function of the human retina: a systematic review.BMC ophthalmology · 2026Pooled it
- Molecular and topographic mapping of antipsychotic effects: a meta-analysis of postsynaptic density proteins in animal models with translational implications.Molecular psychiatry · 2026Pooled it
- Rethinking Treatment-Resistant Depression: A Systematic Review of Novel Therapeutic Strategies and Precision Medicine Approaches.Actas espanolas de psiquiatria · 2025Pooled it
- Psychedelics and ketamine/esketamine in depressive disorders: biological mechanisms and associated neuroimaging and clinical changes.Translational psychiatry · 2025Pooled it
- Relative effectiveness of antidepressant treatments in treatment-resistant depression: a systematic review and network meta-analysis of randomized controlled trials.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Pooled it
- Effectiveness of pharmacological and non-pharmacological interventions for treatment-resistant depression in older patients: a systematic review and meta-analysis.BMJ mental health · 2025Pooled it
- Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: Réseau canadien pour les traitements de l'humeur et de l'anxiété (CANMAT) 2023 : Mise à jour des lignes directrices cliniques pour la prise en charge du trouble dépressif majeur chez les adultes.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2024Guideline
- The impact of levodopa on post-stroke depression: the ESTREL-depression-study.European stroke journal · 2026Trial
- Adjunctive brexpiprazole in patients with major depressive disorder who show minimal or partial response to antidepressant treatment: post hoc analysis of randomized controlled trials.The international journal of neuropsychopharmacology · 2025Trial
- Clinical and cost-effectiveness of lithium versus quetiapine augmentation for treatment-resistant depression in adults: LQD a pragmatic randomised controlled trial.Health technology assessment (Winchester, England) · 2025Trial
- Trial
- Adjunctive brexpiprazole 1 mg and 2 mg daily for Japanese patients with major depressive disorder following inadequate response to antidepressants: a phase 2/3, randomized, double-blind (BLESS) study.Psychiatry and clinical neurosciences · 2024Trial
- The Differential Relation of Emotional, Physical, and Sexual Abuse Histories to Antidepressant Treatment Remission and Persistence of Anhedonia in Major Depression: A CAN-BIND-1 Report.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2023Trial
- Treatment patterns and comparative clinical outcomes of ADHD medications in adolescents and young adults with comorbid major depressive disorder.Journal of affective disorders · 2026Article
- Treatment-Resistant Depression as a Heterogeneous Clinical Syndrome: A Personalized Medicine Framework for Diagnostic Reassessment, Suicide Risk, and Mechanism-Based Treatment.Journal of personalized medicine · 2026Review
- Efficacy and Safety of Lumateperone and Other Atypical Antipsychotics Approved as Adjunctive Treatment for Major Depressive Disorder in the United States: A Network Meta-Analysis.Advances in therapy · 2026Article
- Frequency of therapeutic drug monitoring in inpatient precision depression care and duration of hospitalization.Translational psychiatry · 2026Article
- Trends and patterns of medical stimulant use by US adults.Molecular psychiatry · 2026Article
- Revisiting the Management of Treatment-Resistant Depression.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2026Article
- Trials, trips, and tribulations: pathways for implementing psychedelic therapy in Ireland.The international journal of neuropsychopharmacology · 2026Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveTo compare the efficacy and discontinuation of augmentation agents in adult patients with treatment-resistant depression (TRD). We conducted a systematic review and network meta-analyses (NMA) to combine direct and indirect comparisons of augmentation agents.
methodsWe included randomized controlled trials comparing one active drug with another or with placebo following a treatment course up to 24 weeks. Nineteen agents were included: stimulants, atypical antipsychotics, thyroid hormones, antidepressants, and mood stabilizers. Data for response/remission and all-cause discontinuation rates were analyzed. We estimated effect-size by relative risk using pairwise and NMA with random-effects model.
resultsA total of 65 studies (N = 12,415) with 19 augmentation agents were included in the NMA. Our findings from the NMA for response rates, compared to placebo, were significant for: liothyronine, nortriptyline, aripiprazole, brexpiprazole, quetiapine, lithium, modafinil, olanzapine (fluoxetine), cariprazine, and lisdexamfetamine. For remission rates, compared to placebo, were significant for: thyroid hormone(T4), aripiprazole, brexpiprazole, risperidone, quetiapine, and olanzapine (fluoxetine). Compared to placebo, ziprasidone, mirtazapine, and cariprazine had statistically significant higher discontinuation rates. Overall, 24% studies were rated as having low risk of bias (RoB), 63% had moderate RoB and 13% had high RoB. LIMITATIONS: Heterogeneity in TRD definitions, variable trial duration and methodological clinical design of older studies and small number of trials per comparisons.
conclusionsThis NMA suggests a superiority of the regulatory approved adjunctive atypical antipsychotics, thyroid hormones, dopamine compounds (modafinil and lisdexamfetamine) and lithium. Acceptability was lower with ziprasidone, mirtazapine, and cariprazine. Further research and head-to-head studies should be considered to strengthen the best available options for TRD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.