SynthesisEuropean archives of psychiatry and clinical neuroscience2005
Is dose escalation of antidepressants a rational strategy after a medium-dose treatment has failed? A systematic review.
Synthesis in European archives of psychiatry and clinical neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 7 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 7 syntheses or guidelines pooled it, 175 citations in OpenAlex.
- [Second-step strategies in antidepressant pharmacotherapy : Results of current meta-analyses].Der Nervenarzt · 2025Pooled it
- Pharmacological Augmentation in Unipolar Depression: A Guide to the Guidelines.The international journal of neuropsychopharmacology · 2020Pooled it
- Predicting antidepressant response by monitoring early improvement of individual symptoms of depression: individual patient data meta-analysis.The British journal of psychiatry : the journal of mental science · 2019Pooled it
- Systematic Review and Meta-Analysis: Dose-Response Relationship of Selective Serotonin Reuptake Inhibitors in Major Depressive Disorder.The American journal of psychiatry · 2016Pooled it
- Combining Antidepressants in Acute Treatment of Depression: A Meta-Analysis of 38 Studies Including 4511 Patients.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2016Pooled it
- Evidence-based, pharmacological treatment guideline for depression in Korea, revised edition.Journal of Korean medical science · 2014Guideline
- Pooled it
- 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
- Population Pharmacokinetics of Viloxazine Extended-Release Capsules in Pediatric Subjects With Attention Deficit/Hyperactivity Disorder.Journal of clinical pharmacology · 2021Trial
- Pretreatment Reward Sensitivity and Frontostriatal Resting-State Functional Connectivity Are Associated With Response to Bupropion After Sertraline Nonresponse.Biological psychiatry · 2020Trial
- Trial
- Study protocol for a randomised pragmatic trial comparing the clinical and cost effectiveness of lithium and quetiapine augmentation in treatment resistant depression (the LQD study).BMC psychiatry · 2017Trial
- Strategic use of new generation antidepressants for depression: SUN(^_^)D study protocol.Trials · 2011Trial
- Trial
- Therapeutic drug monitoring in Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Adherence, acceptability and tolerability of venlafaxine extended release at dose of 300 mg/day in patients with major depressive disorder.Actas espanolas de psiquiatria · 2023Article
- Article
- Treatment resistance in psychiatry: state of the art and new directions.Molecular psychiatry · 2022Review
- Dose-response effects of selective serotonin reuptake inhibitor monotherapy for the treatment of depression: systematic review of reviews and meta-narrative synthesis.BMJ medicine · 2022Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMaximizing the dose of antidepressants is widely recommended in cases of non-response to medium-dose treatment. However, scientific evidence supporting high-dose treatment is scarce. Systematic studies comparing dose escalation with alternative strategies for refractory depression (i. e. augmentation or change of compound) are lacking. The aim of this publication is to review available direct and indirect evidence concerning dose increase of antidepressants after a medium-dose trial has failed.
methodWe performed a systematic literature search of Medline (1966-2003) and reviewed studies and publication references for available evidence. DATA SOURCES AND STUDY SELECTION: Studies of the following types were included: 1) dose increase studies in treatment refractory patients, 2) comparative dose studies, 3) therapeutic drug monitoring studies.
resultsAvailable data suggest differential efficacy of various pharmacological classes at more than medium-dosage. Direct evidence shows no increase of efficacy with high-dose selective serotonin reuptake inhibitor (SSRI) treatment; however, indirect evidence suggests enhanced therapeutic efficacy with high-dose tricyclic antidepressants. Few clinical data show ultra-high-dose treatment with the irreversible monoamine-oxidase-(MAO-) inhibitor tranylcypromine to be effective for refractory depression. Data concerning other selective compounds are insufficient to allow any definitive conclusion on the benefit of high-dose treatment.
conclusionsBased on available data highdose antidepressant treatment of patients refractory to medium-dose treatment is recommended for tricyclic compounds but not for SSRI. Some data suggest beneficial efficacy of ultra-high doses of the irreversible MAOI tranylcypromine. Research on other substance groups is limited and inconclusive. Prospective studies comparing dose escalation with alternative strategies for treatment of non-responding patients are needed.
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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.