Dose escalation of antidepressants in unipolar depression: a meta-analysis of double-blind, randomized controlled trials
Abstract
Background: As many patients with unipolar depression do not respond sufficiently to initial antidepressant monotherapy, a dose increase of the current administered antidepressant (dose escalation, high-dose treatment) is frequently carried out as next treatment measure. Methods: We conducted a meta-analysis which included all double-blind randomized controlled trials (RCTs) comparing a dose increase of antidepressants directly to continuation of standard-dose treatment in unipolar depressive patients who were non- responders to standard-dose pharmacotherapy. A mean change in the Hamilton Rating Scale for Depression (HAM-D) total score was the primary outcome. Secondary outcomes were response rates and discontinuation rates due to any reason, inefficacy, and adverse effects. Hedges g and risk ratios were calculated as effect sizes. Results: Seven double-blind RCTs (8 study arms) representing 1,208 participants were included. Fluoxetine (N [number of studies] = 2, n [number of patients] = 448), sertraline (N = 2, n = 272), paroxetine (N = 2, n = 146), duloxetine (N = 1, n = 255), and maprotiline (N = 1, n = 87) were investigated. Dose escalation was not more efficacious in HAM-D total score reduction than maintaining standard-dose treatment, neither for the pooled antidepressant group (N = 7, n = 999; Hedges g = -0.04, 95% CI: -0.20 to 0.12; p = 0.63) nor the individual antidepressants. No differences could be determined for response rates, all-cause discontinuation, and drop-outs due to inefficacy. Significantly more patients in the dose escalation group dropped out due to adverse effects than in the standard-dose continuation group. The metaregressions indicate no influence of baseline symptom severity or amounts of dose increments on effect sizes. Conclusions: According to our meta-analytic findings, dose escalation after initial non-response to standard-dose pharmacotherapy cannot be regarded as general evidence-based treatment option in unipolar depression.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Individuals with depression seem to benefit more when there is at least a modicum of human interaction, especially in more severe depression.
“However, individuals with depression seem to benefit more when there is at least a modicum of human interaction, especially in more severe depression. 503”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [503]
A recent meta-analysis found no significant efficacy difference between tricyclics and SSRIs for the average patient.
“a recent metaanalysis of trials comparing tricyclics to selective serotonin reuptake inhibitors failed to show any significant difference in efficacy for the average patient [8].”
From The Deceptive Manifestations of Treatment Resistance in Depression: A New Look at the Problem (2020) · cites this paper as [8]
The citation lists haven’t been fetched yet
References 36 · Cited by 38
- Authors
- Dold, M., Bartova, L., Rupprecht, R., & Kasper, S.
- Affiliations
- Medical University of Vienna (AT)
- University Hospital Regensburg (DE)
- Venue
- Psychotherapy and Psychosomatics
- Publisher
- S. Karger AG
- Published
- 2017
- Volume
- 86
- Issue
- 5
- Pages
- 283-291
- ISSN
- 0033-3190 (ISSN-L)
- 1423-0348
- OpenAlex
- W2755184922
- Cited by
- 38
- References
- 36
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 7 · 2020: 7 · 2019: 6 · 2018: 6 · 2017: 1
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychotherapy and Psychosomatics (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Keywords
- major depressive disorder, antidepressant non-response, fluoxetine, sertraline, paroxetine, duloxetine, maprotiline, treatment response, treatment discontinuation, adverse effects, baseline symptom severity
- MeSH terms
- Antidepressive Agents, Major Depressive Disorder, Depressive Disorder, Major, Double-Blind Method, Drug Administration Schedule, Female, Fluoxetine, Humans, Male, Randomized Controlled Trials as Topic, Treatment Outcome, Selective Serotonin Reuptake Inhibitors, Paroxetine, Sertraline
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
