The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
No benefit from flexible titration above minimum licensed dose in prescribing antidepressants for major depression: systematic review
Open accessAbstract
Background: In fixed‐dose antidepressant trials, the lower range of the licensed dose achieves the optimal balance between efficacy and tolerability. Whether flexible upward titration while side‐effects permit provides additional benefits is unknown. Methods: We did a systematic review of placebo‐controlled randomized trials that examined selective serotonin reuptake inhibitors (SSRIs), venlafaxine or mirtazapine in the acute treatment of major depression. Our primary outcome was response, defined as 50% or greater reduction in depression severity. Secondary outcomes included drop‐outs due to adverse effects and drop‐outs for any reason. We conducted random‐effects meta‐analyses to calculate the ratios of odds ratios (RORs) between trials comparing the flexible dose titrating above the minimum licensed dose against placebo and those comparing the fixed minimum licensed dose against placebo. Results: We included 123 published and unpublished randomized controlled trials (29 420 participants). There was no evidence supporting efficacy of the flexible dosing over the fixed low dose of SSRIs (ROR 0.96, 95% CI: 0.73 to 1.25), venlafaxine (1.24, 0.96 to 1.60) or mirtazapine (0.77, 0.33 to 1.78). No important differences were noted for tolerability or for any subgroup analyses except the superior efficacy of venlafaxine flexible dosing between 75 and 150 mg over the fixed 75 mg (1.30, 1.02 to 1.65). Conclusion: There was no evidence to support added value in terms of efficacy, tolerability or acceptability of flexibly titrating up the dosage over the minimum licensed dose of SSRIs or mirtazapine. For venlafaxine, increased efficacy can be expected by flexibly titrating up to 150 mg.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
A whole-of-society approach to the prevention of depression is justified.
“A whole-of-society approach to the prevention of depression is justified, linked to measures such as those implemented to curtail alcohol consumption and overlapping with successful actions by many countries to reduce the prevalence of coronary heart disease and several forms of cancer. 482”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [482]
There is limited benefit associated with increasing doses of SSRIs above the lower range of the licensed dose in general, whether using a fixed dosing regimen, a flexible dosing regimen, or as a second-step strategy in patients not responding to standard dosing.
“there is a limited benefit associated with increasing doses of SSRIs above the lower range of the licensed dose in general, whether using a fixed dosing regimen [4, 5], a flexible dosing regimen [46], or as a second-step strategy in patients not responding to standard dosing [6, 45].”
From The relationship between dose and serotonin transporter occupancy of antidepressants—a systematic review (2022) · cites this paper as [46]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., Leucht, S., Ruhe, H. G., Turner, E. H., Higgins, J. P. T., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(17)32802-7 · Cited by 3,541 · cited 5×
“There was no indication of small study effect or reporting bias in this dataset (6).”
InfluentialSelf-citationImputing missing standard deviations in meta-analyses can provide accurate results
Furukawa, T. A., Barbui, C., Cipriani, A., Brambilla, P., & Watanabe, N. (2006) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2005.06.006 · Cited by 1,568
Self-citationPRACTICE GUIDELINE FOR THE Treatment of Patients With Major Depressive Disorder
Gelenberg, A. J., Freeman, P. B., Markowitz, J. C., Rosenbaum, J. F., Thase, M. E., Trivedi, M. H., & Rhoads, R. S. (2010) · Cited by 1,372
Meyer, J. H., Wilson, A. A., Sagrati, S., Hussey, D., Carella, A., Potter, W. Z., Ginovart, N., Spencer, E. P., Cheok, A., & Houle, S. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.5.826 · Cited by 517 · cited 2×
“In our previous report, we suggested that these findings were consistent with the observation from PET studies that substantial (80%) blockade of the serotonin transporter occurs with minimum therapeutic doses of SSRIs and only small increases in occupancy become apparent with further dose escalation (20).”
ResultPapakostas, G. I., & D, M. F. M. (2008) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2008.08.009 · Cited by 381
Imputing response rates from means and standard deviations in meta-analyses
Furukawa, T. A., Cipriani, A., Barbui, C., Brambilla, P., & Watanabe, N. (2005) · International Clinical Psychopharmacology · doi:10.1097/00004850-200501000-00010 · Cited by 337
Self-citationUsers' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice
Warren, B. (2015) · Baylor University Medical Center Proceedings · doi:10.1080/08998280.2015.11929248 · Cited by 325
Furukawa, T. A., Cipriani, A., Cowen, P. J., Leucht, S., Egger, M., & Salanti, G. (2019) · The Lancet Psychiatry · doi:10.1016/s2215-0366(19)30217-2 · Cited by 322
Self-citationFurukawa, T. A., Cipriani, A., Atkinson, L. Z., Leucht, S., Ogawa, Y., Takeshima, N., Hayasaka, Y., Chaimani, A., & Salanti, G. (2016) · The Lancet Psychiatry · doi:10.1016/s2215-0366(16)30307-8 · Cited by 219
Self-citationFurukawa, T. A., Salanti, G., Atkinson, L. Z., Leucht, S., Ruhe, H. G., Turner, E. H., Chaimani, A., Ogawa, Y., Takeshima, N., Hayasaka, Y., et al. (2016) · BMJ Open · doi:10.1136/bmjopen-2015-010919 · Cited by 214
Self-citationKhin, N. A., Chen, Y., Yang, Y., Yang, P., & LAUGHREN, T. P. (2011) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.10m06191 · Cited by 211
Dechartres, A., Trinquart, L., Atal, I., Moher, D., Dickersin, K., Boutron, I., Perrodeau, E., Altman, D. G., & Ravaud, P. (2017) · BMJ · doi:10.1136/bmj.j2490 · Cited by 171 · cited 1×
“Moreover, the study year has been suggested to be a surrogate marker for study quality and other secular changes in the trial characteristics (28).”
BackgroundKhan, A., Khan, S., Walens, G., Kolts, R. L., & Giller, E. L. (2002) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300059 · Cited by 159
Differential physiological effects of a low dose and high doses of venlafaxine in major depression
Debonnel, G., Saint-André, É., Hébert, C., de Montigny, C., Lavoie, N., & Blier, P. (2006) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145705006413 · Cited by 148
Golden, R. N., Nemeroff, C. B., McSorley, P., Pitts, C. D., & Dube, E. M. (2002) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v63n0707 · Cited by 101
Ruhé, H. G., Booij, J., Weert, H. C. V., Reitsma, J. B., Fransen, E. J. F., Michel, M. C., & Schene, A. H. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2008.148 · Cited by 73
Ruhé, H. G., Huyser, J., Swinkels, J. A., & Schene, A. H. (2006) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.105.018325 · Cited by 69
for the SUN☺D Investigators, Kato, T., Furukawa, T. A., Mantani, A., Kurata, K., Hajime, K., Hirota, S., Sato, H., Sugishita, K., Chino, B., et al. (2018) · BMC Medicine · doi:10.1186/s12916-018-1096-5 · Cited by 60
Self-citationCurtis, H. J., & Goldacre, B. M. (2018) · BMJ Open · doi:10.1136/bmjopen-2017-019921 · Cited by 57
Does increasing dose improve efficacyin patients with poor antidepressantresponse: a review
Corruble, E., & Guelfi, J. (2000) · Acta Psychiatrica Scandinavica · doi:10.1034/j.1600-0447.2000.101005343.x · Cited by 38
Dold, M., Bartova, L., Rupprecht, R., & Kasper, S. (2017) · Psychotherapy and Psychosomatics · doi:10.1159/000477770 · Cited by 38
Rink, L., Braun, C., Bschor, T., Henssler, J., Franklin, J., & Baethge, C. (2018) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.17r11693 · Cited by 31
Missing outcome data in meta-analysis
Mavridis, D., Chaimani, A., Efthimiou, O., et al. (2014) · Evidence-Based Mental Health · doi:10.1136/eb-2014-101899 · Cited by 8
Which antidepressant doses are optimal?
Hieronymus, F. (2019) · The Lancet Psychiatry · doi:10.1016/s2215-0366(19)30221-4 · Cited by 8
Furukawa, T. A. (2014) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12278 · Cited by 7
Self-citationOptimal dosing of antidepressant drugs
Burchi, E., & D, M. F. M. (2019) · The Lancet Psychiatry · doi:10.1016/s2215-0366(19)30303-7 · Cited by 4
Flagged first, then by citations
Research works printed but not linked: 1
- NICE, 2009, Depression: the treatment and management of depression in adults (partial update of NICE clinical guideline 23)
Cited by
Sorted by citations
Time for united action on depression: a Lancet–World Psychiatric Association Commission
Herrman, H., Patel, V., Kieling, C., Berk, M., Buchweitz, C., Cuijpers, P., Furukawa, T. A., Kessler, R. C., Kohrt, B. A., Maj, M., et al. (2022) · The Lancet · doi:10.1016/s0140-6736(21)02141-3 · Cited by 1,104
Self-citationSforzini, L., Worrell, C., Kose, M., Anderson, I. M., Aouizerate, B., Arolt, V., Bauer, M., Baune, B. T., Blier, P., Cleare, A. J., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01381-x · Cited by 214
Self-citationSørensen, A., Ruhé, H. G., & Munkholm, K. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01285-w · Cited by 65
Furukawa, Y., Oguro, S., Obata, S., Hamza, T., Ostinelli, E. G., & Kasai, K. (2022) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13438 · Cited by 14
Metadata
- Authors
- Furukawa, T. A., Salanti, G., Cowen, P. J., Leucht, S., & Cipriani, A.
- Affiliations
- Kyoto University (JP)
- University of Bern (CH)
- Warneford Hospital (GB)
- Technical University of Munich (DE)
- Oxford Health NHS Foundation Trust (GB)
- Corresponding author
- Furukawa, T. A.
- Venue
- Acta Psychiatrica Scandinavica
- Publisher
- Wiley
- Published
- 2020-01-17
- Volume
- 141
- Issue
- 5
- Pages
- 401-409
- ISSN
- 0001-690X (ISSN-L)
- 1600-0447
- OpenAlex
- W2998616290
- Cited by
- 26
- References
- 26
- Citations by year
- 2025: 5 · 2024: 2 · 2023: 7 · 2022: 6 · 2021: 6
- FWCI
- 0.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Acta Psychiatrica Scandinavica (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion, other-oa)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Open Access CRIS of the University of Bern
- Funders
- Japan Society for the Promotion of Science London (17K19808)
- National Institute for Social Care and Health Research (BRC‐1215‐20005, RP‐2017‐08‐ST2‐006)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Mental Health Treatment and Access
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- antidepressants, major depressive disorder, selective serotonin reuptake inhibitors, venlafaxine, mirtazapine, acute treatment, treatment response, tolerability, adverse effects
- MeSH terms
- Venlafaxine Hydrochloride, Mirtazapine, Adult, Antidepressive Agents, Major Depressive Disorder, Depressive Disorder, Major, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Randomized Controlled Trials as Topic, Selective Serotonin Reuptake Inhibitors
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
