Table 1 Overview of previous reviews summarising benefits and/or harms of duloxetine versus placebo in participants with MDD
First author (year of publication) | Title | Design | Published protocol | Sources of information | No of trials | No of participants | Assessment of bias in included trials | Conclusions: remission/response duloxetine versus placebo | Conclusions: adverse effects duloxetine versus placebo |
|---|---|---|---|---|---|---|---|---|---|
Krause et al. (2019) [29] | Efficacy and tolerability of pharmacological and non-pharmacological interventions in older patients with major depressive disorder: a systematic review, pairwise and network meta-analysis | Systematic review, pairwise and network meta-analysis | Yes | MEDLINE, Embase, PsycINFO, Cochrane Library, ClinicalTrials.gov, WHO registry, reference searches | 4 | 1347 | Yes | Superior: response defined as ≥ 50% reduction on HAM-D, MADRS, BDI or any other validated depression scale, score (1, 2) on CGI-improvement scale. Remission defined as ≤ 7 on HAM-D, ≤ 10 on MADRS, score (1,2) on CGI- severity scale, other criteria as defined in the primary trials. | Inferior: nausea, sedation, dizziness, diarrhea, hyperhidrosis, anticholinergic side effects, higher number of drop-outs due to adverse events. |
Sobieraj et al. (2019) [30] | Adverse effects of pharmacologic treatments of major depression in older adults | Systematic review and meta-analysis | Yes | MEDLINE, Embase, Cochrane Central, PsycINFO, ClinicalTrials.gov, International Controlled Trials Registry | 3 | 977 | Yes | Not assessed | Superior with exception of falls. Higher number of drop-outs due to adverse events. |
Cipriani et al. (2018) [24] | Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis | Systematic review and network meta-analysis | Yes | Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, AMED, UK National Research Register, ClinicalTrials.gov, websites of regulatory agencies, International Trial Registers | 23 | 6733 | Yes | Superior: response defined as ≥ 50% reduction of the total score on a standardised observer-rating scale for depression. Remission defined as ≤ 7 or 8 on HAM-D, ≤ 10 or 11 on MADRS or remission on any other standardised rating scale for depression. | Inferior: higher number of drop-outs due to adverse events. |
Tham et al. (2016) [31] | Efficacy and tolerability of antidepressants in people aged 65 years or older with major depressive disorder—a systematic review and a meta-analysis | Systematic review and meta-analysis | Yes | PubMed, Embase, Cochrane Library, CINAL, PsycINFO, Scopus | 3 | 977 | Yes | Superior: response defined as ≥ 50% post-treatment reduction of scores on HAM-D-17, -21, -24 or MADRS-interview based. Remission was defined depending upon the depression scale used. | Inferior: dry mouth, constipation, diarrhea, dizziness. |
Sharma et al. (2016) [32] | Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports | Systematic review and meta-analysis | No | European and UK drug regulators, Eli Lilly’s website | 12 | Not clear | No (tools not sufficient) | Not assessed | No evidence of increased risk in adults (questionable due to quality of available data). |
Thorlund et al. (2015) [33] | Comparative efficacy and safety of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in older adults: a network meta-analysis | Network meta-analysis | No | MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, Web of Science, ClinicalTrials.gov, conference proceedings of major psychiatric conferences for the past 2 years | 1 | 311 | No | Superior: partial response defined as 50% reduction on HAM-D or MADRS. | Inferior: dizziness. |
Casale et al. (2012) [34] | Duloxetine in the treatment of elderly people with major depressive disorder | Systematic review | No | MEDLINE, Embase, PsycLIT | 4 | 1132 | No | Superior: reduction in scores on depression scales used in primary trials such as HAM-D-17 and HAM-D-24. | Slightly inferior: dry mouth, diarrhea, nausea, fatigue, insomnia, decreased appetite and libido. |
Schueler et al. (2011) [35] | A systematic review of duloxetine and venlafaxine in major depression, including unpublished data | Meta-analysis | Yes | MEDLINE, Embase, PsycINFO, Psyndex, Cochrane Central Register of Controlled Trials, CDSR, DARE, Cochrane HTA, ClinicalTrials.gov, reference searches, unpublished data (Eli Lilly and Company) | 12 | 3069 | Yes | Superior: response and remission as defined in the primary trials. | Inferior: higher rate of discontinuation due to adverse events. |
Nelson JC. (2010) [36] | Anxiety does not predict response to duloxetine in major depression: results of a pooled analysis of individual patient data from 11 placebo-controlled trials | Pooled analysis of individual patient data | No | Eli Lilly and Company sponsored trials | 11 | 2841 | No | Superior: response defined as ≥ 50% improvement on HAM-D. Remission defined as endpoint HAM-D score ≤ 7. | Not assessed |
Mancini et al. (2010) [37] | Use of duloxetine in patients with an anxiety disorder or with comorbid anxiety and major depressive disorder: a review of the literature | Systematic review | No | MEDLINE, Embase | 16 | Not stated | No | Superior: HAM-D-17 total scores at end point, change in HAM-D. | Inferior: nausea, headache, dizziness, fatigue, suicidal thoughts, overdose. |
Gartlehner et al. (2009) [38] | The general and comparative efficacy and safety of duloxetine in major depressive disorder: a systematic review and meta-analysis | Systematic review and meta-analysis | No | MEDLINE, Embase, PsychLIT, Cochrane Library, International Pharmaceutical Abstracts | 11 | Not stated | Yes | Superior: remission defined as endpoint score of ≤ 7 on HAMD-17), could not perform meta-analysis due to insufficient data. | Lack of definite evidence but increased risk for adverse effects. |
Mukai et al. (2009) [39] | Treatment of depression in the elderly: a review of the recent literature on the efficacy of single- versus dual-action antidepressants | Systematic review | No | MEDLINE, PsycINFO, PubMed | 1 | 311 | No | Superior: change in HAM-D scores, GDS scores, cognitive score. | No difference in number of drop- outs. |
Frampton et al. (2007) [40] | Duloxetine: a review of its use in the treatment of major depressive disorder | Systematic review | No | MEDLINE, Embase, AdisBase | 8 | 1881 | No | Superior: response defined as 50% reduction from baseline in HAM-D-17 scores at last observation. Remission defined as endpoint HAM-D score ≤ 7. | Inferior: nausea, dry mouth, constipation, insomnia, dizziness, fatigue, somnolence, decreased appetite, sexual dysfunction. |
Mallinckrodt et al. (2006) [41] | Duloxetine for the treatment of major depressive disorder: a closer look at efficacy and safety data across the approved dose range | Pooled analyses | No | Eli Lilly and Company sponsored trials | 4 | 868 | No | Superior: mean change in HAM-D-17 total scores. Response defined as 50% reduction in HAM-D-17 total scores from baseline. Remission defined as HAM-D score ≤ 7. | Inferior: higher rate of discontinuation due to adverse events. |
Acharya et al. (2006) [42] | Duloxetine: meta-analyses of suicidal behaviors and ideation in clinical trials for major depressive disorder | Meta-analysis | No | Eli Lilly and Company, Shionogi Company Ltd | 12 | 2996 | No | Not assessed | No evidence of increased risk. |
Vis et al. (2005) [43] | Duloxetine and venlafaxine-XR in the treatment of major depressive disorder: a meta-analysis of randomized clinical trials | Meta-analysis | No | Cochrane, Embase, MEDLINE | 6 | 1481 | No | Superior: response defined as improvement of ≥ 50% from baseline on HAM-D or MADRS. Remission defined as HAM-D score ≤ 7 or MADRS ≤ 10. | Inferior: higher number of drop- outs due to adverse effects. |