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Cited by 65Treatment of Major DepressionMental Health Treatment and AccessAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

Efficacy and tolerability of pharmacological and non-pharmacological interventions in older patients with major depressive disorder: A systematic review, pairwise and network meta-analysis

Open access
Krause, Marc, Gutsmiedl, Katharina, Bighelli, Irene, Schneider-Thoma, Johannes, Chaimani, Anna, Leucht, Stefan·2019·European Neuropsychopharmacology
DOI 10.1016/j.euroneuro.2019.07.130
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Abstract

As there is currently no comprehensive evaluation about the efficacy and safety of interventions in elderly patients with major depressive disorder, we did a systematic review and network meta-analysis about all interventions in this population. We searched the specialised register of the Cochrane common mental disorders group, MEDLINE, EMBASE, PsycINFO, CochraneLibrary, ClinicalTrials.gov and the WHO registry until Dec 12, 2017 to identify all randomized controlled trials about the treatment of major depressive disorder in patients over an age of 65. The primary outcome was response defined as reduction of at least 50% on the Hamilton Depression Scale or any other validated depression scale. Secondary outcomes were remission, depressive symptoms, dropouts total, dropouts owing to inefficacy and dropouts due to adverse events, quality of life and social functioning. Additionally, we analysed 116 adverse events. We identified 129 references from 53 RCTs with 9274 participants published from 1990 to 2017. The mean participant age was 73.7 years. In terms of the primary outcome response to treatment the network-meta-analysis showed significant superiority compared to placebo for quetiapine and duloxetine; in addition, agomelatine, imipramine and vortioxetine outperformed placebo in pairwise meta-analyses, and there were also significant superiorities of several antidepressants compared to placebo in secondary efficacy outcomes. Very limited evidence suggests that competitive memory training, geriatric home treatment group and detached mindfulness condition reduce depressive symptoms. Several antidepressants and quetiapine have been shown to be efficacious in elderly patients with major depressive disorder, but due to the comparably few available data, the results are not robust. Differences in the multiple side-effects analysed should also be considered in drug choice. Although there were significant effects for some non-pharmacological treatments, the overall evidence for non-pharmacological treatments in major depressive disorder is insufficient, because it is based on a few trials with usually small sample sizes.

Verified 2026-10-06 · 9 references not checked yet

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and network meta-analysis evaluated all pharmacological and non-pharmacological interventions for acute major depressive disorder in patients aged ≥65 years, including 53 RCTs with 9274 participants. Quetiapine and duloxetine showed the most consistent efficacy signals versus placebo, but evidence was limited by inconsistency, imprecision, and sparse non-pharmacological data.

Key findings

  • For response, quetiapine and duloxetine were significantly superior to placebo in network meta-analysis (mean RR 2.09 and 1.83); in pairwise meta-analysis, agomelatine, duloxetine, imipramine, quetiapine, and vortioxetine also outperformed placebo (RRs 1.53, 1.81, 1.71, 2.09, 1.49).
  • For remission, quetiapine, mirtazapine, and duloxetine were significantly better than placebo (mean RRs 2.38, 1.90, 1.52); for depressive symptoms, only escitalopram was significant in network meta-analysis (mean SMD −0.81), while pairwise analyses found agomelatine, duloxetine, escitalopram, imipramine, quetiapine, tianeptine, and vortioxetine superior to placebo (SMDs −0.36, −0.38, −1.08, −0.52, −0.88, −0.54, −0.36).
  • Tolerability varied: fluoxetine and amitriptyline had more total dropouts than placebo (RRs 1.49 and 1.81), and many drugs caused more dropouts due to adverse events; quetiapine was associated with better quality of life versus placebo (SMD 0.47), but also more sedation and anticholinergic effects.
  • Non-pharmacological evidence was sparse: only five of eight included studies provided usable data, with single-study signals for detached mindfulness, competitive memory training, geriatric home treatment, and collaborative care, but no meta-analysis was possible.

Methods

  • Systematic review and random-effects pairwise and network meta-analysis of RCTs in patients aged ≥65 years with operationalised acute MDD, minimum 4 weeks’ treatment, drugs as monotherapy; searches ran to Dec 12, 2017.
  • Included 53 RCTs (46 with usable outcome data) and 9274 participants; mean age 73.7 years (range 68.9–83.2), mean trial duration 9 weeks; antidepressants were studied in 44 of 53 trials, non-pharmacological interventions in 8, and quetiapine in 1 placebo-controlled trial.
  • Primary outcome was response (≥50% reduction on validated depression scale or CGI-I 1–2); secondary outcomes included remission, depressive symptoms, dropouts, quality of life, social functioning, and adverse events; analyses used Stata 14, SUCRA rankings, inconsistency tests, CINeMA, and planned meta-regressions.

Limitations

  • The paper states that evidence was limited for some comparisons, especially non-pharmacological treatments; pharmacological and non-pharmacological treatments could not be connected in one network meta-analysis; reporting was often insufficient, and more than 50% of included studies lacked details on randomisation and allocation concealment.
  • The paper reports significant overall inconsistency for response (χ² 32.96, p=0.0003) and depressive symptoms (χ² 61.02, p=0.0000), and notes that transitivity could not be well explored because few studies were available per comparison; CINeMA confidence was mainly moderate to very low.
  • The paper states that publication bias could not be formally tested, that exclusion of pre-1990 studies lost some older-drug trials, and that quetiapine monotherapy for unipolar MDD is off-label; it also notes that meta-analysis can generate hypotheses but cannot empirically test them.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.euroneuro.2019.07.130

Cites

97 of 106 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 34 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Imipramine was associated with significantly fewer patients with dyspeptic signs compared to placebo, fluoxetine and citalopram.

    “Imipramine was associated with significantly fewer patients with dyspeptic signs compared to placebo Fig 4 i, fluoxetine and citalopram (RRs 0.39, 0.24, 0.12) (eTab13).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Duloxetine showed significantly higher response rates compared to placebo (mean RR 1.83).

    “Quetiapine and duloxetine showed significantly higher response rates compared to placebo (mean RR 2.09 and RR 1.83).”
    Quote in the paperSubstantial claim
  • Findingown data

    Escitalopram and vortioxetine were better (fewer anticholinergic side-effects) compared to all interventions mentioned at the beginning of the section, with the exception of dothiepine.

    “Escitalopram and vortioxetine were better compared to all interventions mentioned at the beginning of this section, with the exception of dothiepine.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Quetiapine, dothiepin, duloxetine, reboxetine, mirtazapine, amitriptyline and imipramine were associated with more anticholinergic side-effects compared to placebo.

    “Quetiapine, dothiepin, duloxetine, reboxetine, mirtazapine, amitriptyline and imipramine associated with more anticholinergic side-effects compared to placebo (mean RRs 1.96, 2.63, 3.02, 3.36, 3.56, 3.65, 3.87) Fig. 4 a and compared with tianeptine, citalopram and fluoxetine.”
    Quote in the paperSubstantial claim
  • Findingown data

    Maprotiline and mianserin were associated with significantly less insomnia compared to citalopram, imipramine, bupropion, escitalopram, venlafaxine and fluoxetine.

    “Maprotiline and mianserin were associated with significantly less insomnia compared to citalopram, imipramine, bupropion, escitalopram, venlafaxine and fluoxetine (mean RRs 0.32, 0.14, 0.13, 0.12, 0.12, 0.12 and 0,37, 0.16, 0.15, 0.14, 0.14, 0.13) (eTab15).”
    Quote in the paperSubstantial claim
  • May combine two claims. 23
  • Classified as probably not a substantial claim. 24

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    Findingown data

    Milnacipran and imipramine were associated with significantly fewer patients with diarrhoea than placebo, and duloxetine was associated with more patients with diarrhoea compared to placebo.

    “Milnacipran and imipramine were associated with significantly fewer patients with diarrhoea than placebo (mean RRs 0.02, 0.05) Fig. 4 j, and duloxetine was associated with more patients with diarrhoea compared to placebo (RR 2.31).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Duloxetine, venlafaxine and imipramine were associated with significantly more dizziness compared to placebo, and tianeptine was associated with fewer events compared to placebo.

    “Duloxetine, venlafaxine and imipramine were associated with significantly more dizziness compared to placebo (mean RRs 1.81, 2.69 and 2.86) Fig. 4 f, and tianeptine was associated with fewer events compared to placebo (RR 0.27).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    When a fixed effects model was used more drugs were significantly superior to placebo, but this model is not appropriate in the presence of inconsistency.

    “When a fixed effects model was used more drugs were significantly superior to placebo, but this model is not appropriate in the presence of inconsistency.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The mean age in our studies was 73.7 years with a range of 68.9-83.2.

    “the mean age in our studies was 73.7 years with a range of 68.9-83.2.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

    Findingnone given

    There were no significant differences between any intervention and placebo for tremor.

    “There were no significant differences between any intervention and placebo.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Venlafaxine produced more anticholinergic side effects than nortriptyline, while nortriptyline was associated with more dizziness than venlafaxine.

    “Venlafaxine produced more anticholinergic side effects than nortriptyline (RR 3.29), while nortriptyline was associated with more dizziness than venlafaxine (RR 2.25) ( Anon, 2003) .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Anon, 2003

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  • May combine two claims.

    Findingcitation

    In the study by Ekkers et al., competitive memory training was associated with significantly higher reduction of depressive symptoms compared to treatment as usual, and TAU was associated with significantly more dropouts compared to CMT.

    “In a study of 7 weeks duration ( n = 93) by Ekkers et al. (2011) , competitive memory training (CMTn = 53) was associated with significantly higher reduction of depressive symptoms compared to treatment as usual (TAU, n = 40) (SMD -0.53).TAU was associated with significantly more dropouts compared to CMT (RR 6.63).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ekkers et al. (2011) source

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    Findingcitation

    In long-term studies, duloxetine was superior to placebo concerning depressive symptoms and dropouts due inefficacy, but produced more dropouts due to adverse events and anticholinergic side-effects than placebo.

    “The only statistically significant results were that duloxetine was superior to placebo concerning depressive symptoms (mean SMD -0.39) and dropouts due inefficacy, but it produced more dropouts due to adverse events and anticholinergic side-effects than placebo ( EUCTR2008-001829-33-FR, 2008) .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites EUCTR2008-001829-33-FR, 2008

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  • May combine two claims.

    Findingown data

    The assessments of confidence in the estimates using CINeMA was mainly moderate to very low, primarily due to study limitations and imprecision, and due to inconsistency of the primary outcome.

    “The assessments of confidence in the estimates using CINeMA was mainly moderate to very low, primarily due to study limitations (high risk of bias) and imprecision (eAppendix16), and due to the above described inconsistency of the primary outcome.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    In the study by Klug et al., geriatric home treatment group was associated with significantly higher reduction of depressive symptoms compared to TAU in the short term and long term, and improved quality of life and social functioning more than TAU.

    “In the study by ( Klug et al., 2010) ( n = 60), geriatric home treatment group (GHTG, n = 30) was associated with significantly higher reduction of depressive symptoms compared to treatment as usual (TAU, n = 30) (SMDs -1.05) in the short term (12 weeks).Furthermore GHTG improved quality of life and social functioning significantly more than TAU (SMDs -1.13 and -0.93).In the long term (52 weeks) G”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Klug et al., 2010

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    Findingcitation

    In the 4-week study by Ahmadpanah et al., detached mindfulness condition showed a significantly higher remission rate and a significantly higher reduction of depressive symptoms compared to the control group.

    “In the 4-week study by Ahmadpanah et al. (2017) , detached mindfulness condition (DMC, n = 19) showed a significantly higher remission rate (mean RR 18.90) and a significantly higher reduction of depressive symptoms (mean SMD -1.69) compared to the control group (leisure activities, n = 17).”
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    • cites Ahmadpanah et al. (2017)

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    Findingown data

    There was no significant overall inconsistency for other efficacy outcomes, and for side-effects except headaches.

    “For other efficacy outcomes no significant overall inconsistency was identified.There was also no significant overall inconsistency for side-effects, except for headaches (chi ²: 12.62, p: 0.0272).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In the study by Bosanquet et al., in the long-term Collaborative Care was associated with a significantly higher reduction of depressive symptoms and fewer total dropouts compared to TAU.

    “In the study by Bosanquet et al. (2017) ( n = 485) no shortterm data was reported.In the long-term Collaborative Care (CC, n = 249) was associated with a significantly higher reduction of depressive symptoms (SMD -0.35), and fewer total dropouts (RR 0.10) compared to treatment as usual (TAU, n = 236).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bosanquet et al. (2017)

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  • May combine two claims.

    Findingown data

    Although in network meta-analysis not all results were statistically significant, the direction of the effect was the same as that in pairwise meta-analysis, making the results complementary.

    “although in network meta-analysis not all results were statistically significant, the direction of the effect was the same as that in pairwise meta-analysis, making the results complementary.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    Evidence for non-pharmacological treatments as well as the evidence for most of the antidepressants is still scarce.

    “we showed that the evidence for non-pharmacological treatments as well as the evidence for most of the antidepressants is still scarce”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    We included 53 studies with 9274 participants.

    “Although we included 53 studies with 9274 participants”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Findingown data

    Our review provides a comprehensive evaluation of efficacy and 116 adverse events.

    “our review provides a comprehensive evaluation of efficacy and hundred-sixteen adverse events”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingreasoning

    This approach led to network meta-analyses for 22, and pairwise meta-analyses for 116 adverse events.

    “This approach led to network meta-analyses for 22, and pairwise meta-analyses for 116 adverse events.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    We lost a few studies on older drugs due to the exclusion of studies about pharmacological interventions published before 1990.

    “we lost a few studies on older drugs due to the exclusion of studies about pharmacological interventions published before 1990.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    We found high statistical inconsistency in the primary outcome 'response to treatment', and depressive symptoms and headache.

    “we found high statistical inconsistency in the primary outcome 'response to treatment', and depressive symptoms and headache.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    An a priori written study protocol was registered at PROSPERO (CRD42018107814).

    “An a priori written study protocol was registered at PROSPERO: CRD42018107814 ( Krause et al., 2018) (eAppendix 1).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Krause et al., 2018

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  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Studies that demonstrated a high risk of bias for sequence generation or allocation concealment were excluded.

    “Furthermore, studies that demonstrated a high risk of bias for sequence generation or allocation concealment were excluded ( Higgins JPT, 2011) .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Higgins JPT, 2011

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Confidence in estimates of the primary outcome was assessed with CINeMA.

    “Additionally, we assessed the confidence in estimates of the primary outcome with Confidence in Network Meta-Analysis (CINeMA) ( CINeMA, 2017;Salanti et al., 2014 ), an adaptation of the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE) specifically developed for network meta-analysis ( Salanti et al., 2014) .”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites CINeMA, 2017

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    • cites Salanti et al., 2014 source

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  • May combine two claims.

    Interpretationcitation

    Very limited evidence suggests that competitive memory training, geriatric home treatment group and detached mindfulness condition reduce depressive symptoms in the short term, and collaborative care in the long-term.

    “Very limited evidence suggests that competitive memory training, geriatric home treatment group and detached mindfulness condition reduce depressive symptoms in the short term, and collaborative care in the long-term.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    We a priori decided in our protocol to only include studies published since 1990.

    “we a priori decided in our protocol to only include studies published since 1990.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In contrast to our NMA, efficacy differences between antidepressants had not been detected in older adults.

    “In contrast to our NMA, efficacy differences between antidepressants had not been detected in older adults ( Gerson et al., 1999;Mittmann et al., 1997;Williams, 2000 )”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Gerson et al., 1999

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    • cites Mittmann et al., 1997

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    • cites Williams, 2000

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    Study design and conductcitation

    Statistical inconsistency was tested with three different approaches: loop-specific, side-splitting, and design-by-treatment interaction model.

    “Statistical inconsistency was tested with three different approaches: the loop-specific approach that tests inconsistency in every closed loop of evidence ( Bucher et al., 1997) ; the sidesplitting method that tests for each comparison's discrepancies between direct and indirect evidence obtained by the entire network ( Dias et al., 2010) ; and the design-by-treatment interaction model that tests”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Bucher et al., 1997 source

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    • cites Dias et al., 2010 source

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    Premisecitation

    In previous reviews cognitive behavioral therapy was more efficacious than passive control interventions.

    “In previous reviews cognitive behavioral therapy was more efficacious than passive control interventions ( Kiosses et al., 2011;Peng et al., 2009;Wilson et al., 2008 )”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Kiosses et al., 2011 source

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    • cites Peng et al., 2009

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    • cites Wilson et al., 2008

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    Premisecitation

    Several meta-analyses showed a significantly greater efficacy of various antidepressants compared to placebo in older adults, although effect sizes varied.

    “several meta-analyses showed a significantly greater efficacy of various antidepressants compared to placebo in older adults, although the effect sizes varied ( Kok et al., 2012;Mottram et al., 2006;Thorlund et al., 2015;Wilson et al., 2001 )”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Kok et al., 2012 source

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    • cites Mottram et al., 2006

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    • cites Thorlund et al., 2015 source

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    Study design and conductcitation

    We focused on an age group which would be classified as geriatric by recent definitions, including mainly an age of over 70.

    “we therefore focused on an age group which would be classified as geriatric by recent definitions ( Sieber, 2007) including mainly an age of over 70.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Sieber, 2007

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  • Classified as probably not a substantial claim.

    Study design and conductown data

    Study selection and data extraction were performed independently by at least 2 reviewers.

    “Study selection and data extraction were performed independently by at least 2 reviewers (MK, KG).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Potential small-trial effects and publication bias were assessed using funnel plots.

    “We assessed potential small-trial effects and publication bias, using simple funnel-plots for pairwise meta-analyses and comparison-adjusted funnel plots for network-meta-analysis, if at least 10 and 3 trials per comparison were available respectively ( Chaimani et al., 2013) .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Chaimani et al., 2013 source

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    Study design and conductcitation

    Study quality was independently assessed by at least 2 reviewers using the Cochrane Collaboration's risk-of-bias tool.

    “Study quality was independently assessed by at least 2 reviewers (MK, KG) using the Cochrane Collaboration's risk-of-bias tool ( Higgins JPT, 2011) .”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Higgins JPT, 2011

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    Premisecitation

    TCA were associated with more dropouts in a Cochrane review from 2006.

    “TCA were associated with more dropouts in a Cochrane review from 2006 ( Mottram et al., 2006)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Mottram et al., 2006

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  • May combine two claims.

    Premisecitation

    Furukawa et al. (2016) have shown that placebo response was lower in antidepressant before 1990, while placebo response remained stable in the subsequent 30 years.

    “The main reason was that ( Furukawa et al., 2016) have shown that placebo response was lower in antidepressant before 1990, while placeboresponse remained stable in the subsequent 30 years.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Furukawa et al., 2016 source

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    Premisecitation

    All antidepressants examined by Cipriani et al. (2018) were more efficacious than placebo.

    “In contrast to our report all antidepressants examined by Cipriani et al. (2018 ) were more efficacious than placebo.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cipriani et al., 2018 source

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  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    We applied specific inclusion criteria suitable for an appropriate definition of the target population.

    “We applied specific inclusion criteria suitable for an appropriate definition of the target population, which is particularly important when conducting a network metaanalysis.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    We downgraded the strength of the evidence in the CINeMA.

    “we downgraded the strength of the evidence in the CINeMA”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    To use quetiapine in monotherapy for major depressive disorder means off-label use.

    “To use it in monotherapy for major depressive disorder means off-label use.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Quetiapine is only approved as a monotherapy in depression in the context of bipolar disorder, while in unipolar depression it is only approved as an augmentation strategy.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    It is known that publication bias exists in this area.

    “it is known that publication bias exists in this area ( Turner et al., 2008)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Turner et al., 2008 source

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  • May combine two claims.

    Study design and conductreasoning

    The trials appeared to be similar and thus transitive.

    “the trials appeared to be similar and thus transitive.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    We could not formally test for publication bias.

    “we could not formally test for publication bias”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    We undertook a comprehensive literature search.

    “We undertook a comprehensive literature search”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    We obtained some unpublished data from authors of included studies.

    “We obtained some unpublished data from authors of included studies.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    We extracted all side-effects reported in the primary studies and built groups of similar side effects according to an adapted MedDRA approach.

    “We extracted all side-effects reported in the primary studies and built groups of similar side effects according to an adapted MedDRA”
    Quote in the paperSubstantial claim
45 of 45

  • The authors state this as an assumption.

    A common heterogeneity value is assumed across all comparisons.

    “We assumed a common heterogeneity value across all comparisons.”

  • The authors state this as an assumption.

    The transitivity assumption holds: studies comparing different sets of interventions are sufficiently similar to provide valid indirect inferences.

    “This assumption implies that studies comparing different sets of interventions are sufficiently similar to provide valid indirect inferences, which we tried to ensure by applying narrow inclusion criteria and making populations similar within and across treatment comparisons.”

  • The authors state this as an assumption.

    If a trial was described as double-blind but randomization was not explicitly mentioned, study participants were randomized.

    “If a trial was described as double-blind but randomization was not explicitly mentioned, we assumed that study participants were randomized.”

  • The paper relies on this without support.

    In many countries the age of 65 is associated with marked changes in life such as retirement or a loss of close relatives.

    “In many countries the age of 65 is associated with marked changes in life such as retirement or a loss of close relatives.”

  • The paper relies on this without support.

    Nowadays the physical health of patients in their late 50s or early 60s does often not differ from general adults.

    “nowadays the physical health of patients in their late 50 s or early 60 s does often not differ from general adults.”

  • The paper relies on this without support.

    Depressive symptoms can be very different between different types of depression, which may lead to differences in treatment effects.

    “as depressive symptoms can be very different between different types of depression which may lead to differences in treatment effects”

  • The authors state this as an assumption.

    The population of included studies could a priori be assumed to be quite homogeneous.

    “Due to these strict inclusion criteria, the population of included studies could a priori be assumed to be quite homogeneous”

  • The paper relies on this without support.

    Older antidepressants such as TCAs are nowadays not commonly used in clinical practice.

    “these drugs are nowadays not commonly used in clinical practice.”

  • The paper relies on this without support.

    Quetiapine is only approved as a monotherapy in depression in the context of bipolar disorder, while in unipolar depression it is only approved as an augmentation strategy.

    “quetiapine is only approved as a monotherapy in depression in the context of bipolar disorder, while in unipolar depression it is only approved as an augmentation strategy.”

  • The paper relies on this without support.

    Older patients clearly different from general adults are usually excluded from studies in the general population.

    “While such patients are usually excluded from studies in the general population”

  • The paper relies on this without support.

    Previous reviews incompletely addressed side-effects, quality of life, functioning and other outcomes compared to our comprehensive assessment.

    “Compared to our comprehensive assessment of outcomes, side-effects, quality of life, functioning and other outcomes were incompletely addressed by previous reviews”

  • The paper relies on this without support.

    The older studies are the more they may also differ in other methodological and patient characteristics.

    “The older studies are the more they may also differ in other methodological and patient characteristics.”
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Cites

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4 of the 110 references couldn’t be matched to a known paper.

Research works printed but not linked: 4

  1. Azar, 2010, Remission from major depression in a geriatric primary care population, Indian J. Psychiatry, 52, S24
  2. Higgins JPT, e.a., 2011. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated march 2011]. Chichester, UK: Wiley and Sons;
  3. Jansen, R.W., Mehagnoul-Schipper, D., Hulsbos, P., Jellesma-Eggenkamp, M., Hoefnagels, W., 2003. Effect of paroxetine and nortriptyline on orthostatic and postprandial hypotension in patients 70 years of age with depressive disorders [conference presentation]. International Psychogeriatrics [abstracts from The International Psychogeriatric Association Eleventh International Congress Chicago, United States 17-22 August 2003]15 (Suppl 2).
  4. MedDRA® the Medical Dictionary for Regulatory Activities terminology is the international medical terminology developed under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). MedDRA® trademark is owned by IFPMA on behalf of ICH).

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Authors
Krause, M., Gutsmiedl, K., Bighelli, I., Schneider-Thoma, J., Chaimani, A., & Leucht, S.
Affiliations
  • University of Freiburg (DE)
  • TUM Klinikum (DE)
  • Inserm (FR)
Corresponding author
Krause, Marc
ORCID
Venue
European Neuropsychopharmacology
Publisher
Elsevier BV
Published
2019-09
Volume
29
Issue
9
Pages
1003-1022
ISSN
0924-977X (ISSN-L)
DOI
10.1016/j.euroneuro.2019.07.130
OpenAlex
W2962714707
Semantic Scholar
e6dd71851f086e60f0067e9e3bde7e14ff8fc7cf
Cited by
65
References
110
Citations by year
2026: 1 · 2025: 4 · 2024: 7 · 2023: 13 · 2022: 11 · 2021: 15 · 2020: 13 · 2019: 1
FWCI
1.28
Type
journal article
Language
en
Open access
Licence
Locations
  • European Neuropsychopharmacology (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
Funders
  • Boehringer Ingelheim
  • Bundesministerium für Bildung und Forschung (FKZ 01GL1730)
  • Teva Pharmaceutical Industries
  • Servier
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords
major depressive disorder, older adults, antidepressants, quetiapine, duloxetine, agomelatine, imipramine, vortioxetine, non-pharmacological treatment, mindfulness, memory training, adverse events, treatment response, tolerability
MeSH terms
Network Meta-Analysis, Aged, Aged, 80 and over, Antidepressive Agents, Depressive Disorder, Major, Major Depressive Disorder, Humans, Psychotherapy

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

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 ›

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