Does Duloxetine Improve Cognitive Function Independently of Its Antidepressant Effect in Patients with Major Depressive Disorder and Subjective Reports of Cognitive Dysfunction?
Open accessAbstract
Introduction. Cognitive deficits are commonly reported by patients with major depressive disorder (MDD). Duloxetine, a dual serotonin/noradrenaline reuptake inhibitor, may improve cognitive deficits in MDD. It is unclear if cognitive improvements occur independently of antidepressant effects with standard antidepressant medications.Methods. Thirty participants with MDD who endorsed cognitive deficits at screening received 12-week duloxetine treatment. Twenty-one participants completed treatment and baseline and posttreatment cognitive testing. The Cambridge Neuropsychological Test Automated Battery was used to assess the following cognitive domains: attention, visual memory, executive function/set shifting and working memory, executive function/spatial planning, decision making and response control, and verbal learning and memory.Results. Completers showed significant cognitive improvements across several domains on tasks assessing psychomotor function and mental processing speed, with additional improvements in visual and verbal learning and memory, and affective decision making and response control. Overall significance tests for executive function tasks were also significant, although individual tasks were not, perhaps due to the small sample size. Most notably, cognitive improvements were observed independently of symptom reduction on all domains except verbal learning and memory.Conclusions. Patients reporting baseline cognitive deficits achieved cognitive improvements with duloxetine treatment, most of which were independent of symptomatic improvement. This trial is registered with NCT00933439.
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TL;DR
In a 12-week open-label trial, 21 adults with major depressive disorder who reported cognitive dysfunction showed significant improvements on several CANTAB cognitive domains after duloxetine treatment. Most cognitive improvements were independent of depressive symptom reduction, except verbal learning and memory.
Key findings
- Significant domain-by-time improvements were found for Attention (F(2,19)=68.79, P<.0001), Visual Memory (F(7,14)=76.64, P<.0001), Executive Function/Set-Shifting and Working Memory (F(5,16)=80.58, P<.0001), Executive Function/Spatial Planning (F(4,17)=15.95, P<.0001), and Decision Making and Response Control (F(2,19)=802.04, P<.0001).
- Specific tasks improved: reaction time five-choice movement time (t=−3.48, P=.002), delayed matching to sample percent correct (t=5.00, P<.0001), delayed matching to sample mean correct latency (t=−3.20, P=.005), pattern recognition memory mean correct latency (t=2.27, P=.03), and affective go/no-go total omissions (t=−2.71, P=.01); significant task improvements ranged from 10% to 34%.
- Cognitive improvements were independent of symptom severity on all domains except verbal learning and memory; immediate free recall was associated with change in HRSD17 (F(1,19)=11.5, P<.004; r=.54).
- Depressive symptom severity improved from mean HRSD17 19.4 (4.4) at baseline to 8.3 (5.7) at Week 12, an average decrease of 54.5% (P<.0001); 12 of 21 completers (57.1%) were responders and remitters.
Methods
- Open-label 12-week duloxetine treatment in 30 participants with MDD aged 18–45 who endorsed cognitive deficits at screening (IDS-C30 item 15 score ≥2); 21 completed treatment and pre/post cognitive testing.
- Cognitive function was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB) across attention, visual memory, executive function/set-shifting and working memory, executive function/spatial planning, decision making and response control, and verbal learning and memory; symptom severity was assessed with HRSD17, IDS-C30, and IDS-SR30.
- Analyses used MANCOVA/MANOVA with change in HRSD17 as a covariate, followed by post hoc t-tests for individual measures when overall domain effects were significant.
Limitations
- Stated by the paper: small sample size, open-label treatment, no nondepressed control group, subjective cognitive complaints may not reflect objectively measurable pretreatment impairment in all domains, and possible practice effects or strategy development despite parallel forms.
- Stated by the paper: results are preliminary, and further work is needed to determine the best approach to measuring cognitive changes and the relationship between subjective and objective cognitive impairment in depression.
- Evident from the text: the lack of a placebo or blinded treatment arm limits causal attribution of cognitive changes to duloxetine, and the small sample likely provided insufficient power for individual executive function tasks, as the paper itself notes.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
0 of 53 cited sources checked · 0 supported · 0 flagged
- Findingown data
The most commonly reported adverse effects across all observed visits were difficulty sleeping (55.9%), headache (44.1%), poor concentration (43.5%), fatigue (43.5%), anxiety (40.0%), dry mouth (33.8%), decreased energy (33.1%), and loss of sexual desire (30.3%).
“Adverse effects most commonly reported by participants who completed the study (n = 21; reported as percent occurrence across all observed visits (n = 145)) included difficulty sleeping (55.9%), headache (44.1%), poor concentration (43.5%), fatigue (43.5%), anxiety (40.0%), dry mouth (33.8%), decreased energy (33.1%), and loss of sexual desire (30.3%).”
Quote in the paperNot a substantial claim - Findingown data
IDS Self-Report item #15 decreased from a mean of 2.05 at baseline to 0.52 after treatment, indicating subjective cognitive improvement.
“Similarly, the IDS Self-Report item (#15) decreased from a mean of 2.05 (±0.76) to 0.52 (±0.68), also indicating subjective cognitive improvement.”
Quote in the paperSubstantial claim - Findingown data
The MANCOVA for verbal learning and memory revealed a significant relationship between change in symptom severity and change in verbal learning and memory.
“The MANCOVA for verbal learning and memory revealed a significant relationship between change in symptom severity and change in verbal learning and memory (time × severity, F(1,19) = 12.1, P < .003; time × severity × verbal learning and memory, F(2,18) = 0.60, P < .56).”
Quote in the paperSubstantial claim - Findingown data
The two verbal recognition tasks (immediate and delayed) were not significantly associated with change in symptom severity.
“The two verbal recognition tasks (both immediate and delayed) were not significantly associated with change in symptom severity.”
Quote in the paperSubstantial claim - Findingown data
With the exception of the verbal immediate free recall task, cognitive improvements were independent of improvements in depressive symptom severity.
“With the exception of the verbal immediate free recall task, cognitive improvements were independent of improvements in depressive symptom severity.”
Quote in the paperSubstantial claim
- Findingown data
IDS-C30 and IDS-SR30 scores decreased from baseline means of 36.8 and 37.9 to Week 12 scores of 14.7 and 13.7, respectively.
“The IDS-C30 and IDS-SR30 scores showed similar decreases from baseline mean scores of 36.8 (8.7) and 37.9 (12.1), respectively, to Week 12 scores of 14.7 (10.0) and 13.7 (11.4).”
Quote in the paperNot a substantial claim - Findingown data
Patients reporting baseline cognitive deficits achieved cognitive improvements with duloxetine treatment.
“Patients reporting baseline cognitive deficits achieved cognitive improvements with duloxetine treatment”
Quote in the paperSubstantial claim- Rests on an assumption: Cognitive improvements observed over 12 weeks of duloxetine treatment are attributable to duloxetine rather than practice effects, regression to the mean, or natural course.
- Rests on an assumption: The CANTAB cognitive tasks are sensitive to change and not subject to practice effects over repeated administration.
- Rests on an assumption: The subjective report of cognitive deficits (IDS-C30 item #15 score ≥2) identifies patients with clinically significant cognitive dysfunction that can improve with treatment.
- Findingown data
Tasks that significantly improved following duloxetine treatment yielded percent improvements ranging from 10% to 34%.
“Tasks in this study that significantly improved following duloxetine treatment yielded percent improvements ranging from 10% to 34%.”
Quote in the paperSubstantial claim - Findingown data
There was a significant reduction in depressive symptoms with duloxetine treatment.
“As expected, there was also a significant reduction in depressive symptoms with treatment.”
Quote in the paperSubstantial claim - Findingown data
Overall significance tests for executive function tasks were significant.
“Overall significance tests for executive function tasks were also significant”
Quote in the paperSubstantial claim - Findingown data
Depressive symptom severity (HRSD17) improved significantly over 12 weeks of treatment, with mean score dropping from 19.4 at baseline to 8.3 at Week 12, an average decrease of 54.5%.
“Changes in HRSD17 over the 12 weeks of treatment showed that participants' depressive symptom severity improved significantly, with a mean score of 19.4 (4.4) at baseline, dropping to a mean score of 8.3 (5.7) at Week 12, corresponding to an average decrease of 54.5% (P < .0001).”
Quote in the paperSubstantial claim - Findingown data
Significant domain-by-time interactions were obtained for all cognitive domains assessed (Attention, Visual Memory, Executive Function/Set-Shifting and Working Memory, Executive Function/Spatial Planning, and Decision Making and Response Control) in MDD patients treated with duloxetine.
“Significant domain-by-time interactions were obtained for all of the cognitive domains assessed: Attention (F(2,19) = 68.79, P < .0001), Visual Memory (F(7,14) = 76.64, P < .0001), Executive Function/Set-Shifting and Working Memory (F(5,16) = 80.58, P < .0001), Executive Function/Spatial Planning (F(4,17) = 15.95, P < .0001), and Decision Making and Response Control (F(2,19) = 802.04, P < .0001).”
Quote in the paperSubstantial claim - Findingown data
Individual executive function tasks were not significant.
“although individual tasks were not”
Quote in the paperNot a substantial claim - Findingown data
The MANCOVAs using percent change in HRSD17 produced no significant effects in the remaining cognitive domains: Attention, Visual Memory, Executive Function/Spatial Planning, and Decision Making and Response Control.
“The results of the MANCOVAs using percent change in HRSD17 as the measure of symptom severity change produced no significant effects in the remaining cognitive domains”
Quote in the paperSubstantial claim - Findingown data
Clinician-rated cognitive function (IDS item 15-Concentration and Decision Making) improved following 12 weeks of duloxetine treatment, with mean item 15 score decreasing from 2.14 at baseline to 0.62 after treatment.
“Clinician-rated evaluation of cognitive function (based on the Inventory for Depressive Symptomatology item 15—Concentration and Decision Making) also improved following 12 weeks of duloxetine treatment. The mean item 15 score decreased from 2.14 (±0.36) at baseline to 0.62 (±0.74) after treatment.”
Quote in the paperSubstantial claim - Findingown data
The immediate free recall task was significantly associated with change in HRSD17, with a correlation of r = .54 between percent change in HRSD17 and percent change in immediate free recall.
“The immediate free recall task was significantly associated with change in HRSD17 (time × severity, F(1,19) = 11.5, P < .004), with a correlation between percent change in HRSD17 and percent change in immediate free recall of r = .54”
Quote in the paperSubstantial claim - Findingown data
The current study failed to see the expected improvements on individual tests of executive function that were observed in the Herrera-Guzmán et al. study.
“The current study failed to see the expected improvements on individual tests of executive function that were observed in the Herrera-Guzmán et al. [36] study.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [36] source
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- Premisecitation
There is evidence suggesting that cognitive impairments may be independent of symptom severity.
“there is evidence suggesting that cognitive impairments may be independent of symptom severity [37]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] source
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- Premisecitation
Functional skills are significantly impaired in depressed individuals compared to healthy control participants.
“a recent study examining performance-based assessment of functional skills (e.g., paying a bill or rescheduling an appointment) in Chinese participants with severe mental illness found that functional skills were significantly impaired in depressed individuals compared to healthy control participants [13].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] source
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- Premisecitation
Duloxetine has been shown to increase extracellular 5-HT, norepinephrine, and dopamine in rat frontal cortex.
“has been shown to increase extracellular 5-HT, norepinephrine, and dopamine in rat frontal cortex [31]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [31] 1995, Journal of Pharmacology and Experimental Therapeutics source
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- Premisecitation
Herrera-Guzmán et al. found that both duloxetine and escitalopram improved declarative memory, working memory, set shifting, spatial planning, mental processing speed, and motor performance.
“Recently, Herrera-Guzmán et al. [35, 36] compared cognitive function following treatment with either duloxetine or escitalopram and found that both improved declarative memory, working memory, set shifting, spatial planning, mental processing speed, and motor performance.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
There are many reports of cognitive impairments that remain following antidepressant treatment that successfully reduces depressive symptomatology, even when remission of depressive symptoms is obtained.
“In contrast, there are many reports of cognitive impairments that remain following antidepressant treatment that successfully reduces depressive symptomatology [19–21], even when remission of depressive symptoms is obtained [22–24].”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [19] 2006, Journal of Clinical Psychiatry source
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- Premisecitation
Both dopamine and norepinephrine have distinct roles to facilitate information processing in the prefrontal cortex.
“both neuromodulators have distinct roles to facilitate information processing in the prefrontal cortex [33, 34].”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Norepinephrine plays an important role in cognitive functioning, particularly prefrontal cortex functions such as working memory.
“Although much previous work on cognitive functioning has stressed the importance of intact dopaminergic levels, particularly with respect to functions mediated by prefrontal cortex, such as working memory, it is now being recognized that norepinephrine plays a similarly important role [33]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [33] source
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- Interpretationown data
Cognitive improvements were independent of symptom reduction on all domains except verbal learning and memory.
“Most notably, cognitive improvements were observed independently of symptom reduction on all domains except verbal learning and memory.”
- Also stated in: § 3.1. CANTAB · hedged
“Therefore the symptom severity covariate was dropped from the analysis and only the MANOVAs are reported below, indicating that the changes in cognitive function are independent of change in symptom severity.”
Quote in the paperSubstantial claim - Also stated in: § 3.1. CANTAB · hedged
- Premisecitation
The Herrera-Guzmán studies excluded individuals with an incomplete response to treatment (less than 50% reduction of HRSD17 score at Week 4).
“the Herrera-Guzmán [35, 36] studies excluded individuals with an incomplete response to treatment (defined as less than 50% reduction of Hamilton Rating Scale for Depression, 17-item [HRSD17] score at Week 4)”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationown data
The aspects of cognitive function that improved predominantly involved psychomotor speed (both movement and thinking).
“The aspects of cognitive function that improved predominantly involved psychomotor speed (both movement and thinking).”
Quote in the paperSubstantial claim - Interpretationown data
Young-to-middle-aged adults with MDD endorsing problems with concentration and/or decision making at presentation showed significant improvements in cognitive function after 12 weeks of treatment with duloxetine.
“In this study, young-to middle-aged adults with MDD endorsing problems with concentration and/or decision making at presentation showed significant improvements in cognitive function after 12 weeks of treatment with duloxetine.”
Quote in the paperSubstantial claim - Interpretationown data
For the spatial planning domain, changes in planning time were inconsistent among problems with varying numbers of moves.
“For the spatial planning domain, examination of the difference scores suggests a more complicated picture in that changes in planning time were inconsistent among problems with varying numbers of moves.”
Quote in the paperNot a substantial claim - Interpretationown data
Persons who subjectively report cognitive impairment as part of their depressive syndrome may realize cognitive improvements with duloxetine treatment.
“These data suggest that persons who subjectively report cognitive impairment as a part of their depressive syndrome may realize cognitive improvements with duloxetine treatment.”
Quote in the paperSubstantial claim - Interpretationreasoning
It is not necessarily true that endorsement of cognitive difficulties for study eligibility reflects objectively measurable pretreatment difficulties in all of the cognitive domains assessed.
“While participants were required to endorse cognitive difficulties for study eligibility, it is not necessarily true that this endorsement would reflect objectively measurable pretreatment difficulties in all of the cognitive domains assessed.”
Quote in the paperSubstantial claim - Interpretationown data
Defining improvement solely based on norms or comparisons to nondepressed controls may miss clinically meaningful improvements in cognitive function for depressed individuals.
“Defining improvement solely based on norms or comparisons to nondepressed controls may very well miss clinically meaningful improvements in cognitive function for depressed individuals.”
Quote in the paperNot a substantial claim - Study design and conductnone given
A nondepressed control group was not assessed for comparison of baseline performance.
“In addition, a nondepressed control group was not assessed for comparison of baseline performance.”
Quote in the paperSubstantial claim - Interpretationreasoning
Absence of improvement in some cognitive domains may be the result of normal baseline performance to begin with.
“Thus, absence of improvement in some domains may be the result of normal baseline performance to begin with, which cannot be addressed without a control group.”
Quote in the paperSubstantial claim - Interpretationreasoning
The failure to see expected improvements on individual executive function tests is likely due to insufficient power in this sample.
“However, we believe this is likely due to insufficient power in our sample given the fact that we found significant overall effects in the executive function domains as described above.”
Quote in the paperSubstantial claim - Interpretationown data
The results of this study support the use of duloxetine for individuals whose presentation of depression includes cognitive impairments.
“The results of this study support the use of duloxetine for individuals whose presentation of depression includes cognitive impairments.”
Quote in the paperSubstantial claim - Interpretationown data
The lack of relationship between symptom severity and cognitive performance suggests that duloxetine may exert a positive effect on cognitive function independently of depressive symptoms.
“The lack of relationship between symptom severity and cognitive performance suggests that duloxetine may exert a positive effect on cognitive function independently of depressive symptoms, consistent with previous reports suggesting the same [36].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [36] source
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- Study design and conductnone given
The current study did not solely evaluate cognition in individuals who showed a clinical response to treatment.
“they are also important in that the current study did not solely evaluate cognition in individuals who showed a clinical response to treatment.”
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- May combine two claims. 21
- Classified as probably not a substantial claim. 28
- The quote only partly states this claim. 1
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Findingown dataAffective go/no-go total commissions, immediate free recall total novel words, and immediate recognition total correct measures approached significance.
“Affective go/no-go total commissions (t = −1.96, P = 0.06) and immediate free recall total novel words (t = −2.03, P = 0.06) and immediate recognition total correct (t = 2.02, P = 0.06) measures approached significance.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataCompleters showed significant cognitive improvements across several domains on tasks assessing psychomotor function and mental processing speed, with additional improvements in visual and verbal learning and memory, and affective decision making and response control.
“Completers showed significant cognitive improvements across several domains on tasks assessing psychomotor function and mental processing speed, with additional improvements in visual and verbal learning and memory, and affective decision making and response control.”
Quote in the paperSubstantial claim- Rests on an assumption: The CANTAB cognitive tasks are sensitive to change and not subject to practice effects over repeated administration.
May combine two claims.
Findingown dataOverall effects were significant for the two executive functioning domains, but post hoc analyses did not yield significant differences on specific outcome measures.
“Interestingly, overall effects were significant for the two executive functioning domains, but post hoc analyses did not yield significant differences on specific outcome measures.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataTwelve of the 21 completers (57.1%) were responders (≥50% decrease in HRSD17) and the same individuals were remitters (HRSD17 ≤7).
“Twelve of the 21 completers (57.1%) were defined as responders (i.e., a 50% or more decrease in the HRSD17), and those same individuals were remitters, defined by a score of 7 or less on the HRSD17.”
Quote in the paperNot a substantial claimMay combine two claims.
FindingcitationDMS mean correct latency significantly improved in the current study and approached significance (P = .051) in the Herrera-Guzmán study.
“one (DMS mean correct latency) significantly improving in the current study and approaching significance (P = .051) in the Herrera-Guzmán study [35].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [35] source
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Findingown dataPost hoc analyses revealed significant improvements on specific tasks within 3 cognitive domains: Attention (reaction time five-choice movement time), Visual Memory (delayed matching to sample percent correct, delayed matching to sample mean correct latency, pattern recognition memory mean correct latency), and Decision Making and Response Control (affective go/no-go total omissions).
“Post hoc analyses revealed significant improvements on specific tasks within 3 of the cognitive domains—(t value, and significance level reported in parentheses; see Table 3 for additional details): Attention domain—reaction time five-choice movement time (t = −3.48, P = .002); Visual Memory domain-delayed matching to sample percent correct (all delays) (t = 5.00, P < .0001), delayed matching to s”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataSide effects attributed to duloxetine were less frequent, less severe, and interfered less with function at Week 12 than at Week 1.
“At Week 12, side effects were less frequent (mean score = 1.5 ± 2.0, corresponding to 17.5% of the time), less severe (mean score = 1.1 ± 1.7, corresponding to slightly over “trivial”) and interfered less with function (mean score = 0.5 ± 1.0, corresponding to less than “minimal”).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCognitive deficits are commonly reported by patients with major depressive disorder.
“Cognitive deficits are commonly reported by patients with major depressive disorder (MDD) [1, 2]”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe cognitive impairments most commonly associated with major depressive disorder are in executive function, selective attention, and verbal learning.
“The impairments most commonly associated with MDD are in the domains of executive function, selective attention, and verbal learning [1, 3].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [1] 1997, Journal of Clinical and Experimental Neuropsychology source
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- cites [3] 2001, Neuropsychiatry, Neuropsychology and Behavioral Neurology
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PremisecitationGeneralized psychomotor slowing can impact performance across several cognitive processes and domains.
“generalized psychomotor slowing [4, 5] can also impact performance across several cognitive processes and domains.”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationImpaired cognition is likely associated with difficulties in everyday tasks, contributing to psychosocial and functional impairments, reduced productivity, and disability in major depressive disorder.
“Impaired cognition is likely associated with difficulties in everyday tasks contributing to the high degree of psychosocial and functional impairments [6–8], reduced productivity [9], and disability associated with MDD [10, 11].”
Quote in the paperNot a substantial claim0 of 6 sources checked- cites [6] 2000, Archives of General Psychiatry source
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PremisecitationOne study demonstrated improvements in cognitive function with duloxetine treatment, with effects limited primarily to improved verbal learning, in elderly patients with major depressive disorder.
“One study has previously demonstrated improvements in cognitive function with duloxetine treatment, with effects limited primarily to improved verbal learning, but this study was also focused on elderly patients with MDD [16].”
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PremisecitationIn younger depressed subjects, SSRI treatment yielded cognitive improvements in declarative memory, psychomotor speed, and attention.
“In studies conducted with younger depressed subjects, SSRI treatment again yielded cognitive improvements in declarative memory, psychomotor speed, and attention”
Quote in the paperNot a substantial claim0 of 2 sources checkedClassified as probably not a substantial claim.
PremisecitationEpisodic memory and processing speed improvements were at least partially independent of improvements in depressive symptom severity.
“episodic memory and processing speed improvements were reported to be at least partially independent of improvements in depressive symptom severity [35].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [35] source
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PremisecitationDuloxetine is a well-tolerated, efficacious SNRI antidepressant.
“Duloxetine is a well-tolerated, efficacious [28–30] SNRI antidepressant”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationTreatment with selective serotonin reuptake inhibitors has resulted in improved attention, memory, and learning in depression.
“Treatment with selective serotonin reuptake inhibitors (SSRIs) has resulted in improved attention, memory, and learning [14]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] 2002, Journal of Clinical Psychiatry source
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PremisecitationThere is also evidence suggesting that changes in cognitive function are associated with symptomatic improvement.
“there is also evidence suggesting that changes in cognitive function are associated with symptomatic improvement [15, 38, 39].”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationDuloxetine has been associated with serotonergic and noradrenergic reuptake in humans.
“has been associated with serotonergic and noradrenergic reuptake in humans [32].”
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PremisecitationDuloxetine treatment resulted in greater improvements in declarative and working memory than escitalopram.
“duloxetine treatment resulted in greater improvements in declarative and working memory than those achieved with escitalopram [35]”
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PremisecitationSimilar cognitive improvements have been obtained when comparing fluoxetine or reboxetine treatment.
“similar results have been obtained when comparing cognitive performance following treatment with fluoxetine or the selective noradrenergic reuptake inhibitor, reboxetine [15].”
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PremisecitationResidual cognitive impairment may contribute to increased risk of relapse, impaired quality of life, and poorer overall prognosis.
“residual cognitive impairment may contribute to increased risk of relapse, impaired quality of life, and poorer overall prognosis [6, 25, 26].”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
Interpretationown dataSpecific improvements were noted on tasks assessing visual memory, decision making/response control for emotionally laden information, and verbal recognition memory.
“Specific improvements were also noted on tasks assessing visual memory, decision making/response control for emotionally laden information, and verbal recognition memory.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataTwo participants withdrew consent and were lost to follow-up.
“Two participants withdrew consent and were lost to followup.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenData were included in the analysis based on the intent-to-treat principle.
“data was included in the analysis based on the intent-to-treat principle.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataSix participants withdrew due to intolerable side effects.
“Six had intolerable side effects”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataPsychomotor and mental processing speed may be improved with duloxetine treatment, spanning across several types of cognitive domains, and these improvements are not solely related to depressive symptom reduction.
“Specifically, psychomotor and mental processing speed may be improved with duloxetine treatment, spanning across several types of cognitive domains, and these improvements are not solely related to depressive symptom reduction.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataOne serious adverse event occurred (acute pancreatitis secondary to gallstone obstruction).
“One serious adverse event occurred for a participant who had acute pancreatitis secondary to gallstone obstruction.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationBoth the current study and the Herrera-Guzmán studies noted improvements in psychomotor speed and mental processing spanning several cognitive domains, with RTI five-choice movement time and PRM mean correct latency significantly improving in both studies.
“First, both studies noted improvements in psychomotor speed and mental processing that spanned several cognitive domains, with two of the individual tasks (RTI five-choice movement time and PRM mean correct latency) significantly improving in both studies”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataNine participants withdrew prior to study completion.
“Nine participants withdrew prior to study completion.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationBoth the current study and the Herrera-Guzmán study noted significant improvements in verbal learning, a finding also obtained by Raskin et al. in elderly patients with MDD.
“Both studies noted significant improvements in verbal learning as well, a finding that was also obtained by Raskin et al. [16] in their examination of duloxetine on cognitive function in elderly patients with MDD.”
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Interpretationown dataThe overall effects in the Executive Memory domains indicate combined effects when all measures are examined collectively, but the lack of significance for any individual test may indicate insufficient power to detect significant differences for any given individual task alone.
“The overall effects in the Executive Memory (Set-shifting and Working Memory and Spatial Planning) domains indicate that there were combined effects when all measures are examined collectively, but the lack of significance for any individual tests may indicate there was insufficient power to detect significant differences for any given individual task alone.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.
Study design and conductown dataOf 30 participants who began study medication, 21 completed all 12 weeks of study participation.
“Thirty participants were found to be eligible for the study, received a baseline evaluation, and began study medication.”
- Also stated in: § 3. Results · plain
“Twenty-one participants completed all 12 weeks of study participation.”
Quote in the paperNot a substantial claim- Also stated in: § 3. Results · plain
Classified as probably not a substantial claim.
Study design and conductnone givenCANTAB was administered by raters who were blinded to symptom severity assessments.
“CANTAB was used to assess pre- and post-treatment cognitive function and was administered by raters who were blinded to symptom severity assessments.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataFor the set-shifting and working memory domain, changes were occurring in the expected direction, but there may have been insufficient power to detect differences at the level of individual outcomes.
“Examination of the individual difference scores suggests that for the set-shifting and working memory domain, changes were occurring in the expected direction, but there may have been insufficient power to detect differences at the level of individual outcomes.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductreasoningCognitive outcome measures were grouped into domains and analyzed via separate multivariate analyses to account for multiple comparisons.
“The remaining measures from the CANTAB battery that met analysis criteria were grouped into sets based on the cognitive domains they represented and were analyzed via separate multivariate analyses (MANCOVA and/or MANOVA, as described below) to account for multiple comparisons.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningAge, education, and estimated intelligence were not needed as covariates because participants served as their own control.
“Note that age, education, and estimated intelligence were not needed because participants served as their own control.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenSymptom severity measures were collected by evaluators who were blind to the results and status of cognitive testing.
“Symptom severity measures were collected at each study visit by evaluators who were blind to the results and status of cognitive testing.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningIt is conceivable that duloxetine may also be a potential augmenting agent for depressed individuals with residual cognitive symptoms following initial antidepressant treatment.
“Therefore, it is conceivable that duloxetine may also be a potential augmenting agent for depressed individuals with residual cognitive symptoms following initial antidepressant treatment.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductnone givenLimitations of this study include the small sample size and open-label treatment.
“Limitations of this study include the small sample size and open-label treatment.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningThe approach used in this study follows what is most likely to be effectively implemented in clinical practice.
“The approach used in this study follows what is most likely to be effectively implemented in clinical practice.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataImprovements were observed in subjective, clinician-rated, and objective cognitive assessments following treatment, suggesting that assessment of subjective functioning may be a useful proxy for assessing cognitive impairment.
“Improvements were observed in all of these areas following treatment, suggesting that assessment of subjective functioning may be a useful proxy for assessing cognitive impairment.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductnone givenIn the current study, participants served as their own control.
“However, in the current study, participants served as their own control”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataBoth the current study and the Herrera-Guzmán studies observed cognitive improvements that were independent of symptom severity.
“Both studies also observed cognitive improvements that were independent of symptom severity.”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
Study design and conductreasoningParallel forms were used for available tests in an attempt to avoid practice effects, but the possibility of practice effects cannot be completely eliminated, particularly for tests for which only the clinical version was available.
“Parallel forms were used for available tests in an attempt to avoid practice effects, but the possibility of practice effects cannot be completely eliminated, particularly for those tests for which only the clinical version was available.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
InterpretationreasoningObserved improvements may have been due to practice effects and/or the development of an efficient problem-solving strategy for the task.
“Another potential limitation of this study is the possibility that observed improvements were due to practice effects and/or the development of an efficient problem-solving strategy for the task”
Quote in the paperSubstantial claim
The paper relies on this without support.
Cognitive improvements observed over 12 weeks of duloxetine treatment are attributable to duloxetine rather than practice effects, regression to the mean, or natural course.
“Patients reporting baseline cognitive deficits achieved cognitive improvements with duloxetine treatment”
The paper relies on this without support.
The CANTAB cognitive tasks are sensitive to change and not subject to practice effects over repeated administration.
“CANTAB was used to assess pre- and post-treatment cognitive function”
The paper relies on this without support.
The subjective report of cognitive deficits (IDS-C30 item #15 score ≥2) identifies patients with clinically significant cognitive dysfunction that can improve with treatment.
“A unique feature of this study design was the entrance criterion requiring participants to subjectively report significant cognitive impairment.”
The paper relies on this without support.
The sample of 21 completers is representative of the target population of young- to middle-aged adults with MDD and subjective cognitive deficits.
“Twenty-one participants completed all 12 weeks of study participation.”
The paper relies on this without support.
No gold standard screening approach exists for cognitive dysfunction that is representative of impairment on all domains thought to be associated with MDD.
“Currently no gold standard screening approach exists for cognitive dysfunction that is representative of impairment on all domains thought to be associated with MDD.”
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?
Some studies found improvements in selective attention with venlafaxine and with duloxetine, but the results have been mixed.
“Some studies have found improvements in selective attention with venlafaxine122 and with duloxetine125, but the results have been mixed99,100.”
From Paying attention to attention in depression (2019) · cites this paper as [125]
Statistics that don’t add up
Each reported p-value recomputed from its test statistic and degrees of freedom.
Inconsistent p-value: F(6,15) = .58, p < .72
MinorThe paper reports p < .72 here; recomputing from the test statistic and its degrees of freedom gives p = .741. The check cannot tell whether the statistic or the p-value is the misprint.
Reported p < .72 · recomputed p = .741
“F(6,15) = .58, P < .72”
Statistics recomputed
Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.
- Doesn’t add upF(6, 15) = 0.58reported p < .72 · recomputed p = .741
“F(6,15) = .58, p < .72”
- ConsistentF(1, 19) = 12.1reported p < .003 · recomputed p = .003
“F(1,19) = 12.1, p < .003”
- ConsistentF(2, 18) = 0.6reported p < .56 · recomputed p = .559
“F(2,18) = 0.60, p < .56”
- ConsistentF(1, 19) = 11.5reported p < .004 · recomputed p = .003
“F(1,19) = 11.5, p < .004”
- ConsistentF(1, 19) = 0.17reported p < .69 · recomputed p = .685
“F(1,19) = .17, p < .69”
- ConsistentF(2, 18) = 0.34reported p < .72 · recomputed p = .716
“F(2,18) = .34, p < .72”
- ConsistentF(1, 19) = 0.22reported p < .65 · recomputed p = .644
“F(1,19) = .22, p < .65”
- ConsistentF(7, 13) = 0.55reported p < .79 · recomputed p = .783
“F(7,13) = .55, p < .79”
- ConsistentF(1, 19) = 1.27reported p < .28 · recomputed p = .274
“F(1,19) = 1.27, p < .28”
- ConsistentF(1, 19) = 0.13reported p < .73 · recomputed p = .722
“F(1,19) = .13, p < .73”
- ConsistentF(6, 15) = 1.43reported p < .27 · recomputed p = .267
“F(6,15) = 1.43, p < .27”
- ConsistentF(2, 19) = 68.79reported p < .0001 · recomputed p < .001
“F(2,19) = 68.79, p < .0001”
- ConsistentF(7, 14) = 76.64reported p < .0001 · recomputed p < .001
“F(7,14) = 76.64, p < .0001”
- ConsistentF(5, 16) = 80.58reported p < .0001 · recomputed p < .001
“F(5,16) = 80.58, p < .0001”
- ConsistentF(4, 17) = 15.95reported p < .0001 · recomputed p < .001
“F(4,17) = 15.95, p < .0001”
- ConsistentF(2, 19) = 802.04reported p < .0001 · recomputed p < .001
“F(2,19) = 802.04, p < .0001”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Self-check results appear here once an independent check has confirmed them.
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Cited by
Sorted by citations
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- Authors
- Greer, T. L., Sunderajan, P., Grannemann, B. D., Kurian, B. T., & Trivedi, M. H.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Greer, Tracy L.
- Venue
- Depression Research and Treatment
- Publisher
- Wiley
- Published
- 2014
- Volume
- 2014
- Pages
- 1-13
- ISSN
- 2090-1321 (ISSN-L)
- 2090-133X
- PMC
- PMC3915915
- OpenAlex
- W2016400778
- Semantic Scholar
- debaef54d4f82beb0e21732cffdce99ae475b1a8
- Cited by
- 63
- References
- 52
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 1 · 2022: 6 · 2021: 1 · 2020: 3 · 2019: 6 · 2018: 4 · 2017: 11 · 2016: 6 · 2015: 8 · 2014: 7
- FWCI
- 7.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Depression Research and Treatment (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- duloxetine, major depressive disorder, cognitive impairment, antidepressant effects, serotonin-norepinephrine reuptake inhibitors, executive function, processing speed, verbal learning and memory, decision-making, response control, attention, visual memory
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