Lead Investigator: Florian Naudet, CHU Rennes
Title of Proposal Research: Tolerability of duloxetine in the elderly and in younger adults: a systematic review and individual patient data meta-analysis of randomized controlled trials versus placebo
Vivli Data Request: 8760, 4112
Funding Source: The project received in 2021 a grant from the PHRC national-Hospital Clinical Research Program
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Duloxetine is a medication which has been approved for a wide range of pathologies by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), namely major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, chronic musculoskeletal pain and stress urinary incontinence. These diseases represent a major public health burden for elderly population. Several guidelines recommend the use of duloxetine as a first-line medication for these diseases in the elderly while some formally proscribe its use.
As a matter of fact, good practice guidelines of duloxetine use are under debate, notably because of mixed evidence for a favorable risk-benefit balance in older populations. For instance, duloxetine has been associated with both the highest response rate for major depressive disorder in old-age population compared to other serotoninergic antidepressants (antidepressant drugs that involve serotonin, a chemical that carries messages between the brain and other parts of the body to enhance satisfaction, happiness and optimism), and the highest risk of adverse events (AE, i.e. undesired effects of a drug), supported by several meta-analyses which concluded to a disfavoring risk-benefit balance for duloxetine compared to placebo. More precisely, the European Public Assessment Report of duloxetine warns of an increased amount of falls and hyponatremia (low concentration of sodium in the blood) in the elderly. However, many subgroup analyses of pilot trials did not find differences in tolerability between old and young adults, maybe due to the small effective of elderly participants within these studies.
Altogether, it seems that the tolerability of duloxetine needs clarification especially if AE are more frequent in elderly compare to adults. The scope of this meta-analysis is intended to inform clinical decision-making for a wide range of conditions for the elderly population. Therefore, we would like to determine whether old age is significantly associated to a higher risk of AE under duloxetine than younger adults, by an individual participant meta-analysis of randomized controlled trials of any condition with an FDA or EMA approval of use of duloxetine.
Requested Studies:
Duloxetine 20/30 mg vs. Placebo in Major Depression
Sponsor: Eli Lilly and Company
Sponsor ID: F1J-MC-HMAH
A Double-Blind, Placebo- and Clomipramine-Controlled Study of Duloxetine in Patients with Major Depression
Sponsor: Eli Lilly and Company
Sponsor ID: F1J-MC-HMAI
Duloxetine Hydrochloride (LY248686) Protocol F1J-US-HMCB Duloxetine Once-Daily Dosing Versus Placebo in Patients With Major Depression and Pain
Sponsor: Eli Lilly and Company
Study ID: NCT00036335
Sponsor ID: 6353
Duloxetine Versus Escitalopram and Placebo in the Treatment of Patients With Major Depression
Sponsor: Eli Lilly and Company
Study ID: NCT00073411
Sponsor ID: 7978
Duloxetine Versus Placebo in the Prevention of Recurrence of Major Depressive Disorder
Sponsor: Eli Lilly and Company
Study ID: NCT00105989
Sponsor ID: 8606
Duloxetine Versus Placebo in the Long-Term Treatment of Patients With Late-Life Major Depression
Sponsor: Eli Lilly and Company
Study ID: NCT00406848
Sponsor ID: 10815
A Phase 4, 8-Week, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy of Duloxetine 60 mg Once Daily in Outpatients With Major Depressive Disorder and Associated Painful Physical Symptoms
Sponsor: Eli Lilly and Company
Study ID: NCT01000805
Sponsor ID: 13399
Duloxetine Versus Placebo in the Acute Treatment of Patients With Major Depressive Disorder and Associated Painful Physical Symptoms
Sponsor: Eli Lilly and Company
Study ID: NCT01070329
Sponsor ID: 13630
Validation of Daily Telephone Self-Assessment in the Study of Antidepressant Treatment Outcome
Sponsor: Eli Lilly and Company
Sponsor ID: H8I-MC-HQAC
Duloxetine Hydrochloride Once Daily Compared With Placebo in the Treatment of Generalized Anxiety Disorder
Sponsor: Eli Lilly and Company
Study ID: NCT00475969
Sponsor ID: 6089
A Comparison of Duloxetine Hydrochloride, Venlafaxine Extended Release, and Placebo in the Treatment of Generalized Anxiety Disorder
Sponsor: Eli Lilly and Company
Study ID: NCT00122850
Sponsor ID: 7107
Duloxetine 60 to 120 mg Once Daily Compared With Placebo in the Prevention of Relapse in Generalized Anxiety Disorder
Sponsor: Eli Lilly and Company
Study ID: NCT00122863
Sponsor ID: 7108
A Comparison of Duloxetine Hydrochloride, Venlafaxine Extended Release, and Placebo in the Treatment of Generalized Anxiety Disorder
Sponsor: Eli Lilly and Company
Study ID: NCT00122837
Sponsor ID: 7106
Duloxetine Hydrochloride 60 mg or 120 mg Once Daily Compared With Placebo in Patients With Generalized Anxiety Disorder
Sponsor: Eli Lilly and Company
Study ID: NCT00122824
Sponsor ID: 5075
Duloxetine Versus Placebo in the Treatment of Fibromyalgia Patients With or Without Major Depressive Disorder
Sponsor: Eli Lilly and Company
Study ID: NCT00489073
Sponsor ID: 6158
A Randomized, Double-Blind Comparison of Duloxetine 30 mg QD and Placebo in Adult Patients With Fibromyalgia (HMGG)
Sponsor: Eli Lilly and Company
Study ID: 12873
Sponsor ID: NCT00965081
Duloxetine Versus Placebo in the Treatment of Fibromyalgia Patients With or Without Major Depressive Disorder
Sponsor: Eli Lilly and Company
Sponsor ID: F1J-MC-HMBO
Duloxetine Versus Placebo in the Treatment of Patients With Painful Diabetic Neuropathy
Sponsor: Eli Lilly and Company
Study ID: NCT00058968
Sponsor ID: 4097
A Dose Response Study of Duloxetine versus Placebo in Patients with Painful Diabetic Neuropathy
Sponsor: Eli Lilly and Company
Sponsor ID: F1J-MC-HMAW
Duloxetine Versus Placebo in the Treatment of Patients With Diabetic Peripheral Neuropathic Pain in China
Sponsor: Eli Lilly and Company
Study ID: NCT00408993
Sponsor ID: 10599
Treatment of Patients With Diabetic Peripheral Neuropathic Pain in China: Duloxetine Versus Placebo
Sponsor: Eli Lilly and Company
Study ID: NCT01179672
Sponsor ID: 13649
Effect of Duloxetine 60 mg to 120 mg Once Daily in Patients With Chronic Low Back Pain
Sponsor: Eli Lilly and Company
Study ID: NCT00424593
Sponsor ID: 10544
Protocol F1J-MC-HMEO Duloxetine Versus Placebo in the Treatment of Chronic Low Back Pain
Sponsor: Eli Lilly and Company
Study ID: NCT00408876
Sponsor ID: 10545
Effect of Duloxetine 60 mg Once Daily Versus Placebo in Patients With Chronic Low Back Pain
Sponsor: Eli Lilly and Company
Study ID: NCT00767806
Sponsor ID: 12360
Duloxetine 60 to 120 mg Versus Placebo in the Treatment of Patients With Osteoarthritis Knee Pain
Sponsor: Eli Lilly and Company
Study ID: NCT00408421
Sponsor ID: 10546
Protocol F1J-MC-HMFG Duloxetine 60 to 120 mg Versus Placebo in the Treatment of Patients With Osteoarthritis Knee Pain
Sponsor: Eli Lilly and Company
Study ID: NCT00433290
Sponsor ID: 11198
A Phase 3b Study to Assess the Efficacy of Duloxetine 60 mg Once Daily Compared With Placebo on the Reduction of Pain Caused by Osteoarthritis of the Knee, in a 13-week, Double-blind, Randomized Study
Sponsor: Eli Lilly and Company
Study ID: NCT00945945
Sponsor ID: 13214
A Randomised, Double-blind, Parallel-group, Placebo-controlled, Duloxetine-referenced, Fixed-dose Study Evaluating the Efficacy and Safety of Three Dosages of [Vortioxetine] Lu AA21004, in Acute Treatment of Major Depressive Disorder
Sponsor: H Lundbeck A/S
Study ID: NCT00635219
Sponsor ID: 11984A
A Randomised, Double-blind, Parallel-group, Placebo-controlled, Duloxetine-referenced, Fixed-dose Study Evaluating the Efficacy and Safety of Lu AA21004 (15 and 20 mg/Day) in the Acute Treatment of Adult Patients With Major Depressive Disorder
Sponsor: H Lundbeck A/S
Study ID: NCT01140906
Sponsor ID: 13267A
A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Active-Referenced, Fixed-Dose Study Comparing the Efficacy and Safety of 2 Doses of Lu AA21004 in Acute Treatment of Adults With Major Depressive Disorder
Sponsor: Takeda
Study ID: NCT00672620
Sponsor ID: LuAA21004_304
A Phase 3, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Duloxetine-Referenced, Fixed-Dose Study Comparing the Efficacy and Safety of 2 Doses (15 and 20 mg) of Lu AA21004 in Acute Treatment of Adults With Major Depressive Disorder
Sponsor: Takeda
Study ID: NCT01153009
Sponsor ID: LuAA21004_315
A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Active-Referenced, Flexible Dose Study on the Efficacy of Lu AA21004 on Cognitive Dysfunction in Adult Subjects With Major Depressive Disorder (MDD)
Sponsor: Takeda
Study ID: NCT01564862
Sponsor ID: LuAA21004_202
(Note: Additional studies added as part of Data Request 8760)
Effect of Duloxetine 60mg Once Daily in Patients With Chronic Pain Due to Osteoarthritis in China
Data Contributor: Lilly
Study ID: NCT01931475
Sponsor ID: 13494
Duloxetine Versus Placebo and Paroxetine in the Acute Treatment of Major Depression
Data Contributor: Lilly
Study ID: F1J-MC-HMAT(A)
Sponsor ID: F1J-MC-HMAT(A)
Duloxetine Versus Placebo and Paroxetine in the Acute Treatment of Major Depression
Data Contributor: Lilly
Study ID: F1J-MC-HMAT(B)
Sponsor ID: F1J-MC-HMAT(B)
Duloxetine Versus Placebo and Paroxetine in the Treatment of Major Depression
Data Contributor: Lilly
Study ID: F1J-MC-HMAY(A)
Sponsor ID: F1J-MC-HMAY(A)
Duloxetine Versus Placebo and Paroxetine in the Treatment of Major Depression
Data Contributor: Lilly
Study ID: F1J-MC-HMAY(B)
Sponsor ID: F1J-MC-HMAY(B)
Duloxetine Once-Daily Dosing Versus Placebo in the Acute Treatment of Major Depression
Data Contributor: Lilly
Study ID: F1J-MC-HMBH(A)
Sponsor ID: F1J-MC-HMBH(A)
Duloxetine Once-Daily Dosing Versus Placebo in the Acute Treatment of Major Depression
Data Contributor: Lilly
Study ID: F1J-MC-HMBH(B)
Sponsor ID: F1J-MC-HMBH(B)
Duloxetine/Placebo in Major Depressive Disorder
Data Contributor: Lilly
Study ID: F1J-MC-HMAG
Sponsor ID: F1J-MC-HMAG
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Duloxetine-Referenced, Parallel-Group Study to Evaluate the Efficacy and Safety of 2 Fixed Doses (50mg, 100mg) of Desvenlafaxine Sustained-Release Tablets in Adult Outpatients With Major Depressive Disorder
Data Contributor: Pfizer Inc.
Study ID: NCT00384033
Sponsor ID: 3151A1-335
Dose Response Study of Duloxetine Versus Placebo in the Treatment of Fibromyalgia Syndrome
Data Contributor: Lilly
Study ID: NCT00190866
Sponsor ID: 6222
Flexible Dosed Duloxetine Versus Placebo in the Treatment of Fibromyalgia
Data Contributor: Lilly
Study ID: NCT00673452
Sponsor ID: 12220
Duloxetine 60/120mg Versus Placebo in the Treatment of Fibromyalgia Syndrome
Data Contributor: Lilly
Study ID: NCT00233025
Sponsor ID: 9072
A Randomized, Placebo-Controlled Trial of Duloxetine Added to Nonsteroidal Anti-inflammatory Drugs in Patients With Knee Pain Due to Osteoarthritis Who Have Had Suboptimal Response to Nonsteroidal Anti-inflammatory Drug Treatment.
Data Contributor: Lilly
Study ID: NCT01018680
Sponsor ID: 12909
Duloxetine Hydrochloride versus Placebo and Oxybutynin in Patients with Symptoms of Urinary Urgency and Frequency
Data Contributor: Lilly
Study ID: F1J-MC-SAAL
Sponsor ID: F1J-MC-SAAL
Duloxetine for Urinary Incontinence: A Multiple-Dose Study for Efficacy and Safety
Data Contributor: Lilly
Study ID: F1J-MC-SAAB
Sponsor ID: F1J-MC-SAAB
A Study of Duloxetine Hydrochloride Versus Placebo in Patients with Urinary Urgency and Proven Detrusor Overactivity
Data Contributor: Lilly
Study ID: F1J-MC-SAAH
Sponsor ID: F1J-MC-SAAH
Efficacy and Safety of Duloxetine Compared With Placebo in Women With Symptoms of Mixed Urinary Incontinence.
Data Contributor: Lilly
Study ID: NCT00190814
Sponsor ID: 6192
Biomechanical Effects of Duloxetine on Bladder Function and Sphincter Resistance During the Emptying Phase and on Urethral Function During the Filling Phase of the Micturition Cycle in Women With Pure Genuine Stress Incontinence
Data Contributor: Lilly
Study ID: F1J-MC-SBAB
Sponsor ID: F1J-MC-SBAB
Efficacy and Safety of Duloxetine Compared With Placebo, Pelvic Floor Muscle Training, and Combined Duloxetine/Pelvic Floor Muscle Training in Subjects With Moderate to Severe Stress Urinary Incontinence
Data Contributor: Lilly
Study ID: F1J-MC-SBAF
Sponsor ID: F1J-MC-SBAF
Efficacy and Safety of Duloxetine Compared With Placebo in Subjects Electing Surgery for Severe Pure Genuine Stress Incontinence
Data Contributor: Lilly
Study ID: F1J-MC-SBAM
Sponsor ID: F1J-MC-SBAM
The Effectiveness of Duloxetine Compared With Placebo in the Treatment of Predominant Stress Urinary Incontinence
Data Contributor: Lilly
Study ID: F1J-MC-SBBR
Sponsor ID: F1J-MC-SBBR
The Safety and Effectiveness of Duloxetine Compared With Placebo and Its Long-Term Safety and Efficacy in the Treatment of Predominant Stress Urinary Incontinence
Data Contributor: Lilly
Study ID: F1J-EW-SBCC
Sponsor ID: F1J-EW-SBCC
Efficacy and Safety of Duloxetine Compared With Placebo in Subjects With Stress Urinary Incontinence
Data Contributor: Lilly
Study ID: F1J-MC-SBBT
Sponsor ID: F1J-MC-SBBT
Efficacy and Safety of Duloxetine Compared With Placebo in Subjects With Stress Urinary Incontinence
Data Contributor: Lilly
Study ID: F1J-MC-SBBU
Sponsor ID: F1J-MC-SBBU
Efficacy and Safety of Duloxetine Compared with Placebo in Subjects with Stress Urinary Incontinence
Data Contributor: Lilly
Study ID: F1J-MC-SBAV
Sponsor ID: F1J-MC-SBAV
Efficacy and Safety of Duloxetine Compared with Placebo in Subjects with Stress Urinary Incontinence
Data Contributor: Lilly
Study ID: F1J-MC-SBAT
Sponsor ID: F1J-MC-SBAT
Duloxetine Versus Placebo in Patients with Urinary Incontinence: Assessment of Subjective and Objective Parameters
Data Contributor: Lilly
Study ID: F1J-MC-SAAA
Sponsor ID: F1J-MC-SAAA
Efficacy and Safety of Duloxetine Compared with Placebo in Subjects with Stress Urinary Incontinence
Data Contributor: Lilly
Study ID: F1J-MC-SBAX
Sponsor ID: F1J-MC-SBAX
Efficacy and Safety of Duloxetine Compared with Placebo in Subjects with Symptoms of Bladder Overactivity Due to Pure Detrusor Instability or Sensory Urgency
Data Contributor: Lilly
Study ID: F1J-MC-SBBL
Sponsor ID: F1J-MC-SBBL
Prospective Outcomes of Duloxetine in Usual Naturalistic Care in Women with Stress Urinary Incontinence
Data Contributor: Lilly
Study ID: F1J-MC-SBBA
Sponsor ID: F1J-MC-SBBA
A Phase 4, 8-Week, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy of Duloxetine 60 mg Once Daily in Outpatients With Major Depressive Disorder and Associated Painful Physical Symptoms
Data Contributor: Lilly
Study ID: NCT01000805
Sponsor ID: 13399
A Global, Multicenter, Randomized, Double-Blind Placebo Controlled Study Comparing the Safety and Efficacy of ABT-894, Duloxetine and Placebo in Subjects With Diabetic Neuropathic Pain
Data Contributor: AbbVie
Study ID: NCT00507936, M06-850
Sponsor ID: NCT00507936, M06-850
A Randomized Double Blind Study Evaluating Duloxetine in Outpatients With MDD and Pain
Data Contributor: Lilly
Study ID: NCT00191919, F1J-BI-HMDH
Sponsor ID: NCT00191919, F1J-BI-HMDH