Twitter Facebook LinkedIn
Center for Global Research Data

Tolerability of duloxetine in the elderly and in adults: a systematic review and individual patient data meta-analysis of randomized controlled trials versus placebo

Lead Investigator: Florian Naudet, CHU Rennes
Title of Proposal Research: Tolerability of duloxetine in the elderly and in adults: a systematic review and individual patient data meta-analysis of randomized controlled trials versus placebo
Vivli Data Request: 4112
Funding Source: None
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, and the highest risk of adverse events (AE), 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 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. Recently, meta-regression analyses from Cipriani et al. (2018) confirm previous results of efficacy but possible excessive risks.

Indeed, they found a significative association between mean age of participants and response to duloxetine (OR = 1.86, CI 95% = 1.66-2.08) with a trend of association between age and number of drop-outs (OR = 1.10, CI 95% = 0.97-1.24) (12). Altogether, it seems that the tolerability of duloxetine needs clarification especially if AE are more frequent in elderly compare to adults. 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