A Study Evaluating Duloxetine in Patients Hospitalized for Severe Depression

An Eight-Week, Randomized, Double Blind, Two Parallel Groups, Study to Assess Clinical Response of Duloxetine 60 mg and 120 Per Day in Patients Hospitalized for Severe Depression

An eight-week, randomized, double blind, two parallel groups, study to assess clinical response of duloxetine 60 milligrams (mg) and 120 mg per day in patients hospitalized for severe depression.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Duloxetine hydrochloride; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 339
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Besancon, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Bordeaux, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Bully les Mines, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Chateau-Gontier, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Dijon, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Dole, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Fains Veel, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Jarnac, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • La Charite sur Loire, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • La Rochelle, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Limoges, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Marseille, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Montberon, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Montpellier, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Nimes, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Paris, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Saint-Dizier, France
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
• Italy
  • Firenze, Italy
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Foggia, Italy
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Messina, Italy
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Milano, Italy
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Pisa, Italy
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Roma, Italy
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Siena, Italy
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
• Russian Federation
  • Kazan, Russian Federation
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Lipetsk, Russian Federation
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Moscow, Russian Federation
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Nizhny Novgorod, Russian Federation
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Saratov, Russian Federation
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • St. Petersburg, Russian Federation
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
• South Africa
  • Bryanston, South Africa
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Cape Town, South Africa
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • George, South Africa
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Krugersdorp, South Africa
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician
  • Pretoria, South Africa
    • For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559 or 1-317-615-4559), Mon-Fri, 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST) or speak with your personal physician

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Male or female patients of ≥ 18 years of age that meet criteria for severe Major Depressive Disorder, without psychotic features (according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, [DSM-IV] and confirmed by Mini International Neuropsychiatric Interview [MINI]).

• With a total score Montgomery-Asberg Depression Rating Scale (MADRS) ≥ 30 and 6-item Hamilton Depression Rating Scale (HAMD-6) ≥ 12 and Clinical Global Impression of Severity (CGI-Severity) ≥ 4 at both screening and baseline.
• Requirement of hospitalization (not for social or other non-medical reasons) at screening visit and at least up to Visit 4.
• Patients willing and able to comply with the requirement for hospitalization and with all scheduled visits, tests and procedures required by the protocol.
• Informed consent document must be signed at screening visit, in accordance with Good Clinical Practice (GCP) and local regulatory requirements, prior to any study procedure.

Exclusion Criteria:

• More than two previous episodes of major depression that did not respond (according to investigator's opinion) to adequate doses and duration of two different antidepressant therapies.
• Lack of response to at least two antidepressant therapies given at adequate doses for at least 6 weeks for the current depressive episode.
• Concurrent presence of symptoms fulfilling criteria for any Axis I disorder other than anxiety disorders (with exception of the Obsessive-Compulsive Disorder (OCD)) or Major Depressive Disorder, in the investigator's judgment.
• Any previous diagnosis of a bipolar disorder, schizophrenia or OCD.
• Depression with catatonic features (according to DSM-IV), depression with post-partum onset, or organic mental disorders.
• The presence of an Axis II disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Duloxetine Hydrochloride (60 mg); Up to Week 4: 60 milligrams (mg) every morning and placebo every evening, by mouth (PO). Week 4 to Week 8: Responders continued on same dose as before; Nonresponders received 60 mg every morning and 60 mg every evening added to the placebo	Drug: Duloxetine hydrochloride; 60 mg once or twice a day, by mouth; Other Names: Cymbalta; LY248686; Drug: Placebo; placebo capsule by mouth
Experimental: Duloxetine Hydrochloride (120 mg); Up to Week 4: 60 mg every morning and 60 mg every evening, PO. Week 4 to Week 8: Responders continued on same dose as before; Nonresponders continued as before with a placebo capsule added to the evening dose	Drug: Duloxetine hydrochloride; 60 mg once or twice a day, by mouth; Other Names: Cymbalta; LY248686; Drug: Placebo; placebo capsule by mouth

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to 4 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).	Baseline to Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline	The HAMD-6 (Items 1,2,7,8,10,13 from the 17-item HAMD) evaluates "core" symptoms of Major Depressive Disorder (MDD). Total scores range from 0 (normal) to 22 (severe).	Baseline to Weeks 1, 2, 3, 4, 6, 8
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline	Measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).	Baseline to Weeks 1, 2, 3, 4, 6, 8
Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6)	Changes in Montgomery-Åsberg Depression Rating Scale (MADRS) and 6-Item Hamilton Depression Scale (HAMD-6) total scores were evaluated following dose up-titration in those patients who did not achieve the minimum 50% response for primary endpoint. MADRS is a rating scale for severity of depressive mood symptoms. Total scores range from 0 (low severity of symptoms) to 60 (high severity of symptoms). The HAMD-6, derived by the sum of HAMD-17 items 1, 2, 7, 8, 10 and 13, evaluates "core" symptoms of Major Depressive Disorder (MDD). Total subscale scores range from 0 (normal) to 22 (severe).	4 to 8 weeks
Clinical Global Impression of Severity (CGI-S) Scores at Each Visit	Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).	Baseline, Weeks 1, 2, 3, 4, 6, 8
Clinical Global Impression of Improvement (CGI-I) at Each Visit	Measures clinician's perception of patient improvement at the time of assessment compared with the start of treatment. Scores range from 1 (very much better) to 7 (very much worse).	Weeks 1, 2, 3, 4, 6, 8
Patient Global Impression of Improvement (PGI-I) Score at Each Visit	A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse).	Weeks 1, 2, 3, 4, 6, 8
Hamilton Anxiety Scale (HAMA) Score at Baseline and Weeks 4 and 8	The HAMA scale measures anxiety symptoms accompanying Major Depressive Disorder (MDD). Each item of the 14-item HAMA was scored from 0 (not present) to 4 (very severe), with a resulting maximum total score of 56.	Baseline and Weeks 4 and 8
Percentage of Responders	Patients with reduction in MADRS score ≥50% after 4 weeks were to stay on previous dose of duloxetine. Those with reduction in MADRS <50% were to receive 120 mg for remaining 4 weeks of treatment (up-titration from 60 mg to 120 mg for those randomized to 60 mg, and addition of placebo to 120 mg dose for those randomized to 120 mg). However, 2/70 patients randomized to 60 mg and then up-titrated to 120 mg after 4 weeks had reduction in MADRS ≥50% after 4 weeks, and 3/64 patients randomized to 120 mg and then given placebo in addition after 4 weeks had reduction in MADRS ≥50% after 4 weeks.	4 to 8 weeks
Patients Reaching Remission	Major Depressive Disorder remission was defined as a total MADRS score ≤12 at Week 8.	Week 8
Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8	The RFL questionnaire is an instrument that evaluates patient's reasons for not committing suicide using a 6-point rating scale, where 1 is "not at all important" and 6 is "extremely important". The questionnaire required participants to rate how important each item would be for living, if suicide was contemplated. Mean scores could range from 0 to 6.	Baseline and Week 8
Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication	Number of participants using medication for anxiety and sleep disturbances.	over 8 weeks
Number of Patients With Potentially Clinically Significant Laboratory Findings	Laboratory results that were potentially clinically significant.	over 8 weeks
Discontinuations Due to Adverse Events (AE)	Listing of adverse events (AE) that led to treatment discontinuation (DC).	over 8 weeks
Number of Participants Experiencing High Values for Vital Signs at Any Time During the Study	Systolic and diastolic blood pressure and pulse rate were measured after 2 minutes rest in a supine position. High values were: diastolic blood pressure ≥90 mm Hg and increase from baseline of ≥10 mm Hg; systolic blood pressure ≥140 mm Hg and increase from baseline of ≥10 mm Hg; pulse rate ≥100 beats per minute (bpm) and an increase of ≥10 bpm from baseline.	over 8 weeks
Change From Baseline to Week 4 and Week 8 in Weight	Change in weight = Post-baseline visit minus baseline.	Baseline to Weeks 4 and 8

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Boehringer Ingelheim

Publications and helpful links

General Publications

• Brecht S, Desaiah D, Marechal ES, Santini AM, Podhorna J, Guelfi JD. Efficacy and safety of duloxetine 60 mg and 120 mg daily in patients hospitalized for severe depression: a double-blind randomized trial. J Clin Psychiatry. 2011 Aug;72(8):1086-94. doi: 10.4088/JCP.09m05723blu. Epub 2010 Sep 21.
• Demyttenaere K, Desaiah D, Raskin J, Cairns V, Brecht S. Suicidal thoughts and reasons for living in hospitalized patients with severe depression: post-hoc analyses of a double-blind randomized trial of duloxetine. Prim Care Companion CNS Disord. 2014;16(3):PCC.13m01591. doi: 10.4088/PCC.13m01591. Epub 2014 May 1.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: January 11, 2007
• First Submitted That Met QC Criteria: January 11, 2007
• First Posted (Estimate): January 15, 2007

Study Record Updates

• Last Update Posted (Estimate): July 26, 2011
• Last Update Submitted That Met QC Criteria: July 22, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Duloxetine Hydrochloride
• Other Study ID Numbers: 10614 (Other Identifier: CTEP); F1J-BI-HMES (Other Identifier: Eli Lilly and Company)