Study of Placebo Without Deception Versus Standard Antidepressant for Major Depressive Disorder - Full Text View

Purpose

In recent years, there has been growing evidence that antidepressants are only marginally effective compared to placebo for mild to moderate depression. In other words, although many people improve when they take antidepressant medications, almost as many get better with placebo pills. One possible solution to this problem would be to give patients a trail of a placebo prior to giving them an antidepressant, however there are ethical issues with doing this deceptively. New evidence from other placebo-responsive disorders such as irritable bowel syndrome shows that people may benefit from placebos even if they know they are taking them. This study aims to determine whether giving placebos without deception to people with major depressive disorder followed by the option to switch to an antidepressant is an effective strategy. There will be 3 groups of subjects. The first group is a standard treatment arm and will receive duloxetine, an antidepressant. The second will be given a placebo with the option to switch to duloxetine if they do not improve. The third group will receive supportive clinical visits the option to switch to duloxetine if they do not improve. This design will allow us to determine whether a sequenced treatment of a placebo without deception and then the option to switch to an antidepressant is a viable strategy. It will also help us to determine to what degree the benefit comes from the ritual of receiving and taking the placebo tablet versus the benefit of visits with a doctor alone. The primary hypothesis is that there will be a less than 5% difference between response rates after 12 weeks in the sequenced placebo-then-antidepressant treatment group (both subjects who have remained on placebo as well as those who have switched to the antidepressant will be considered as one group) compared to the immediate antidepressant therapy group.

Condition	Intervention
Major Depressive Disorder	Drug: Duloxetine Drug: placebo Other: Study visits only


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized Trial of Sequenced Treatment Using Placebo Without Deception Followed by Open-Label Antidepressant Versus Immediate Open-Label Antidepressant Treatment for Major Depressive Disorder

Resource links provided by NLM:

MedlinePlus related topics: Antidepressants

Drug Information available for: Duloxetine Duloxetine hydrochloride

U.S. FDA Resources

Further study details as provided by Sunnybrook Health Sciences Centre:

Primary Outcome Measures:

>= 50% improvement in Montgomery-Asberg Depression Rating Scale (MADRS) Scores (MADRS Response) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

MADRS remission [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Credibility and Expectancy Scale (CES) [ Time Frame: Baseline ] [ Designated as safety issue: No ]


Enrollment:	1
Study Start Date:	August 2012
Study Completion Date:	November 2014
Primary Completion Date:	August 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Open-label duloxetine 12 week treatment with duloxetine	Drug: Duloxetine 30 mg daily x 1 week followed by 60 mg daily Other Name: cymbalta
Experimental: Open-label Placebo 4 weeks of open label placebo with option to continue or switch to duloxetine for remaining 8 weeks.	Drug: placebo small placebo capsule (30 mg duloxetine equivalent) x 1 week followed by 60 mg equivalent capsule daily
Experimental: Supportive clinical management 4 weeks of supportive clinical management visits with option to continue or switch to duloxetine for remaining 8 weeks.	Other: Study visits only Weekly visits x 4 weeks followed by visits every 2 weeks

Eligibility


Ages Eligible for Study:	18 Years to 65 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Provision of written informed consent
Diagnosis of major depressive disorder, currently depressed as determined by DSM-IV diagnostic criteria (confirmed using the MINI)
Both females and males, aged 18 to 65 years
Outpatient status
Female patients of childbearing potential must have a negative urine human chorionic gonadotropin (hCG) test at enrolment and must be taking or willing to take some acceptable form of birth control during the course of the study if they are or plan to be sexually active
A grade 8 English comprehension, the ability to understand and comply with the requirements of the study and capable of providing informed consent
17-item Hamilton Depression Rating Scale (HAM-D) score of 14-22 at screening and at baseline

Exclusion Criteria:

Diagnosis of a past hypomanic, manic or mixed state.
Current or past psychotic symptoms
Substance or alcohol dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria
Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrolment
Any pervasive developmental disorder (according to DSM-IV criteria)
Diagnosis of dementia (according to DSM-IV criteria)
Is at significant risk for suicide, as defined by a score of ≥ 2 on the suicide item of the MADRS, any suicidal ideation with intent or a plan within the 3 months prior to study entry or in the opinion of the investigator.
Any history of lifetime suicide attempts
Current treatment with an antidepressant medication
Treatment with an antipsychotic, mood stabilizer or other psychoactive medication within a period of 5 half-lives of the medication prior to baseline visit
Known intolerance, hypersensitivity or lack of response to duloxetine as judged by the investigator
A history of treatment resistant depression (defined as 2 or more failed lifetime trials of antidepressant medication as judged by the investigator)
Currently undergoing psychotherapy that was initiated within the past 3 months
Significant medical condition that would contraindicate the use of duloxetine or that is untreated and would need urgent attention (as determined by treating physician)
Medical conditions that would significantly affect absorption, distribution, metabolism, or excretion of duloxetine
Unstable or inadequately treated medical illness (e.g. congestive heart failure, angina pectoris, hypertension) as judged by the investigator
Any clinically significant deviation from the reference range in clinical laboratory test results as judged by the investigator
Pregnancy (or female of child-bearing age not using adequate contraception) or lactation
A positive β-hCG test at enrolment
Involvement in the planning and conduct of the study
Previous enrolment or randomisation of treatment in the present study
Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01650740

Locations


Canada, Ontario
Sunnybook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5

Sponsors and Collaborators

Sunnybrook Health Sciences Centre

More Information


Responsible Party:	Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier:	NCT01650740 History of Changes
Other Study ID Numbers:	081-2012
Study First Received:	July 24, 2012
Last Updated:	December 19, 2014
Health Authority:	Canada: Health Canada

Additional relevant MeSH terms:


Disease Depressive Disorder Depression Depressive Disorder, Major Pathologic Processes Mood Disorders Mental Disorders Behavioral Symptoms Antidepressive Agents Duloxetine Hydrochloride Psychotropic Drugs	Serotonin and Noradrenaline Reuptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Physiological Effects of Drugs Analgesics Sensory System Agents Peripheral Nervous System Agents Dopamine Agents

ClinicalTrials.gov processed this record on September 27, 2016