Major Depressive DisorderPhase 4NCT01919216
Placebo Effects in the Treatment of Depression: Cognitive and Neural Mechanisms
A Phase 4 study testing Citalopram in people with Major Depressive Disorder, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
Studies of the neural mechanisms underlying placebo effects in antidepressant clinical trials largely have been limited to demonstrating objective differences in brain activity between responders and non-responders to placebo. Read more about this study
- Who is it for?
- Ages 24 to 75 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Citalopram
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2010to Jun 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 75 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and women aged 24-75 years
- Diagnosed with Diagnostic and Statistical Manual of Mental Disorders (DSM) IV Major Depressive Disorder, nonpsychotic
- 24-item Hamilton Rating Scale for Depression (HRSD) score ≥ 16
- Willing to and capable of providing informed consent and complying with study procedures
- Subjects are right-handed
- Using appropriate contraceptive method if woman of child-bearing age
Who cannot join
- Current comorbid Axis I DSM IV disorder other than Nicotine Dependence, Adjustment Disorder, Panic Disorder, Generalized Anxiety Disorder, or Social Phobia
- Diagnosis of substance abuse or dependence (excluding Nicotine Dependence) within the past 12 months
- History of psychosis or psychotic disorder, mania or bipolar disorder
- Subject is considered to be at significant risk of suicide based on current mental status and recent history
- History of allergic or adverse reaction to citalopram, or nonresponse to adequate trial of citalopram (at least 4 weeks at dose of 40mg) or escitalopram (at least 4 weeks at dose of 20mg)
- Subject is considered based on history to be unlikely to respond to the single agent citalopram (i.e., subjects with treatment resistant depression)
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- Current treatment with psychotherapy
- Clinical Global Impression (CGI)-Severity score of 7 at baseline Clinical Interview
- Current or recent (within the past 4 weeks) treatment with any of the following: antidepressants, antipsychotics, mood stabilizers, isoniazid, glucocorticoids, opiates, centrally active antihypertensive drugs (e.g. clonidine, reserpine)
- Subject has metal in body or prior history working with metal fragments (e.g., as a machinist), tattoos, or unable to tolerate the scanning procedures (i.e., severe obesity, claustrophobia)
- Acute, severe, or unstable medical illness
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute
New York, New York, 10032
About this study
Studies of the neural mechanisms underlying placebo effects in antidepressant clinical trials largely have been limited to demonstrating objective differences in brain activity between responders and non-responders to placebo. This 8 week Placebo-controlled and Open groups study employs a novel antidepressant trial design with integrated functional magnetic resonance imaging (fMRI) to manipulate patient expectancy and examine its neural mediators.
Read the detailed description
The placebo effect represents a potent treatment for Major Depressive Disorder (MDD)-placebo response in acute randomized controlled trials (RCTs) of antidepressant medications averages 30%, and meta-analyses have estimated the proportion of medication response attributable to placebo to be 50-75%. Patient expectancy is the mechanism of placebo effects in antidepressant RCTs and has been positively associated with medication response. Determining how expectancy alters the course of MDD could lead to methods of optimizing placebo effects and improving the treatment of MDD. In addition, investigating the neurobiology of placebo effects has the potential to elucidate the pathophysiology of MDD and the mechanisms of action of antidepressant treatments. Brain regions implicated in expectancy and placebo effects comprise prefrontal cortical (PFC) areas, amygdala, insular cortex, rostral anterior cingulate cortex (rACC), and dopaminergic reward pathways in the striatum. Pathological decreases in PFC and striatal function, increases in limbic activity, and disordered connectivity between these regions have all been observed in MDD, and the rostral and dorsal ACC have been repeatedly linked to antidepressant treatment response.
Therefore, studying placebo effects offers a window into the functioning of the neural circuits that are disturbed in MDD and improve with effective treatment. The goals of this study are to determine whether expectancy affects the outcome of antidepressant pharmacotherapy and to investigate the neural mechanisms of expectancy effects. These will be accomplished by conducting a clinical trial randomizing adult outpatients with MDD to 8 weeks of treatment in high vs. low expectancy conditions. The high expectancy condition will be open administration of citalopram, while the low expectancy condition will be placebo-controlled administration of citalopram. The neural mechanisms of expectancy will be determined using functional Magnetic Resonance Imaging (fMRI) paradigms to investigate treatment activation differences in brain regions associated with placebo effects and MDD.
- Conditions
- Major Depressive Disorder
- Being tested
- Citalopram
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CitalopramDrug
Also called Celexa
| Study group | Role | What they receive |
|---|---|---|
| Open Track | Active comparator | Open treatment with 20mg of citalopram, increased to 40mg if depression has not remitted at week 4. Receives: Drug: Citalopram |
| Placebo Track | Placebo comparator | Blinded treatment with either citalopram 20mg or placebo, increased to citalopram 40mg or placebo at week 4 if depression has not remitted. Receives: Drug: Citalopram |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hamilton Rating Scale for Depression
The patient is rated by a clinician among 24 dimensions with a score on a 3 or 5 point scale. A score of 0-9 is considered to be normal. Score between 10-18 is considered as mild depression, Scores between 19-26 indicate moderate, scores between 27-34 indicate severe, and score between 35-75 indicate very severe depression.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2013 (estimated)
- Study startJan 2010
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Bret Rutherford, New York State Psychiatric Institute
- Investigators
- Bret R Rutherford, MD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01919216
- Sponsor's protocol ID
- 6038/6996R
- Other IDs
- K23MH085236
- Status last verified
- Feb 2020
- First submitted
- 5 Aug 2013
- Last updated
- 9 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Rutherford BR, Roose SP. A model of placebo response in antidepressant clinical trials. Am J Psychiatry. 2013 Jul;170(7):723-33. doi: 10.1176/appi.ajp.2012.12040474.
PubMed 23318413Zilcha-Mano S, Wang Z, Peterson BS, Wall MM, Chen Y, Wager TD, Brown PJ, Roose SP, Rutherford BR. Neural mechanisms of expectancy-based placebo effects in antidepressant clinical trials. J Psychiatr Res. 2019 Sep;116:19-25. doi: 10.1016/j.jpsychires.2019.05.023. Epub 2019 May 26.
PubMed 31176108
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Placebo Effects in the Treatment of Depression: Cognitive and Neural Mechanisms
- ClinicalTrials.gov ID
- NCT01919216
- Acronym / sponsor ID
- 6038/6996R
- Conditions
- Major Depressive Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Jan 2010 (actual)
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 8 Aug 2013 (estimated)
- Results
- Posted 5 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Studies of the neural mechanisms underlying placebo effects in antidepressant clinical trials largely have been limited to demonstrating objective differences in brain activity between responders and non-responders to placebo. This 8 week Placebo-controlled and Open groups study employs a novel antidepressant trial design with integrated functional magnetic resonance imaging (fMRI) to manipulate patient expectancy and examine its neural mediators.
Detailed description
The placebo effect represents a potent treatment for Major Depressive Disorder (MDD)-placebo response in acute randomized controlled trials (RCTs) of antidepressant medications averages 30%, and meta-analyses have estimated the proportion of medication response attributable to placebo to be 50-75%. Patient expectancy is the mechanism of placebo effects in antidepressant RCTs and has been positively associated with medication response. Determining how expectancy alters the course of MDD could lead to methods of optimizing placebo effects and improving the treatment of MDD. In addition, investigating the neurobiology of placebo effects has the potential to elucidate the pathophysiology of MDD and the mechanisms of action of antidepressant treatments. Brain regions implicated in expectancy and placebo effects comprise prefrontal cortical (PFC) areas, amygdala, insular cortex, rostral anterior cingulate cortex (rACC), and dopaminergic reward pathways in the striatum. Pathological decreases in PFC and striatal function, increases in limbic activity, and disordered connectivity between these regions have all been observed in MDD, and the rostral and dorsal ACC have been repeatedly linked to antidepressant treatment response.
Therefore, studying placebo effects offers a window into the functioning of the neural circuits that are disturbed in MDD and improve with effective treatment. The goals of this study are to determine whether expectancy affects the outcome of antidepressant pharmacotherapy and to investigate the neural mechanisms of expectancy effects. These will be accomplished by conducting a clinical trial randomizing adult outpatients with MDD to 8 weeks of treatment in high vs. low expectancy conditions. The high expectancy condition will be open administration of citalopram, while the low expectancy condition will be placebo-controlled administration of citalopram. The neural mechanisms of expectancy will be determined using functional Magnetic Resonance Imaging (fMRI) paradigms to investigate treatment activation differences in brain regions associated with placebo effects and MDD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Open Track | Active comparator | Drug: CitalopramOpen treatment with 20mg of citalopram, increased to 40mg if depression has not remitted at week 4. |
| Placebo Track | Placebo comparator | Drug: CitalopramBlinded treatment with either citalopram 20mg or placebo, increased to citalopram 40mg or placebo at week 4 if depression has not remitted. |
Who may qualify
- Ages
- 24 to 75 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Men and women aged 24-75 years
- Diagnosed with Diagnostic and Statistical Manual of Mental Disorders (DSM) IV Major Depressive Disorder, nonpsychotic
- 24-item Hamilton Rating Scale for Depression (HRSD) score ≥ 16
- Willing to and capable of providing informed consent and complying with study procedures
- Subjects are right-handed
Key exclusion criteria (11 listed)
- Current comorbid Axis I DSM IV disorder other than Nicotine Dependence, Adjustment Disorder, Panic Disorder, Generalized Anxiety Disorder, or Social Phobia
- Diagnosis of substance abuse or dependence (excluding Nicotine Dependence) within the past 12 months
- History of psychosis or psychotic disorder, mania or bipolar disorder
- Subject is considered to be at significant risk of suicide based on current mental status and recent history
- History of allergic or adverse reaction to citalopram, or nonresponse to adequate trial of citalopram (at least 4 weeks at dose of 40mg) or escitalopram (at least 4 weeks at dose of 20mg)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CitalopramAlso: Celexa | Drug | Open Track, Placebo Track |
Primary outcome
Hamilton Rating Scale for Depression
Time frame: 8 weeks
The patient is rated by a clinician among 24 dimensions with a score on a 3 or 5 point scale. A score of 0-9 is considered to be normal. Score between 10-18 is considered as mild depression, Scores between 19-26 indicate moderate, scores between 27-34 indicate severe, and score between 35-75 indicate very severe depression.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23318413Rutherford BR, Roose SP. A model of placebo response in antidepressant clinical trials. Am J Psychiatry. 2013 Jul;170(7):723-33. doi: 10.1176/appi.ajp.2012.12040474.
- Derived from this study: PubMed 31176108Zilcha-Mano S, Wang Z, Peterson BS, Wall MM, Chen Y, Wager TD, Brown PJ, Roose SP, Rutherford BR. Neural mechanisms of expectancy-based placebo effects in antidepressant clinical trials. J Psychiatr Res. 2019 Sep;116:19-25. doi: 10.1016/j.jpsychires.2019.05.023. Epub 2019 May 26.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bret R Rutherford, MD principal investigator
New York State Psychiatric Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Citalopram in people with Major Depressive Disorder, run by New York State Psychiatric Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hamilton Rating Scale for Depression (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01919216, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2020.