This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Neurobiological Bases of Placebo Response in Major Depressive Disorder (NCT01787240), a randomized phase 4 study. The primary outcome is Feasibility.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01787240 |
| Phase | Phase 4 |
| Condition | Major Depressive Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
The study concerns adults with major depressive disorder and asks about the feasibility of randomizing eligible people, as well as whether brain chemicals are similar among people who improve while taking escitalopram and those who improve while taking placebo. The registry record describes escitalopram as a selective serotonin reuptake inhibitor and identifies the placebo as an inactive substance.
Population
People with major depressive disorder who were screened for participation. The record describes an enrollment of 20, but does not give further eligibility details or describe the characteristics of participants who enrolled.
Intervention
Escitalopram 10mg. The study summary describes the broader research question in terms of an SSRI and says some participants may complete Acute Tryptophan Depletion or undergo an MR-PET scan.
Comparator
Placebo. The registry describes randomization to escitalopram 10mg or placebo after screening and a baseline assessment.
Primary question
What percentage of screened eligible patients agree to be randomized? The registry labels this outcome “Feasibility” and says it is assessed before randomization at the screening visit. It does not report the observed percentage.
The neurobiological question is not the same as the primary feasibility outcome. The brief summary frames it around comparing brain chemicals among people who get better while taking the two assigned treatments. The record does not provide a definition of improvement, a reported comparison of brain chemicals, or a result for that research question.
3. Trial Design
The registry describes a randomized, double-blind, parallel-group, phase 4 study of escitalopram 10mg and placebo. The listed enrollment is 20. Massachusetts General Hospital is named as the sponsor. The recorded start is 2012-11, the primary completion date is 2016-08, and the status is terminated. No reason for termination is reported in the registry record.
According to the arm descriptions, participants had a screening visit and baseline assessment before randomization to escitalopram 10mg or placebo. The descriptions for the two arms use the same wording. The record does not specify the randomization sequence, allocation concealment, or the details of how masking was maintained. “Double” is the recorded masking designation, but the registry does not identify which parties were masked.
The study summary says that some participants may complete Acute Tryptophan Depletion, a procedure described as a way to study serotonin’s role in depression. It also says some participants may undergo magnetic resonance-positron emission tomography scanning. The record does not specify how participants were selected for either procedure, how many underwent them, or how their results were analyzed.
The listed primary outcome is feasibility, rather than a treatment-effect endpoint. The record also names “Effects of Acute Tryptophan Depletion on Mood” as a secondary outcome, with that wording appearing twice. It lists four outcome measures but does not provide enough detail to identify all measures or explain the relationship among them. No analysis is listed in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Placebo | Escitalopram 10mg |
|---|---|---|
| STARTED | 15 | 5 |
| COMPLETED | 10 | 4 |
| NOT COMPLETED | 5 | 1 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Placebo | Escitalopram 10mg | Total |
|---|---|---|---|---|
| Participants analysed | 15 | 5 | 20 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 15 | 5 | 20 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | Years | 32.6 (SD 14.10) | 33 (SD 11.64) | 32.7 (SD 13.23) |
| Sex: Female, Male: Female | Participants | 7 | 3 | 10 |
| Sex: Female, Male: Male | Participants | 8 | 2 | 10 |
| Region of Enrollment: United States | participants | 15 | 5 | 20 |
6. Primary Endpoint
The registry lists the primary outcome as Feasibility, measured over This would occur at the first study visit (screening)..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percent of eligible patients |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled “Feasibility” and is defined as the percentage of screened eligible patients who agree to be randomized. The registry says participants were assessed for this outcome before randomization and places the assessment at the first study visit, screening. It does not report the observed percentage, the count of eligible patients, or the count who agreed to randomization.
As a general statistical concept, a feasibility endpoint can describe whether recruitment and randomization are workable in the setting studied. It is distinct from an endpoint measuring whether treatment changes symptoms or another clinical outcome. In this study, the stated measure concerns agreement to enter randomization; it does not by itself measure improvement in depression or establish whether escitalopram and placebo differ in neurobiology.
To interpret a reported percentage, readers would ordinarily need its numerator and denominator and a clear account of how eligibility and agreement were defined. Those details and the result are not reported in the registry record. The record also does not explain whether any threshold for acceptable feasibility was set in advance. Therefore, the endpoint’s intended meaning is identifiable, but its observed value and the criteria for judging it are not.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study’s design and stated research aims, but it does not provide a reported result for the primary feasibility outcome. There is no registry result stating how many screened eligible patients agreed to randomization or what percentage that represented. The primary question therefore cannot be answered from the recorded outcome information.
The study’s broader scientific aim was to examine whether people who improve while taking an SSRI and people who improve while taking placebo have similar brain chemicals. The registry does not report a measure of improvement, a brain-chemical estimate, or a between-group analysis addressing that question. It also does not report results for Acute Tryptophan Depletion or MR-PET. The intended neurobiological comparison should not be mistaken for a finding.
The safety record includes group-level counts for serious and other adverse events, as well as a list of serious adverse-event terms and percentages. These are descriptive entries, not a reported statistical comparison of treatment groups. The registry gives no adjusted estimate, confidence interval, or hypothesis test for those entries. The information does not establish whether any observed difference is attributable to treatment.
The listed enrollment is 20, while the adverse-event record gives different numbers at risk for the two groups. Those group-specific counts should be read as recorded rather than reconstructed into an assumed analysis population. The registry does not explain why the at-risk counts differ or how they relate to participation in the optional procedures.
Statistical precision cannot be assessed for the primary research question because no outcome estimate or interval is reported. A confidence interval, in general, communicates the range of values compatible with data under a specified method; it is not a substitute for a missing outcome estimate. The registry record does not report such an interval for feasibility or the neurobiological comparison.
The status is terminated, but the record does not state why the study ended or whether termination affected recruitment, outcome collection, or analysis. No conclusion about treatment benefit, lack of benefit, or equivalence follows from the absence of results. What can be said is limited to the recorded design, outcome definitions, and adverse-event entries.
9. Statistical Methods Explained
The registry identifies a randomized, double-blind, parallel design. Randomization is intended, in general, to allocate participants by chance, reducing systematic differences between groups at assignment. A parallel design means participants are assigned to one study arm rather than being described as switching between the two listed arms. The registry record does not give enough detail to evaluate the randomization procedure or concealment of assignments.
What does double masking mean?
As a general concept, masking is intended to limit the influence of knowledge about assigned treatment on participant experience, clinical care, or outcome assessment. The record labels the study “double” masked but does not say which participants, researchers, assessors, or other personnel were masked. It also does not describe how the placebo was matched to escitalopram or whether masking was assessed.
What does the primary endpoint measure?
The endpoint is a percentage: screened eligible patients who agree to randomization. This is a recruitment-feasibility measure rather than a measure of clinical response. For a percentage to be interpretable, the population counted in its denominator and the events counted in its numerator must be clear. The registry defines the intended denominator in words, but does not report the counts or the resulting percentage. It also does not report how eligibility was operationalized or how agreement was documented.
What can the absence of an outcome estimate tell us?
A statistical comparison requires observed outcome data and a specified analysis. The registry lists no analyses and does not report a result for feasibility or the neurobiological question. Consequently, there is no reported effect estimate to interpret, no uncertainty interval to assess, and no hypothesis-test result to describe. This is different from a finding of no difference: an unreported comparison cannot establish similarity or difference.
How should the planning illustrations be understood?
General statistical context: sample-size planning asks how much information a future study would need to detect a chosen effect under stated assumptions. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a stated fraction of an observed effect. These are planning assumptions, not evidence that this trial used that design rationale. The registry does not report the trial’s own sample-size justification.
Planning illustrations are not observed power. Observed power is not a replacement for a confidence interval or an estimate of the result, and a planning calculation does not show what the trial found. The record does not provide a primary-outcome effect estimate to interpret, and the feasibility endpoint is not presented as a conventional treatment-effect comparison. Accordingly, planning scenarios cannot supply a missing result or establish whether the study was adequately sized for its aims.
Why does over-dispersion matter in general?
General statistical context: count outcomes are sometimes more variable than a simple model assumes. Over-dispersion means the observed variability exceeds the model’s expected variability. If it is ignored, standard errors may be too small and uncertainty may appear narrower than warranted. The registry record does not identify a count model, report an over-dispersion assessment, or describe a model for the listed outcomes. This general issue should not be read as a claim that over-dispersion occurred in this study.
What do the adverse-event counts represent statistically?
The safety record gives numbers at risk and numbers affected for serious and other adverse events by arm. These entries are descriptive counts. They do not, on their own, adjust for differences in time under observation, participant characteristics, or exposure to study procedures. The record does not explain those aspects of safety follow-up or report a comparative model. The listed percentages for serious-event terms also lack a stated denominator in the registry record, so they should be quoted as recorded rather than converted to counts.
Across these methods, the key distinction is between a planned design, a statistical assumption, and an observed result. The registry reports design features and an endpoint definition, but does not report the analysis details or primary outcome result needed for inferential conclusions.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a multiplicity plan. Multiplicity arises when several outcomes, comparisons, time points, or subgroup analyses are tested: without an appropriate plan, the chance of at least one apparently notable result can increase. This is general statistical context, not a claim about analyses conducted in this study.
The record names “Effects of Acute Tryptophan Depletion on Mood” twice among secondary outcomes and lists four outcome measures. It does not explain whether the repeated wording refers to separate measures, time points, or a duplicate entry. It also does not identify all outcome measures, designate a hierarchy among them, or describe any adjustment for multiple testing. No analysis is listed in the registry record.
Missing-data methods are not reported in the registry record. In general, interpretation depends on knowing how missing outcomes were handled, how much information was unavailable, and whether the reasons for missingness could be related to treatment or outcome. The registry does not give those details for feasibility, mood, imaging, or other measures.
Analysis populations are also not described. The record does not say whether any analysis was intended to include all randomized participants, only participants who completed specified procedures, or another defined group. Because some participants may complete Acute Tryptophan Depletion or undergo MR-PET, clear reporting of which participants contribute to each outcome would be important; the registry does not provide it.
No imputation approach, sensitivity analysis, prespecified subgroup plan, or interim-analysis plan is reported in the registry record. Their absence from the record does not establish whether they were used elsewhere; it means they cannot be evaluated from the registry information.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Placebo | 4 | 15 | 26.7% |
| Escitalopram 10mg | 2 | 5 | 40.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo | 0 of 15 |
| Escitalopram 10mg | 0 of 5 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo | 12 of 15 |
| Escitalopram 10mg | 1 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | Escitalopram 10mg |
|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | 0 of 15 | 1 of 5 |
| Chest pain | Cardiac disorders | 1 of 15 | 0 of 5 |
| Tinnitus | Ear and labyrinth disorders | 1 of 15 | 0 of 5 |
| Dry mouth | Gastrointestinal disorders | 1 of 15 | 0 of 5 |
| Upper respiratory infection | Infections and infestations | 0 of 15 | 1 of 5 |
| Pancreatitis/Influenza | Infections and infestations | 1 of 15 | 0 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | Escitalopram 10mg |
|---|---|---|---|
| Headache | Nervous system disorders | 3 of 15 | 1 of 5 |
| Nausea | Gastrointestinal disorders | 4 of 15 | 0 of 5 |
| Diarrhea | Gastrointestinal disorders | 2 of 15 | 1 of 5 |
| Anxiety attack | Psychiatric disorders | 3 of 15 | 0 of 5 |
| Insomnia | Nervous system disorders | 2 of 15 | 0 of 5 |
| Constipation | Gastrointestinal disorders | 2 of 15 | 0 of 5 |
| Irritability | Psychiatric disorders | 2 of 15 | 0 of 5 |
| Gas/irregular Bowels | Gastrointestinal disorders | 1 of 15 | 0 of 5 |
| Sleep paralysis | Nervous system disorders | 1 of 15 | 0 of 5 |
| Hypotension | Vascular disorders | 1 of 15 | 0 of 5 |
Serious events with the highest arm-level rate: diarrhea (20.0%), upper respiratory infection (20.0%), chest pain (6.7%), tinnitus (6.7%), dry mouth (6.7%).
The registry records serious adverse events for the placebo group as 15 at risk and 4 affected, and for the escitalopram 10mg group as 5 at risk and 2 affected. For other adverse events, it records 15 at risk and 12 affected in the placebo group, and 5 at risk and 1 affected in the escitalopram 10mg group. Deaths are recorded as 0 in each group.
These are descriptive counts, not a formal comparison. The registry does not report a statistical test, adjusted estimate, confidence interval, or explanation for the group-specific numbers at risk. The counts should not be treated as evidence that a treatment caused or prevented an event.
The serious adverse-event terms listed include Diarrhea and Upper respiratory infection, each at 20.0%; Chest pain, Tinnitus, Dry mouth, and Pancreatitis/Influenza, each at 6.7%. The record does not state the denominator for these percentages or assign the terms to a particular arm. They should therefore be read as registry-listed terms and percentages, not as arm-specific rates.
The registry does not describe event timing, duration, severity grading beyond the serious-event classification, or the relationship of events to treatment. The safety entries alone cannot establish comparative risk.
12. What the Result Does, and Does Not, Mean
The record documents a randomized, double-blind study of escitalopram 10mg versus placebo in major depressive disorder, with a primary endpoint focused on feasibility. It also describes a broader interest in neurobiological similarities among people who improve while taking an SSRI or placebo. Those are the aims and design, not evidence that the primary endpoint was met or that a neurobiological similarity was observed.
The primary feasibility result is not reported in the registry record. There is no stated percentage of eligible screened patients who agreed to randomization and no associated uncertainty estimate. The record therefore does not establish how feasible recruitment was according to the study’s own outcome definition.
Likewise, no result is reported for the brain-chemical question, Acute Tryptophan Depletion, or MR-PET. Without outcome estimates and analysis details, it is not possible to determine whether the groups differed, whether they were similar, or how precise any estimate might have been. Missing results are not evidence of no effect or equivalence.
The adverse-event counts and listed terms describe what the registry records, but they do not establish a causal relationship or provide a controlled statistical comparison. The group-specific numbers at risk and the unspecified denominator for the listed percentages limit interpretation of those entries.
In general, a randomized design can support a comparative inference when outcomes are reported and the analysis is appropriate to the design. Here, the registry information supports description of the planned comparison and the recorded safety entries, but not a conclusion about treatment efficacy, neurobiological mechanism, or comparative safety. The terminated status is recorded, but the reason and its implications for the data are not reported.
13. Why This Trial Matters Statistically
This study is statistically notable because its primary endpoint concerns feasibility rather than a direct treatment-effect estimate. The question—what percentage of eligible people agree to randomization—addresses whether a research design can recruit participants willing to enter a randomized comparison. That question is distinct from whether either assigned treatment changes depression symptoms or brain measures.
The distinction matters because feasibility evidence can inform whether a study process is workable, while clinical and neurobiological conclusions require their own outcomes and analyses. The registry defines the feasibility measure but does not report its result. It also describes a neurobiological aim but does not report the measurements or comparison needed to address it.
The study combines a medication comparison with optional procedures involving Acute Tryptophan Depletion and MR-PET for some participants. Such a design raises a general reporting need to clarify which participants contribute to which outcomes and how procedure-related data are analyzed. Those details are not reported in the registry record.
The adverse-event entries also illustrate why raw counts should be separated from comparative inference. Group counts, percentages without a stated denominator, and no reported analysis can describe the record, but they do not quantify a treatment effect with precision or resolve causal attribution.
Finally, a terminated status without a reported reason makes outcome completeness difficult to assess. Clear results for the primary feasibility endpoint, an account of missing outcomes, and analyses aligned with the separate feasibility and neurobiological aims would be needed to support stronger conclusions.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpreting this trial is that the registry record does not report the primary feasibility result. Although the outcome definition identifies the intended percentage, it provides neither the underlying counts nor the observed value. No conclusion about recruitment feasibility can therefore be drawn from the recorded outcome information.
The registry also does not report results for the study’s neurobiological aim, Acute Tryptophan Depletion, or MR-PET. The brief summary says some participants may undergo these procedures, but does not state who did so, how outcomes were measured, or how the resulting data were analyzed. The secondary outcome wording is repeated and the full set of four outcome measures is not explained.
The enrollment is listed as 20, and the study status is terminated. The reason for termination, recruitment progress, and completeness of follow-up are not reported. The safety entries give different numbers at risk by arm, but the record does not explain the basis for those counts or their relationship to the listed enrollment. No assumption about why they differ is warranted.
Important methods are also absent from the registry record: the randomization procedure, masking details, analysis populations, missing-data handling, multiplicity plan, and sample-size justification. The record does not report an outcome estimate, confidence interval, or hypothesis test for the primary question. These gaps prevent assessment of statistical precision, robustness, and the extent to which the stated aims were addressed.
Finally, adverse-event percentages are listed without a stated denominator or arm assignment for the event terms. Their descriptive value is limited, and they should not be interpreted as comparative rates.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Neurobiological Bases of Placebo Response in Major Depressive Disorder — NCT01787240.
- Registry record last updated 2017-05-16; status last verified 2017-04.
- Results first posted 2017-04-14.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01787240 is a phase 4, randomized, double-blind, parallel study titled “Neurobiological Bases of Placebo Response in Major Depressive Disorder.” Massachusetts General Hospital is the sponsor. Major depressive disorder is the listed condition, and enrollment is recorded as 20.
The study compares escitalopram 10mg with placebo. Its primary outcome is feasibility, defined as the percentage of screened eligible patients who agree to be randomized at screening. The summary also describes a neurobiological research aim and says some participants may complete Acute Tryptophan Depletion or undergo MR-PET.
The recorded start is 2012-11, primary completion is 2016-08, and status is terminated. The registry record does not report the primary feasibility result, results for the neurobiological question, analysis details, or a reason for termination. Safety entries are recorded by arm, but no comparative safety analysis is reported.