Brain Energy Metabolism in Individuals With Major Depressive Disorder Receiving Escitalopram: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Brain Energy Metabolism in Individuals With Major Depressive Disorder Receiving Escitalopram (NCT00183677), a na phase 4 study. The primary outcome is Responder and Remission Status (%), Based on the Depression Rating Scale Score.

2. Clinical Question

3. Trial Design

This was a completed Phase 4, single-group study sponsored by Massachusetts General Hospital. The registry lists a start date of 2003-07 and a primary completion date of 2009-06. Enrollment was 97. Participants received open-label escitalopram, and the record lists no masking and no randomized allocation. The study description says it evaluated changes in brain energy metabolism due to escitalopram treatment in people with major depressive disorder.

The primary outcome listed in the registry was responder and remission status based on the depression rating scale score, measured at Week 12. The record describes the Hamilton Depression Rating Scale, 17 items, as the measure of change in depression severity from baseline to endpoint. Its stated possible range is 0-52. A responder was defined as having a reduction greater than 50% from baseline to endpoint; remission was defined as a score below 8 at the Week 12 endpoint.

The registry reports 53 completers among the 97 enrolled patients and says that only completers were included in the primary outcome measure. It does not explain why participants did not complete the study or give details about the timing or reasons for withdrawal. The primary endpoint results themselves are not reported in the registry record.

Because this is a single-group, open-label study, the design can describe outcomes among participants receiving escitalopram but does not establish a randomized contrast with an untreated or alternative-treatment group. In particular, a before-and-after change within a group is not, by itself, a comparison that separates treatment-associated change from other influences over time. The registry record does not report a protocol, sample-size justification, interim analyses, or a detailed statistical analysis plan.

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

Analysis population for the primary outcome, as defined in the registry: 97 patients with MDD (42 Female) enrolled in the 12 week study, 53 patients (27 Female) completed. Only completers were included in the primary outcome measure.

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.

6. Primary Endpoint

The registry lists the primary outcome as Responder and Remission Status (%), Based on the Depression Rating Scale Score, measured over Measured at Week 12.

The primary endpoint concerns clinical response and remission at Week 12, classified using the Hamilton Depression Rating Scale, 17 items (HAMD-17). The scale is described as ranging from 0-52 and as measuring change in depression severity from baseline to endpoint. The response definition requires a reduction greater than 50% between those measurements. The remission definition uses an endpoint score below 8. These are distinct classifications: response is based on the amount of change from baseline, whereas remission is based on the endpoint score.

Such categories can make a continuous symptom measure easier to interpret in terms of the proportion of participants who cross a prespecified threshold. They also discard some information: participants with similar scores may fall on opposite sides of a cutoff, and the categories do not show the full distribution of scores or the magnitude of change for each participant. That is a general property of threshold-based outcomes, not a result specific to this study.

The registry’s outcome title refers to status as a percentage, while the outcome metadata describe the measure as a number of participants. The actual responder and remission results are not reported in the registry record, so the number or proportion meeting either definition cannot be described. The registry states that only the 53 completers were included in this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins by distinguishing the design from the outcome definition. This record describes a single-group study with open treatment and no randomized allocation. A single-group design can describe what happened among the participants studied, but it does not create a concurrent comparison against which to estimate a treatment contrast. That is a general design principle. The registry does not report a control arm or a randomized comparison for this study.

What does the endpoint classify?

The HAMD-17 endpoint uses two threshold-based classifications. A responder is defined by a reduction greater than 50% from baseline to endpoint. Remission is defined by an endpoint score below 8. Response uses change relative to baseline; remission uses the endpoint score alone. A participant could meet either definition, both definitions, or neither, depending on the two scores. The registry does not report the individual score data or the counts in these categories, so their overlap and frequency are not reported in the registry record.

Thresholds are useful when a study wants to report a clinically interpretable category, but categorization has a statistical cost: it compresses a range of scores into a yes-or-no status and can make nearby values appear different if they fall on opposite sides of a cutoff. Conversely, distinct score changes may receive the same classification. This general limitation does not invalidate a categorical endpoint; it means the category should be interpreted as the specific rule it defines, not as a complete description of the score distribution.

What can a single-group result establish?

In general, a baseline-to-endpoint change in one group is a within-participant or within-group description. It is not the same as a randomized between-group treatment effect. In the absence of a concurrent control group, changes could reflect treatment, natural variation over time, other events, or measurement conditions. This study is recorded as open-label, so masking cannot be assumed. The registry does not report a comparison design that would address these limitations.

Statistical significance, if it had been reported, would not by itself describe the size or practical meaning of an effect. A confidence interval generally gives a range of estimates compatible with the data and analysis assumptions; its width conveys precision. Neither a primary outcome estimate nor a confidence interval is reported in the registry record. A p-value is also not reported. It is therefore not possible to discuss statistical evidence against a null hypothesis for the primary endpoint.

How should sample-size illustrations be read?

Sample-size calculations are planning tools. The registry information describes planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. These are illustration assumptions, not a description of the original single-group study design. They should not be read as the trial’s own sample-size justification or as observed power. The record does not report the original study’s sample-size justification.

In general, a planning calculation estimates the number of participants that a hypothetical design would require under specified assumptions about the effect, variability, allocation, significance threshold, and desired power. If the assumed effect changes, the planning requirement can change substantially. An illustration based on a fraction of an observed effect is therefore conditional on that effect estimate and on the hypothetical design assumptions. The primary endpoint’s observed values are not reported in the registry record, so the effect used for any such illustration cannot be independently evaluated from the registry information summarized in this record.

Equal allocation between two arms and a normal approximation do not describe the study’s actual design: this trial is recorded as single group. A hypothetical two-arm planning scenario cannot be treated as if the trial had enrolled two arms. General concerns such as over-dispersion matter when outcomes vary more than a model assumes, because a model that understates variability can produce overly optimistic precision or planning requirements. The registry does not report an over-dispersion assessment for this study, and the primary endpoint is recorded as a count-based binary outcome rather than a reported numerical result.

What does the analysis population tell us?

The registry says that only completers were included in the primary outcome measure. This is a restriction to participants who completed the study, rather than a reported analysis of everyone enrolled. In general, results among completers can differ from results among all enrolled participants if completion is related to outcome or other participant characteristics. That possibility cannot be assessed from the counts alone. The reasons for noncompletion, missing outcome values, and any imputation or sensitivity analysis are not reported in the registry record.

The registry lists one outcome measure and zero analyses. That does not establish which statistical test would have been appropriate or performed; the analysis details are not reported in the registry record. With no endpoint values, no analysis result can be independently recalculated from the posted registry information. No recalculated estimate or sponsor analysis is described in this record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and zero analyses. It does not report a multiplicity strategy, an outcome hierarchy, or whether any interim analyses were planned or conducted. When a study evaluates multiple outcomes or performs repeated statistical tests, multiplicity can increase the chance of a false-positive finding unless the analysis plan accounts for it. That is a general statistical concern, not evidence that multiplicity affected this study. The record does not provide enough information to determine whether additional analyses were undertaken beyond the registry listing.

For the primary outcome, the registry explicitly says that only completers were included. It reports 97 enrolled patients and 53 completers, but does not report endpoint status for those who did not complete, reasons for noncompletion, or methods for handling missing measurements. The number of participants contributing to each responder or remission classification is not reported in the registry record. No imputation, sensitivity analysis, or missing-data assumption is described.

In general, restricting an analysis to completers can limit how well its findings represent everyone enrolled, especially when completion is associated with the outcome. An intention-to-treat analysis generally retains participants in their assigned groups, but this is a single-group study and the record does not state that such an analysis was used. It would be inappropriate to infer a missing-data method or analysis population beyond the explicit completer statement.

The absence of reported analysis details also means the registry record does not establish how baseline and endpoint scores were handled statistically or whether adjustments were made. These aspects are not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports 0 serious adverse events among 97 participants at risk in the open-label escitalopram group. It separately reports 45 participants with other adverse events among 97 at risk. These counts belong to different registry categories and should not be combined or treated as interchangeable. The serious adverse event terms are not reported in the registry record.

The counts are descriptive safety information for a single group. They do not compare escitalopram with placebo or another treatment, because the study has no randomized comparator. The record also does not give event-level details such as timing, severity beyond the serious-versus-other distinction, recurrence, or attribution. It does not report deaths as a numerical result; the death field is not populated in the registry information.

In general, adverse event counts depend on how events are defined, collected, and followed. A count of participants with an event is not necessarily the same as a count of all event occurrences. The registry’s figures should therefore be read as category-specific participant counts within this study, not as a comparative risk estimate or a complete account of every possible safety outcome.

12. What the Result Does, and Does Not, Mean

The registry record establishes that a completed, open-label, single-group study enrolled 97 patients with major depressive disorder and evaluated a Week 12 endpoint based on HAMD-17 response and remission definitions. It reports that 53 patients completed the 12 week study and that only completers were included in the primary outcome measure. It also reports safety counts within its serious and other adverse event categories.

The registry record does not report the primary endpoint values. Therefore, it does not establish how many completers met the response definition, how many met the remission definition, or how precisely either outcome was estimated. Without outcome estimates and uncertainty measures, the magnitude and precision of the endpoint findings cannot be characterized. The outcome definitions alone are not evidence of how participants actually fared.

The study’s design also defines the limits of interpretation. With no randomized comparison group and no masking, the record cannot support a direct estimate of how outcomes differed from an alternative treatment or from no treatment. A change in a single group, even if reported, would not by itself identify the cause of that change. This is a general limitation of uncontrolled before-and-after evidence.

The safety counts describe recorded participants within the registry categories; they do not establish a comparative safety profile. The record does not provide detailed event terms or the context needed for a comparative estimate. Likewise, planning illustrations do not convert this single-group study into a two-arm trial and do not indicate the study’s observed power. The record does not report its original sample-size justification.

In short, the available information supports a description of the trial’s design, endpoint rules, completion count, and recorded adverse event counts. It does not support a numerical efficacy interpretation of the primary endpoint or a causal comparison with another treatment.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why design and reporting must be considered alongside an endpoint definition. The registry gives clear thresholds for response and remission, but it does not report the numbers meeting those thresholds. Without endpoint values, readers cannot assess magnitude, precision, or the distribution of outcomes. A well-defined outcome is necessary for interpretation, but it cannot substitute for reported results.

The study also makes the distinction between within-group description and between-group comparison concrete. Participants received open treatment in a single group, without randomized allocation or masking. These features matter because an observed change over time, if available, would not by itself show how outcomes compare with another treatment or what would have happened without the intervention. Statistical methods cannot remove a design limitation that leaves the comparison unobserved.

Completion is another important part of the analysis description. The registry says 53 of the 97 enrolled patients completed the study and that only completers entered the primary outcome measure. Knowing who contributed to an analysis is essential for judging what population the result represents. The record does not explain noncompletion or describe missing-data methods, so the implications of the completer restriction cannot be resolved.

Finally, hypothetical planning calculations should be kept separate from the actual trial design. Illustrations based on two-arm assumptions may help readers understand how planning depends on effect assumptions, but they are not evidence of the design or power of this single-group study. This case underscores the value of reporting results, analysis populations, missing-data handling, and the planned statistical approach together.

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 primary limitation for interpreting the endpoint is that its numerical results are not reported in the registry record. Although response and remission are defined, the record does not give the counts of participants meeting either definition, an effect estimate, a confidence interval, or a p-value. As a result, the endpoint’s magnitude and precision cannot be evaluated.

The study is single group, open label, and has no randomized comparison. Any within-group change would not distinguish treatment-associated change from other influences over time. The registry does not report masking, a comparator arm, or a design feature that would support a controlled estimate of treatment effect.

Only completers were included in the primary outcome measure. The record reports enrollment of 97 and completion by 53, but does not describe the reasons for noncompletion, endpoint data among noncompleters, or how missing observations were handled. This prevents assessment of how the completer analysis might differ from outcomes among all enrolled participants.

The record does not report a protocol, sample-size justification, interim analyses, a detailed statistical plan, or a multiplicity strategy. Although the study description identifies brain energy metabolism as an aim, the listed primary endpoint is responder and remission status based on HAMD-17. Numerical results for that endpoint are unavailable in the registry record. The safety information is also limited to participant counts in serious and other adverse event categories, without serious event terms or event-level detail.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Brain Energy Metabolism in Individuals With Major Depressive Disorder Receiving Escitalopram — NCT00183677.
• Registry record last updated 2017-01-04; status last verified 2016-11.
• Results first posted 2017-01-04.
• 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.

18. Record Summary

NCT00183677 is a completed Phase 4, single-group, open-label study sponsored by Massachusetts General Hospital. The registry lists a start date of 2003-07, a primary completion date of 2009-06, and enrollment of 97 patients with major depressive disorder. Participants received escitalopram.

The primary outcome was responder and remission status based on HAMD-17 at Week 12. Response was defined as a reduction greater than 50% from baseline to endpoint; remission was defined as an endpoint score below 8. The registry reports that 53 patients completed the 12 week study and that only completers were included in the primary outcome measure. Numerical primary outcome results are not reported in the registry record.

The safety record lists 0 serious adverse events among 97 at risk and 45 participants with other adverse events among 97 at risk. There was no randomized comparator. The record lists one outcome measure and zero analyses.