Mechanisms of Antidepressant Non-Response in Late-Life Depression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mechanisms of Antidepressant Non-Response in Late-Life Depression (NCT01931202), a randomized na study. The primary outcome is Hamilton Rating Scale for Depression (HRSD).

2. Clinical Question

The record therefore presents a mechanistic rationale alongside a baseline symptom measure. The stated question about how executive function, brain imaging findings, and expectancy might relate to antidepressant response is not answered by the posted baseline HRSD summaries alone.

3. Trial Design

The study is recorded as randomized, quadruple masked, and parallel group, with a phase listed as NA. Its status is completed. The registry lists an enrollment of 138 and gives the dates 2014-02-19 for study start and 2019-01-17 for primary completion. The sponsor is New York State Psychiatric Institute.

Three arms are described: Double Blind-Placebo, Double Blind-Escitalopram, and Open Treatment With Escitalopram. The posted baseline HRSD data include 8 participants in the placebo arm, 51 in the blinded escitalopram arm, and 49 in the open-treatment escitalopram arm. These arm counts do not account for the enrollment figure on their own; the reason for the difference is not reported in the registry record.

The placebo arm description specifies one pill a day, increasing to 2 pills a day at week 4 if the patient had not remitted. The blinded escitalopram arm specifies 10mg, increasing to 20mg at week 4 if depression had not remitted. The open-treatment arm specifies the same escitalopram dose progression. Further details about randomization procedures, allocation concealment, masking roles, treatment adherence, or the timing of outcome assessments beyond the stated baseline primary measure are not reported in the registry record.

The primary outcome record is a continuous HRSD measure at baseline, summarized by a mean and standard deviation for each arm. No post-baseline primary outcome values or treatment comparisons are reported in the registry record. The design information alone does not establish what analyses were performed or how the broader mechanistic hypotheses were evaluated.

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.

Before assignment: 138 subjects signed consent, 108 were randomized to one of the 3 arms therefore they cannot be classified to any of the below arms.

Overall Study

Reasons for not completing this period:

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.

Population: Although 138 subjects were enrolled (signed consent), only 108 were randomized and included in analysis.

6. Primary Endpoint

The registry lists the primary outcome as Hamilton Rating Scale for Depression (HRSD), measured over Baseline.

The primary outcome is the Hamilton Rating Scale for Depression (HRSD), recorded at baseline and expressed in units on a scale. The registry describes it as a 24-item questionnaire used to indicate depression and guide evaluation of recovery. Its total scores range from 0-74, not including the atypical symptoms sub-scale. The record says a score of 16 or above is typically considered to indicate depressive symptoms, and higher scores indicate greater severity.

A continuous symptom scale can describe the level and spread of symptom scores across participants. For this outcome, the registry reports each arm's mean and standard deviation. The mean describes the group average; the standard deviation describes how dispersed individual scores are around that average. These summaries can characterize baseline symptom burden, but they do not by themselves show change during treatment or a treatment effect.

The use of HRSD is consistent with the study's focus on depression and possible differences in response mechanisms. However, the specified timeframe is baseline, rather than a stated post-treatment assessment. The registry record does not report a baseline-adjusted or follow-up HRSD analysis, a threshold-based response outcome, or a remission comparison. Thus, the posted primary outcome values characterize baseline scores only; they cannot establish whether scores changed after treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: HRSD scores are numerical values on a scale, and the registry specifies a mean and standard deviation as its summary statistics. A mean is the arithmetic average within an arm. A standard deviation describes how much individual observations vary around that average. It is not the standard error and does not directly quantify how precisely the mean has been estimated. Precision depends on both variability and the number of observations, along with the assumptions of the analysis.

What can a baseline mean show?

A baseline mean describes the average score before the treatment period represented by that assessment. In these data, each arm has a mean and a standard deviation, but no baseline comparison test or confidence interval is posted. A descriptive difference between group means is not, on its own, evidence that treatment changed symptoms. To estimate a treatment effect, an analysis would ordinarily use an outcome measured after treatment, a change from baseline, or a model that accounts for baseline values. Which approach, if any, was used is not reported in the registry record.

As a general statistical concept, a confidence interval communicates the uncertainty around an estimate under a chosen model and assumptions. It can help distinguish an estimate's central value from the range of values compatible with the data and method. No confidence intervals for the primary outcome are reported in the registry record. Likewise, no p-values or test statistics for primary outcome comparisons are reported. The absence of these quantities means the posted summaries do not support a formal assessment of statistical evidence for differences between arms.

Why does the scale's distribution matter?

Analyses of continuous outcomes often use methods that model the mean and make assumptions about the residual distribution, independence, and variance. The registry record does not identify an analysis model or report diagnostic checks. General statistical guidance is that distributional assumptions should be considered for the particular outcome and data; summaries alone cannot show whether those assumptions hold. Over-dispersion is especially relevant to count outcomes, where observed variability can exceed that expected under a simple count model. HRSD is recorded as a continuous measure, so count-model over-dispersion is not the defining issue for the posted primary outcome.

The trial is described as randomized and parallel group, but the registry record does not report the randomization procedure, stratification factors, or analysis population. Nor does it describe whether the primary analysis was intended to follow assigned groups, include only participants with observed outcomes, or use another population definition. These details matter because exclusions and missing outcomes can affect both the interpretation and precision of an estimate.

How should the planning illustration be understood?

The registry record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Its intended effect is stated as a fraction of the observed effect. Such values are planning illustrations, not observed power and not results from the trial. They depend on the chosen effect and assumptions, and should not be mistaken for the actual enrollment rationale. The sample-size justification for the trial, including the effect size used in its original design, is not reported in the registry record.

The posted primary outcome is measured at baseline, and the registry record does not report a treatment-effect estimate from which a primary-outcome planning illustration could be interpreted as an observed treatment result. No interim analysis plan, stopping rule, model specification, covariate adjustment, or handling of repeated measures is reported in the registry record. The reported design and descriptive data do not fill in those missing analysis details.

What can the posted summaries support?

They support a description of baseline HRSD scores in each listed arm, using the recorded sample sizes, means, and standard deviations. They do not establish a post-treatment difference, a causal treatment effect, or the proposed mechanism involving expectancy, executive function, or imaging findings. Those questions require relevant measurements and analyses, which are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Double Blind-Placebo Group", "Double Blind-Escitalopram Group", "Open Treatment With Escitalopram")
n   <- c(8, 51, 49)
m   <- c(22.8, 23.6, 22.9)
sp  <- c(4.9, 6.1, 6.3)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Double Blind-Placebo Group  8  22.800  4.900  18.703  26.897
CARM  Double Blind-Escitalopram Group  51  23.600  6.100  21.884  25.316
CARM  Open Treatment With Escitalopram  49  22.900  6.300  21.090  24.710

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures and 12 posted secondary outcomes. Secondary measures named in the record include HRSD, QIDS-SR, Credibility and Expectancy Scale measures, and QIDS-SR expectancy. Some measure names appear more than once in the list. The record does not clarify the relationship between those entries, identify which analyses were confirmatory, or describe a hierarchy of outcomes.

Multiplicity arises when several outcomes or comparisons are tested, because the chance of at least one apparently notable result can increase across a collection of tests. As a general statistical principle, a prespecified testing strategy or adjustment can help address that issue. Whether an adjustment was planned or used is not reported in the registry record. The record reports zero analyses, so no inferential results or multiplicity strategy can be assessed from the posted analysis information.

Missing-data handling is also not reported in the registry record. The primary outcome's arm-level sample sizes are stated, but the registry does not explain whether those counts represent everyone randomized, everyone assessed at baseline, or a defined analysis population. It does not report missingness by visit, reasons for missing observations, imputation methods, sensitivity analyses, or how withdrawals were handled.

The registry does not identify an intention-to-treat, per-protocol, or other analysis population. That omission matters for a randomized study because the population used for analysis affects what comparison is being estimated. Without a defined population and an account of missing data, the posted baseline summaries cannot establish whether the analyzed participants represent all randomized participants or whether later outcomes were available for a comparable set of participants across arms.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: fall (3.9%), chest pain (2.0%).

The registry reports serious adverse events for the three arms. In the Double Blind-Placebo Group, 0 of 8 participants at risk were affected by a serious adverse event. In the Double Blind-Escitalopram Group, 2 of 51 were affected. In the Open Treatment With Escitalopram arm, 1 of 49 was affected. Deaths are reported as 0 in each arm.

For other adverse events, the registry reports 0 affected participants in each arm, with the same arm-specific numbers at risk: 8, 51, and 49. These are counts within the listed groups; they do not describe event duration, severity beyond the serious-event classification, or whether an event was considered related to treatment.

The record separately lists Fall at 3.9% and Chest Pain at 2.0% among the top serious-event terms. It does not identify an arm for either percentage or give further detail in the posted information. Those percentages should not be attributed to a particular treatment group based on the information in the registry record.

Adverse-event counts are descriptive safety data. The registry record does not report comparative statistical analyses, exposure-adjusted rates, or detailed event narratives. Small group counts also mean that the posted figures alone provide limited information about the range or frequency of possible events. They should be read as the reported counts and terms, not as a complete characterization of safety.

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

The posted primary outcome establishes that baseline HRSD scores were recorded and summarized in the three listed arms. It gives the mean and standard deviation for each arm and the number of participants contributing to those summaries. The means are descriptive measures of group-level symptom severity at baseline, using the registry's definition of the scale.

Those values do not show treatment response. The primary outcome timeframe is baseline, and no post-treatment HRSD result or between-arm treatment estimate is reported in the registry record. A randomized design does not convert baseline summaries into evidence about treatment effects. In particular, the posted values cannot establish whether escitalopram differed from placebo, whether open treatment differed from blinded treatment, or whether symptoms changed over time.

The study summary gives a mechanistic rationale involving executive dysfunction, white matter hyperintensities, and expectancy in late-life depression. The posted primary outcome values do not test those relationships. Although several secondary measures are listed, their results and corresponding analyses are not reported in the registry record. The recorded baseline HRSD summaries therefore cannot confirm or refute the proposed mechanisms.

The safety information reports serious adverse-event counts and deaths by arm, as well as zero affected participants for other adverse events. These counts describe what is entered in the registry record, but do not provide a formal comparative safety analysis or detailed event context. The serious-event terms are listed with percentages but without arm attribution.

Overall, the record supports a narrow descriptive reading of baseline symptom scores and the listed safety counts. It does not report the inferential results needed to determine treatment effects, precision of comparative estimates, or the relationship between the proposed mechanisms and outcomes. The study's completion status does not supply those missing results.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between a trial's scientific rationale and the outcomes actually available for statistical interpretation. The registry summary describes a hypothesis about late-life depression, executive dysfunction, white matter hyperintensities, and expectancy. The posted primary outcome, however, is baseline HRSD, summarized by arm. A compelling mechanistic rationale does not substitute for outcome data that test the mechanism or estimate treatment effects.

It also shows why a measure's timeframe is central to interpretation. HRSD is a recognized symptom measure in the record, and its scale description gives direction and context for interpreting higher scores. But a baseline score describes status at entry; it does not demonstrate response, remission, or change after an intervention. Researchers and readers need to distinguish the value of a measure from the question its timing can answer.

The record's combination of randomized design information and descriptive baseline data is a reminder that design labels and statistical results serve different roles. Randomization is intended to support fair comparisons, while a suitable outcome analysis is needed to estimate those comparisons. Without a reported analysis, the effect and its precision remain unquantified. The arm-level means and standard deviations cannot fill that gap.

Finally, transparent reporting of analysis populations, missing-data handling, multiplicity, and model choices is important for judging how robust an estimate may be. These details are not reported in the registry record. Their absence limits statistical interpretation even when the trial is marked completed and the main design features are listed.

15. 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 this trial's posted outcome is that the registered primary measure is HRSD at baseline. The record does not report a post-treatment primary outcome or an analysis of change. Consequently, the posted means and standard deviations cannot answer whether outcomes differed after treatment or whether any treatment contrast was estimated.

The registry gives an overall enrollment of 138, while the primary-outcome summaries list 8 participants in the placebo arm, 51 in the blinded escitalopram arm, and 49 in the open-treatment arm. The reason these figures differ is not reported in the registry record. The record also does not explain the analysis population behind the arm-level summaries or whether these counts reflect all randomized participants.

The record does not report eligibility criteria in detail, including a specific age threshold, nor does it describe recruitment, adherence, treatment exposure, or participant flow. It lists a quadruple-masked design and an open-treatment arm but does not specify which parties were masked in each arm or how masking related to the open treatment. This leaves important operational features unclear.

Further limitations are the lack of reported inferential analyses, confidence intervals, model details, adjustment strategy, missing-data methods, and multiplicity plan. Secondary measures are listed, but their results are not reported in the registry record. The serious adverse-event counts are available, but the record does not provide event narratives or identify the arm associated with the listed serious-event percentages. These omissions restrict both efficacy and safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Mechanisms of Antidepressant Non-Response in Late-Life Depression — NCT01931202.
• Registry record last updated 2020-07-02; status last verified 2020-06.
• Results first posted 2020-04-08.
• 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.

19. Record Summary

The registry record identifies NCT01931202 as a completed, randomized, parallel-group study sponsored by New York State Psychiatric Institute. It lists quadruple masking, phase NA, enrollment of 138, a start date of 2014-02-19, and primary completion on 2019-01-17. The condition is major depressive disorder.

Three arms are described: blinded placebo, blinded escitalopram, and open treatment with escitalopram. The primary outcome is baseline HRSD, summarized as a mean and standard deviation. The record lists 13 outcome measures and 12 posted secondary outcomes, but reports zero analyses. No primary treatment-effect analysis or secondary outcome results are reported in the registry record.

Serious adverse events affected 0 of 8 participants in the placebo arm, 2 of 51 in the blinded escitalopram arm, and 1 of 49 in the open-treatment arm; deaths are listed as 0 in all arms. Other adverse events are listed as affecting 0 participants in every arm. The posted results are therefore descriptive, rather than an inferential assessment of treatment effects.