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 Influence of Escitalopram on Fear Conditioning (NCT01398514), a randomized phase 4 study. The primary outcome is Physiological Reactivity as Measured by Square-root Transformed Skin Conductance Conditioned Response in Early Extinction Trials 1 to 4.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01398514 |
| Phase | Phase 4 |
| Condition | Fear Conditioning |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 65 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
The registry record identifies fear conditioning as the condition under study and describes participants undergoing a fear-conditioning paradigm. Eligibility criteria, participant characteristics, recruitment setting, and other details defining the study population are not reported in the registry record. The enrollment recorded for the trial is 65.
Intervention
The active-medication group received escitalopram 10mg/day. The study description says the medication was initiated before the fear-conditioning assessment. The primary outcome timeframe is Day 2 of the paradigm, described as 15 to 18 days post medication initiation. Adherence, dose changes, and the exact treatment duration are not reported in the registry record.
Comparator
The comparison group received a matched pill placebo. The registry record describes randomized assignment, double masking, and a parallel-group model. It does not report the allocation ratio or identify which people were masked. The active and placebo groups are compared on the primary physiological outcome.
Primary question
The primary question is whether group, conditioned-stimulus type, and early-extinction trial jointly relate to square-root transformed skin conductance conditioned response during trials 1 to 4. The CS+ was associated with the unconditioned stimulus, an electric shock; the CS- was not. The registry record specifies a three-way interaction, rather than a single comparison of group averages. The numerical result for that interaction is not reported in the registry record.
3. Trial Design
The registry record describes a randomized, double-masked, parallel-group phase 4 trial sponsored by Massachusetts General Hospital. Escitalopram was compared with matched pill placebo. The active-medication arm is described as escitalopram 10mg/day. Enrollment is recorded as 65, and the trial status is completed. The record lists Fear Conditioning as the condition under study.
The trial start is recorded as 2008-10, with primary completion recorded as 2011-06. These dates describe the registry timeline; they do not give the dates on which individual participants were treated or assessed. The primary outcome timeframe is Day 2 of the fear-conditioning paradigm, 15 to 18 days post medication initiation.
Randomization is intended, in general, to reduce systematic differences between groups at assignment. Double masking can, in general, reduce the influence of treatment knowledge on participant experience or outcome assessment. The record does not identify who was masked, describe how the random sequence was generated or concealed, or report whether masking was maintained. The actual allocation ratio is not reported in the registry record. Equal allocation appears as an assumption for planning illustrations, not as a description of the observed assignment process.
A parallel-group design assigns participants to a group that receives the assigned intervention or comparator rather than describing a crossover. Details of treatment adherence, withdrawals, follow-up beyond the primary assessment, and the number included in the primary analysis are not reported in the registry record. The registry lists two outcome measures, but details and numerical results beyond the primary outcome are not reported 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.
Before assignment: 65 participants signed consent and were screened for enrollment. 10 participants did not meet study entry criteria due to exclusionary psychiatric conditions. Of the 55 eligible participants, 3 withdrew and 1 was lost to follow up. 52 participants were randomly assigned to a treatment arm. Fourteen were excluded from analyses.
Overall Study
| Stage | Active Medication | Placebo |
|---|---|---|
| STARTED | 26 | 26 |
| COMPLETED | 18 | 20 |
| NOT COMPLETED | 8 | 6 |
Reasons for not completing this period:
| Reason | Active Medication | Placebo |
|---|---|---|
| Adverse Event | 1 | 0 |
| Non-compliance with study procedures | 2 | 0 |
| Physiologic non-responsiveness | 1 | 3 |
| Failure to show a conditioned response | 4 | 3 |
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 | Active Medication | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 26 | 26 | 52 | |
| Age, Categorical: <=18 years | Participants | 1 | 0 | 1 |
| Age, Categorical: Between 18 and 65 years | Participants | 25 | 26 | 51 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 34.04 (SD 11.56) | 30.46 (SD 11.46) | 32.25 (SD 11.54) |
| Sex: Female, Male: Female | Participants | 14 | 12 | 26 |
| Sex: Female, Male: Male | Participants | 12 | 14 | 26 |
| Region of Enrollment: United States | participants | 26 | 26 | 52 |
6. Primary Endpoint
The registry lists the primary outcome as Physiological Reactivity as Measured by Square-root Transformed Skin Conductance Conditioned Response in Early Extinction Trials 1 to 4, measured over Day 2 of Fear Conditioning Paradigm (15 to 18 days post medication initiation).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | micro-Siemens (square rooted) |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the mean square-root transformed skin conductance conditioned response during trials 1 to 4 of the Early Extinction Phase. Its stated unit is micro-Siemens (square rooted), and the registry identifies standard error as the dispersion measure. The timeframe is Day 2 of the Fear Conditioning Paradigm, 15 to 18 days post medication initiation.
Skin conductance is a physiological response. In this experiment, the CS+ denotes the conditioned stimulus associated with the unconditioned stimulus, an electric shock; the CS- denotes a stimulus not associated with that unconditioned stimulus. The registry states that higher values reflect higher skin conductance response for either stimulus. The outcome therefore describes physiological responding to the stimuli, not a direct report of subjective fear, anxiety, or distress.
In general, measuring skin conductance can provide a physiological index of conditioned responding during a learning task. A square-root transformation changes the scale on which the measure is analyzed and reported; the reason for choosing that transformation is not reported in the registry record. The endpoint focuses on early extinction trials, when responses are observed after the conditioning phase. Its primary question concerns the joint pattern across group, CS type, and trial, rather than only the average response in either group. Numerical means, standard errors, and an inferential result for the primary endpoint are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary outcome is defined as a three-way interaction between group, CS type, and trials 1 to 4. In general, such an interaction asks whether the pattern across trials for CS+ relative to CS- differs between the active-medication and placebo groups. It is not equivalent to asking only whether the overall mean differs between groups. The interpretation depends on the estimated interaction and its uncertainty, neither of which is reported in the registry record.
The registry describes the outcome as a mean of a continuous measure and identifies standard error as its dispersion measure. However, it does not report the group means, standard errors, interaction estimate, confidence interval, or p-value for the primary outcome. Consequently, the direction and magnitude of the observed pattern, and how precisely it was estimated, cannot be assessed from the registry record. No conclusion about a between-group difference or its absence can be drawn from the endpoint description alone.
The outcome definition distinguishes CS+ from CS- and specifies higher values as greater skin conductance response to either stimulus. An interaction could reflect differences involving the CS+ response, the CS- response, the change across early extinction trials, or their combined pattern. Without the fitted estimate and suitable supporting summaries, the registry record does not show which component contributes to any group pattern. It also does not report whether the analysis used a particular contrast, model, or adjustment.
The registry records enrollment as 65, but enrollment is not the same as the number contributing data to the primary analysis. The analyzed population and the number with outcome measurements are not reported in the registry record. Nor are missing measurements, exclusions, withdrawals, or the handling of incomplete trial data described. These details matter because the available data and analysis population determine what the estimated group pattern represents.
The registry record reports no analysis entries. That absence should be read as a reporting limitation, not as evidence that investigators performed no analyses. The sample-size assumptions describe planning illustrations based on an observed effect, with two-sided significance level 0.05, equal allocation between arms, and a normal approximation. Numerical planning results and the observed effect used for those illustrations are not reported in the registry record. Such illustrations would be planning quantities, not observed power or a substitute for the primary estimate and its uncertainty.
Safety information is also limited to event counts in the record. Serious adverse events are recorded as zero in each group, while other adverse events are recorded as affecting 13 in the active-medication group and 7 in the placebo group. These figures describe the posted safety counts; they do not supply the missing primary outcome result and do not establish the cause of any event.
9. Statistical Methods Explained
The registry record names the primary outcome and its intended summary but does not report the statistical analysis plan or the numerical primary result. The explanations below are general descriptions of the statistical ideas relevant to the endpoint, not claims about the methods actually used by the investigators.
What does the three-way interaction ask?
The endpoint involves three factors: group (active medication or placebo), conditioned-stimulus type (CS+ or CS-), and trial (trials 1 to 4). In general, an interaction describes whether the association between one factor and the outcome changes across levels of another factor. A three-way interaction asks whether the relationship between stimulus type and trial differs by group. Put another way, it tests whether the pattern of responses across early extinction trials, comparing CS+ with CS-, differs between groups.
This question is more specific than a test of whether the groups have different overall averages. It is also more specific than a test of whether CS+ and CS- responses differ on average, or whether responses change over trials without regard to stimulus type. A result for the interaction would need to be interpreted alongside estimates for the relevant group, stimulus, and trial patterns. Those estimates and the interaction result are not reported in the registry record.
What does a mean and standard error describe?
The registry identifies the parameter as a mean and the dispersion as standard error. In general, a mean describes the central level of a continuous measurement in the analyzed data. A standard error describes the statistical uncertainty around an estimated quantity, such as a mean; it is not the spread of individual observations. A confidence interval combines an estimate with an uncertainty range and can help readers judge the precision and plausible values consistent with the data under the analysis. The registry record does not report means, standard errors, or confidence intervals for the primary endpoint.
The endpoint is square-root transformed. In general, transforming a measurement changes the scale and can affect its distribution and the interpretation of model estimates. A result on a transformed scale is not automatically a result on the original measurement scale. The registry record does not state why this transformation was selected, whether results were also presented on the original scale, or how any estimates were translated for interpretation.
Why can repeated measurements matter?
The primary endpoint refers to multiple trials, and the description gives results across CS types. In general, measurements from the same participant can be related rather than independent. A statistical analysis may need to account for that relationship when estimating uncertainty. Treating related observations as independent when they are not can make uncertainty estimates misleading. The method used to account for within-participant dependence, if any, is not reported in the registry record.
Over-dispersion is a general concern when observed variability is greater than a model assumes. If a model understates variability, its standard errors may be too small and its inferential conclusions too confident. The appropriate variance structure depends on the data and analysis. The registry record does not provide model diagnostics, variance assumptions, or information about over-dispersion, so it is not possible to assess whether this issue arose or how it was handled.
What can randomization and masking contribute?
In general, random assignment can help balance measured and unmeasured characteristics between groups on average, while masking can limit some influences of treatment knowledge. These design features do not by themselves guarantee balanced groups in a particular trial or prevent bias from missing outcomes, deviations from assigned treatment, or measurement procedures. The registry identifies the study as randomized and double-masked but does not report sequence generation, allocation concealment, masking procedures, or checks on masking. The allocation ratio used in practice is not reported in the registry record.
What is known about planning and inference?
The record describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It also states that the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that a particular number of participants was enrolled for a specific power target. Numerical planning results and the observed effect underlying them are not reported in the registry record. A planning illustration is not observed power, and it cannot replace the reported estimate and uncertainty for the trial outcome.
The registry record does not report the test statistic, degrees of freedom, model formula, covariates, handling of baseline measurements, or the rule used to determine statistical significance for the primary analysis. It also does not report whether analyses were adjusted for other factors or whether sensitivity analyses were conducted. No recalculated estimate is available from the posted summary statistics. Therefore, there is no basis in the registry record for comparing a recalculation with a sponsor analysis or deciding that one should take precedence.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists two outcome measures and zero analysis entries. The primary outcome is described, but numerical results for it are not reported in the registry record. Details and results for the other outcome measure are also not reported in the registry record. The absence of analysis entries does not establish that no analyses were performed; it means the registry record does not document them in the listed analysis records.
Multiplicity arises when several outcomes, contrasts, or analyses are considered. In general, repeated testing can increase the chance of obtaining a nominally notable result even when there is no underlying effect. A statistical plan may specify a primary comparison, an order of testing, or an adjustment for multiple tests. The registry record does not report a multiplicity strategy, planned contrasts, or how the two outcome measures relate to the primary question. It is therefore not possible to determine how multiplicity was handled.
Missing-data methods and analysis populations are not reported in the registry record. The enrollment count does not establish how many participants contributed to each outcome or trial, and the safety counts do not provide that information for the primary endpoint. The record does not describe withdrawals, missing trial measurements, exclusions, imputation, or sensitivity analyses. In general, missingness can affect both the amount of information available and the interpretation of an estimate, especially if the chance of missing data relates to participants' responses. Without a description of missingness and its handling, the impact on the primary result cannot be assessed.
The registry record also does not identify whether the primary analysis followed assignment regardless of treatment received, included only participants meeting specified criteria, or used another analysis population. Those choices can answer different questions. No particular analysis population or missing-data procedure should be inferred from the design description alone.
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 |
|---|---|---|---|
| Active Medication | 0 | 25 | 0.0% |
| Placebo | 0 | 26 | 0.0% |
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 |
|---|---|
| Active Medication | 13 of 25 |
| Placebo | 7 of 26 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Active Medication | Placebo |
|---|---|---|---|
| Headache | Nervous system disorders | 3 of 25 | 1 of 26 |
| Jitteriness / Restlessness | Nervous system disorders | 1 of 25 | 2 of 26 |
| Sedation / Drowsiness | General disorders | 3 of 25 | 0 of 26 |
| Insomnia | General disorders | 3 of 25 | 0 of 26 |
| Appetite decrease | Gastrointestinal disorders | 2 of 25 | 0 of 26 |
| Anxiety / Nervousness | Psychiatric disorders | 2 of 25 | 0 of 26 |
| Vivid or Disturbing Dreams | General disorders | 1 of 25 | 1 of 26 |
| Sexual Dysfunction | Reproductive system and breast disorders | 2 of 25 | 0 of 26 |
| Tremor / Shakiness | Nervous system disorders | 1 of 25 | 0 of 26 |
| Fatigue | General disorders | 1 of 25 | 0 of 26 |
The registry records zero serious adverse events among 25 at risk in the active-medication group and zero among 26 at risk in the placebo group. Other adverse events are recorded as affecting 13 among 25 at risk in the active-medication group and 7 among 26 at risk in the placebo group. These are the counts recorded for the respective safety categories; they are not the primary physiological outcome.
The zero serious-event counts mean that no serious adverse events are recorded as affecting participants in either group in this summary. They do not establish that serious events cannot occur or that the risk is absent. In general, an event count is interpreted in relation to how safety was defined, how long participants were observed, how events were collected, and how completely they were reported. Those details are not reported in the registry record. The serious adverse event terms are not reported in the registry record, and deaths are not reported in the registry record.
The other adverse-event counts do not by themselves show whether an event was caused by the assigned treatment. Event definitions, severity, timing, individual event types, and how many participants had more than one event are not reported in the registry record. The counts should therefore be read as a limited descriptive safety summary, not as a causal comparison or a complete characterization of safety.
12. What the Result Does, and Does Not, Mean
The registry record defines a focused experimental question: whether group, conditioned-stimulus type, and early-extinction trial jointly relate to square-root transformed skin conductance conditioned response. This is a physiological outcome within a fear-conditioning paradigm. It is not, by itself, a direct measure of a clinical diagnosis, long-term symptoms, or an individual participant's experience of anxiety.
The numerical result for the primary interaction is not reported in the registry record. Without an estimate and a measure of uncertainty, the posted information does not establish the direction, size, or precision of the observed pattern. It does not support a conclusion that escitalopram changed the primary outcome, nor a conclusion that the groups had the same outcome. Absence of a reported result is not evidence of no effect.
Even if a group difference were reported, the interpretation would depend on the particular interaction pattern, the analysis population, missing-data handling, and statistical methods. A difference in a physiological conditioning measure would not automatically establish a difference in symptoms or later clinical outcomes. The record's stated purpose includes examining anxiety, depression, and stress-related symptoms, but numerical findings for those questions are not reported in the registry record.
The trial's randomized, double-masked, parallel-group design can support a comparative question in principle, but design labels alone do not resolve concerns about implementation, outcome availability, or analysis choices. The record does not provide enough information to assess those details. Its safety figures are descriptive counts and do not fill the gap in the primary efficacy result or determine whether reported events were caused by treatment.
The most defensible reading is therefore limited: the registry describes the intervention, comparator, design, and intended physiological endpoint, and it records certain adverse-event counts. It does not report the primary numerical outcome or enough analysis detail to quantify its uncertainty. Broader clinical conclusions are not established by this registry record.
13. Why This Trial Matters Statistically
This trial raises a useful statistical distinction between a group-average comparison and an interaction question. The primary endpoint is not simply whether mean skin conductance differs between active medication and placebo. It asks whether the relationship between CS type and trial pattern differs between groups. That distinction matters because a three-way interaction is interpreted through the combined pattern of responses, and an overall average alone may not capture it.
The outcome also illustrates the importance of measurement scale. The primary response is square-root transformed, so estimates and their uncertainty need to be interpreted with that scale in mind. Readers need the actual estimate, standard error or confidence interval, and a clear account of the analysis to judge both magnitude and precision. Those numerical results are not reported in the registry record.
The repeated trial structure raises general questions about dependence among measurements from the same participant and how uncertainty was estimated. The record does not report the statistical model or its handling of those relationships. This makes the endpoint description informative about the scientific question, but insufficient for evaluating the analysis itself.
The record also demonstrates why outcome registration and result reporting are distinct. It specifies the primary outcome and the timing of assessment, yet does not report the primary numerical finding, missing-data methods, analysis population, or multiplicity strategy. A completed trial status does not substitute for those results. The safety counts provide some descriptive information but cannot answer the primary interaction question.
Finally, planning assumptions are different from observed results. A planning illustration based on an observed effect cannot communicate the precision of the actual trial estimate, particularly when the observed effect and calculated planning values are not reported. Keeping these concepts separate helps prevent design assumptions from being mistaken for evidence about the endpoint.
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.
Several trial-specific limitations of interpretation follow from the information absent from the registry record. Most importantly, the numerical result for the primary outcome is not reported. There are no primary group summaries, interaction estimate, standard error, confidence interval, or p-value from which to assess direction or precision.
The population is not described beyond the fear-conditioning context. Eligibility criteria, participant characteristics, recruitment details, and the setting are not reported in the registry record. This limits assessment of which people the results might describe, even if the outcome result were available.
The registry identifies randomization, double masking, and a parallel model, but does not describe the randomization procedure, allocation concealment, who was masked, or whether masking was maintained. The actual allocation ratio is not reported. Treatment adherence, withdrawals, protocol deviations, and the number included in the primary analysis are also not reported in the registry record.
Statistical methods are insufficiently described for independent evaluation. The model, treatment of within-participant measurements across trial and stimulus type, covariate adjustment, analysis population, missing-data handling, and sensitivity analyses are not reported in the registry record. The reason for the square-root transformation and any interpretation on the original scale are also not reported.
The record lists two outcome measures but does not give full details or numerical results for the other measure. It does not state how multiplicity was addressed. Safety information is limited to event counts; event definitions, specific event terms, observation duration, and deaths are not reported in the registry record. Enrollment is recorded as 65, but the number contributing to outcome analyses cannot be determined from that count.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Influence of Escitalopram on Fear Conditioning — NCT01398514.
- Registry record last updated 2014-06-11; status last verified 2014-06.
- Results first posted 2013-09-27.
- 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.
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18. Record Summary
The registry record describes NCT01398514, “Influence of Escitalopram on Fear Conditioning,” as a completed randomized, double-masked, parallel-group phase 4 trial sponsored by Massachusetts General Hospital. Enrollment is recorded as 65. Escitalopram 10mg/day was compared with matched pill placebo. The trial start is recorded as 2008-10 and primary completion as 2011-06.
The primary outcome is mean square-root transformed skin conductance conditioned response during trials 1 to 4 of early extinction, assessed on Day 2 of the paradigm, 15 to 18 days post medication initiation. Its specified analysis question is a three-way interaction of group, CS type, and trial. The numerical primary result and its uncertainty are not reported in the registry record.
The registry lists two outcome measures and zero analysis entries. Safety counts record zero serious adverse events in each group and other adverse events affecting 13 in the active-medication group and 7 in the placebo group. Analysis methods, analysis populations, missing-data handling, multiplicity procedures, and further safety details are not reported in the registry record.