Ketamine as a Rapidly-Acting Antidepressant in Depressed Emergency Department Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ketamine as a Rapidly-Acting Antidepressant in Depressed Emergency Department Patients (NCT02106325), a randomized phase 2 study. The primary outcome is Evaluate the Effects of Ketamine on Depressive Symptomatology by Measuring Change in Score on the Montgomery-Asberg Depressive Rating Scale.

2. Clinical Question

The trial was randomized and parallel, with triple masking recorded. The registry reports enrollment of 21 participants. Its brief summary says investigators planned to supplement self-reported mood measures with biological measures of major depressive disorder, but the specific biological measures and their results are not reported in the registry record.

3. Trial Design

This was a randomized, parallel-group Phase 2 trial sponsored by NYU Langone Health. The registry lists the study as completed, with a start date of 2013-12 and primary completion in 2016-02. Enrollment was 21. These administrative details describe the registered study; they do not establish how closely recruitment or conduct followed every element of the original plan.

Participants were assigned to ketamine or diphenhydramine. The ketamine arm description gives an intravenous dose of 0.25mg/kg, and the diphenhydramine arm description gives 25mg. The record identifies the study as triple-masked, but it does not identify the masked groups of people or describe how masking was maintained. The design is listed as parallel rather than crossover, so the registered comparison is between separate randomized arms.

The study focused on people with depression presenting to an emergency department. The brief summary refers to major depressive disorder and severe depression, but detailed eligibility criteria, recruitment procedures, sites, and exclusion criteria are not reported in the registry record. Nor is the intended sample-size justification reported in the registry record. Enrollment is an observed registry figure, not a statement about the target sample or the reasoning behind it.

The primary outcome is described as change in Montgomery-Åsberg Depression Rating Scale score. The listed timeframe says baseline and 16 weeks, whereas the measurement description says 40 minutes post infusion. These descriptions do not align clearly, and the record does not explain whether they refer to different assessments or which timing defines the primary analysis. The reported outcome values are group means with standard errors, but the registry does not provide a sponsor-reported analysis or explain how the endpoint was constructed from repeated measurements.

The registry lists secondary outcomes concerning treatment alliance, suicidal ideation, inpatient stay, outpatient follow-up compliance, and inpatient treatment alliance. Detailed numerical results are posted for only some of these outcomes. The record does not report a statistical analysis plan, an interim-analysis plan, or details of the analysis population.

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.

Phase 1

Reasons for not completing this period:

Phase 2

Reasons for not completing this period:

Phase 3

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.

6. Primary Endpoint

The registry lists the primary outcome as Evaluate the Effects of Ketamine on Depressive Symptomatology by Measuring Change in Score on the Montgomery-Asberg Depressive Rating Scale, measured over Baseline and 16 weeks.

The primary endpoint is described as change in score on the Montgomery-Åsberg Depression Rating Scale, a measure of depressive symptomatology. The registry description says the instrument has nine questions and an overall score ranging from 0 to 54 points. It also gives score bands for normal or absent symptoms, mild depression, moderate depression, and severe depression, with the last category described as above 34. Such a scale provides a structured way to quantify symptoms rather than relying only on an unstructured impression.

The registry identifies the outcome unit as units on a scale and says the summary measure is a mean with standard error. The posted arm summaries are means of 28.82 for ketamine and 25.2 for diphenhydramine. The comparison is a mean difference of -3.62, with a 95% confidence interval from -12.01 to 4.767 and an unadjusted p-value of 0.398. These are the posted numerical summaries; the record does not include a sponsor-reported analysis explaining the construction or interpretation of the change score.

There is an important timing ambiguity. The primary outcome timeframe is recorded as baseline and 16 weeks, while the description says 40 minutes post infusion. Since timing can affect what a score represents and which observations are compared, the registry record does not make the primary endpoint’s intended assessment time fully clear. The measure is relevant to the stated question about depressive symptoms, but the posted information does not resolve that ambiguity.

7. Results Posted in the Registry

• Diphenhydramine: mean 25.20 versus 28.82 on control; difference -3.62 (95% CI -12.01 to 4.77), standardized effect d = -0.37; z-test p = 0.398.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change in Treatment Alliance Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Diphenhydramine: mean 53.15 versus 43.52 on control; difference 9.63 (95% CI -1.28 to 20.54), standardized effect d = 0.76; z-test p = 0.084.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Diphenhydramine and the control. The interval gives the range of effects that remain compatible with the data.

Beck Scale for Suicidal Ideation (BSSI)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Diphenhydramine: mean 1.08 versus 1.58 on control; difference -0.50 (95% CI -4.41 to 3.41), standardized effect d = -0.11; z-test p = 0.802.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Diphenhydramine and the control. The interval gives the range of effects that remain compatible with the data.

Montgomery-Åsberg Depression Rating Scale Suicide Ideation Item (MADRS-SI)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Diphenhydramine: mean 0.75 versus 0.83 on control; difference -0.08 (95% CI -1.27 to 1.11), standardized effect d = -0.06; z-test p = 0.896.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Diphenhydramine and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcomes cover several different domains, including treatment alliance and suicidal ideation. Detailed numerical arm summaries and recalculated comparisons are available for treatment alliance, the Beck Scale for Suicidal Ideation, and the Montgomery-Åsberg Depression Rating Scale suicide-ideation item. The registry also lists inpatient stay, outpatient follow-up compliance, and inpatient treatment alliance, but numerical results for those outcomes are not reported in the registry record.

Across the secondary measures with numerical results, the estimates do not form a uniformly clear pattern. Their confidence intervals include zero, and the comparisons are unadjusted. This means the secondary summaries neither provide strong independent confirmation of the primary comparison nor resolve the primary result’s uncertainty. They measure related but distinct constructs, so agreement or disagreement would not be expected to map perfectly onto the primary depression score.

Secondary outcomes are often useful for understanding a trial’s breadth, possible mechanisms, and outcomes that matter beyond the primary measure. But when several outcomes are assessed, chance alone can produce apparently notable findings. Unless the testing plan and any multiplicity adjustment are known, isolated secondary estimates deserve less weight than a prespecified primary outcome. The registry does not report a hierarchy, adjustment method, or full analysis plan. Accordingly, the secondary results are best interpreted as exploratory descriptions rather than as confirmatory tests.

The record reports nine outcome measures and zero reported analyses. The fact that outcomes are listed does not mean that every measure has a posted result or that all possible analyses are documented. In particular, missing results for the listed length-of-stay and follow-up outcomes prevent an overall assessment across every registered secondary domain. The available secondary summaries should be considered alongside the primary estimate’s wide interval and the uncertainty over endpoint timing, not as replacements for them.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change in Treatment Alliance Score
• Beck Scale for Suicidal Ideation (BSSI)
• Montgomery-Åsberg Depression Rating Scale Suicide Ideation Item (MADRS-SI)
• Length of Inpatient Stay
• Outpatient Follow-up Compliance
• Inpatient Treatment Alliance Scale (ITAS)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is measured in units on a scale, and the registry reports means and standard errors. For a continuous outcome, a mean describes the group’s average score, while a standard error describes uncertainty in the estimated mean. A standard error is not the same thing as the spread of individual participant scores. It is useful for estimating precision of a group mean, but it does not show the full range of outcomes among participants.

What does the mean difference represent?

The primary comparison is a mean difference. The posted comparison labels diphenhydramine as the comparison arm and gives a mean difference of -3.62. The accompanying arm means are 28.82 for ketamine and 25.2 for diphenhydramine. In this contrast, the negative sign reflects the direction of the difference as defined in the posted comparison; it is not by itself a judgment about clinical importance. The registry does not report a threshold for a clinically meaningful change, so the practical importance of a particular score difference cannot be established from this record.

A mean difference retains the scale’s original units, which can make it easier to relate to the instrument. Its interpretation depends on what outcome was calculated and when it was measured. Here, the registry describes change in score but gives timing information that is inconsistent: baseline and 16 weeks in one field, and 40 minutes post infusion in the description. The record does not explain which observations were used in the posted comparison or how any repeated observations were combined.

What does a confidence interval add?

A confidence interval gives a range of estimates compatible with the observed data under the calculation’s assumptions. It conveys both direction and precision. An interval that includes zero does not rule out a difference; it indicates that the data and method do not sharply distinguish the estimate from zero. A wide interval signals that the estimate is imprecise. The primary interval, from -12.01 to 4.767, includes zero and spans values on both sides of it, so the direction and size of the underlying difference remain uncertain.

The associated unadjusted p-value is 0.398. A p-value measures the compatibility of the observed data with a null model, assuming the method’s assumptions hold. It is not the probability that the null hypothesis is true, and it does not measure the probability that the result will replicate. An unadjusted value also does not account for testing multiple outcomes unless such adjustment is explicitly included. No multiplicity adjustment is reported in the registry record.

Why is the standard error not the standard deviation?

The standard deviation describes variation among individual measurements. The standard error describes uncertainty in an estimated mean. The registry posts standard errors for the arm means, rather than standard deviations. Reconstructing a comparison from summary information requires assumptions about the relationship between the reported quantities and the analysis. The displayed recalculations use the posted summary statistics and are simple, unadjusted comparisons; they are not a substitute for an individual-participant-data analysis or an undocumented sponsor model.

General statistical principle: when observations are more variable than a simple model assumes, uncertainty can be understated if that extra variation is ignored. This is often described as over-dispersion. The registry does not report that over-dispersion was present or describe a model for it in this trial. Because no sponsor analysis is reported, it is not possible to assess whether a more complex model, covariate adjustment, or repeated-measures approach was used.

How should the secondary comparisons be treated?

Secondary comparisons use the same broad idea of comparing group means, but they address different outcomes and do not automatically carry the same evidential status as the primary endpoint. Multiple outcomes create more opportunities to observe an apparently notable result by chance. A prespecified testing hierarchy or adjustment can address this issue, but neither is reported in the registry record. The secondary estimates should therefore be read as unadjusted and exploratory, especially given the limited enrollment and the uncertainty in their intervals.

The registry lists nine outcome measures and records zero reported analyses. That distinction matters: outcome summaries and recalculated comparisons do not constitute a complete, prespecified analysis report. The record does not describe the treatment of missing measurements, the primary analysis population, covariates, sensitivity analyses, or whether the analysis followed an intention-to-treat principle. These details are necessary to judge the full statistical analysis.

What can be inferred from the displayed summaries?

The posted means and standard errors permit a descriptive comparison and an approximate interval-based assessment. They do not establish causation beyond what the randomized design could support under appropriate conduct and analysis. Randomization helps balance prognostic factors on average, but the registry does not report the allocation procedure, concealment, adherence, or masking checks. The small enrolled sample also leaves room for chance imbalance. General principle: randomization is a design safeguard, not a guarantee that every relevant characteristic is balanced in a particular trial.

The record’s timing ambiguity further limits the interpretation of a mean difference. A score at 40 minutes post infusion and a comparison involving baseline and 16 weeks would address different time points and potentially different clinical questions. The registry does not clarify which applies to the posted result. Thus the statistics can be interpreted as summaries of the recorded comparison, but the exact endpoint contrast and its intended clinical meaning remain incompletely specified.

11. Confidence Intervals and Precision

The primary mean difference is -3.62, with a 95% confidence interval from -12.01 to 4.767. The interval includes zero and covers estimates on both sides of zero. It therefore does not establish a clear direction for the difference. Its width also indicates that the point estimate is not precise: values notably different from the point estimate remain compatible with the posted summary and calculation.

A confidence interval is not a range containing 95% of individual participants’ scores. In general statistical terms, a 95% confidence interval describes the long-run performance of the interval-producing procedure under its assumptions. For a particular trial, it is a way to show estimation uncertainty, not a guarantee that the true effect lies in the displayed range. The interval’s interpretation also depends on the analysis and endpoint being correctly specified.

The posted group means have standard errors of 2.95 for ketamine and 3.1 for diphenhydramine. These indicate uncertainty around the estimated means, not the full variability of scores among participants. The registry does not report individual-level distributions, so those cannot be assessed from the posted summary. The comparison interval is the more direct statement of precision for the group contrast.

The reported interval and p-value are unadjusted recalculations from the posted summary statistics, not a sponsor-reported inferential analysis. The record does not report a prespecified interval method or analysis plan. In addition, the primary endpoint timing is described inconsistently as baseline and 16 weeks and as 40 minutes post infusion. Even a numerically precise interval would not resolve uncertainty about which time contrast the endpoint represents; the present interval is also broad enough that the estimated difference remains uncertain.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial’s original design justification. The trial’s own sample-size assumptions are not reported in the registry record. The planning calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They use an effect to detect equal to the stated fraction of the observed effect. For these continuous-outcome calculations, the figures refer to participants per arm, not total events.

The 80% power column gives the estimated participants per arm for a future study to have an 80% chance of detecting the specified effect under those assumptions, if that effect is truly present. The 90% power column gives the corresponding planning figure for a higher chance of detecting that effect. These are design targets, not guarantees. A study’s actual results can differ from the expected behavior used in planning.

The rows describe planning for 100%, 75%, and 50% of the observed effect. Smaller effects are harder to distinguish from random variation, so detecting them requires more participants under otherwise similar assumptions. For example, the primary comparison’s illustration gives 115 participants per arm for 80% power when planning for 100% of the observed effect, and 460 participants per arm when planning for 50% of it. These estimates depend on the observed effect, which can be unstable in a small trial, and should not be treated as a reliable forecast of a future study’s outcome.

This is not observed power. It is an illustration of sample sizes for future planning under specified assumptions, not a retrospective measure of the trial’s success or adequacy. The registry does not report whether these assumptions match the original protocol or whether other considerations shaped the trial’s target enrollment.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -3.620; pooled standard deviation σ = 9.793.
2. n = 2 × (1.96 + 0.842)² × 9.793² / -3.620² = 114.9, rounded up to 115 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -3.62                      # observed difference in means
sigma <- 9.7930560791012                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2106325)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 115 (80% power), 154 (90% power)
 75% of observed effect: n per arm = 205 (80% power), 274 (90% power)
 50% of observed effect: n per arm = 460 (80% power), 616 (90% power)
power.t.test: 115.9 
Simulated power at n = 115 per arm: 0.791 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes, including a primary depression measure and secondary measures of treatment alliance, suicidal ideation, inpatient stay, and follow-up compliance. Testing several outcomes raises a multiplicity issue: the more separate comparisons examined, the more likely it is that at least one will appear notable by chance, even if no underlying effect exists. General statistical practice can address this through prespecified outcome hierarchies, adjusted significance thresholds, or other planned procedures. The registry record does not report whether any such approach was specified or used.

The posted secondary comparisons are unadjusted. Their p-values should therefore not be interpreted as if the number of outcomes examined had no bearing on false-positive risk. The record also does not report which secondary analyses, if any, were prespecified or whether the reported measures were selected after examining the data. These omissions limit the strength of conclusions based on secondary results.

Missing-data handling is not reported in the registry record. There is no information about the amount or timing of missing outcome measurements, reasons for missingness, imputation, or sensitivity analyses. That matters because a complete-case comparison can be misleading if the people with observed outcomes differ systematically from those without them. No particular pattern of missingness can be inferred from the posted summaries.

The analysis population is also not reported in the registry record. The record does not say whether participants were analyzed according to randomized assignment, according to treatment received, or under another rule. It does not describe adherence, protocol deviations, or exclusions from analyses. These details are important for assessing how randomization was preserved in the analysis and how the reported comparison relates to the trial’s assigned groups.

Finally, the registry does not report a full statistical analysis plan or sponsor-reported analyses. The listed outcome summaries and recalculated comparisons provide useful descriptive information, but they do not answer questions about prespecification, covariate adjustment, repeated measurements, or robustness checks. These gaps should temper interpretation rather than be filled by assumptions about standard trial practice.

15. 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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: psychosis and suicidality (9.1%).

The registry reports serious adverse events affecting 1 participant in the ketamine arm and 0 in the diphenhydramine arm. The corresponding numbers at risk are 11 and 10. It reports other adverse events affecting 8 participants in each arm, with 11 and 10 at risk, respectively. No deaths are reported in either arm.

These counts describe events recorded during the trial; they do not by themselves establish whether an event was caused by the assigned intervention. The record does not provide event-level descriptions, timing, severity beyond the serious-event classification, or a sponsor assessment of causality for each event. It also does not provide enough detail to evaluate differences in duration of exposure or completeness of adverse-event collection.

The registry lists Psychosis and Suicidality as the top serious-event term, at 9.1%. It does not specify in this summary how that term is distributed by arm or give its denominator. It should therefore not be assigned to a particular group from the available information. With a small trial, event counts are descriptive and imprecise; zero reported deaths does not establish the absence of risk, and the observed counts cannot characterize uncommon harms reliably.

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

The result provides a small randomized comparison of ketamine and diphenhydramine among depressed emergency-department patients. The posted primary mean difference is -3.62, with a 95% confidence interval from -12.01 to 4.767 and an unadjusted p-value of 0.398. The interval includes zero and is broad, so the estimate does not establish a clear direction or a precise magnitude of difference.

This does not show that the two interventions are equivalent. Equivalence requires a prespecified margin and an analysis designed to assess whether the plausible difference is sufficiently small. Such a margin and analysis are not reported in the registry record. Nor does the result establish that ketamine does or does not produce a clinically meaningful change: the registry does not provide a threshold for meaningful change, and the endpoint timing is not clearly consistent across its descriptions.

The randomized design is relevant because random allocation can reduce confounding in a comparison, but the registry’s design label alone cannot confirm every aspect of conduct. Allocation concealment, adherence, masking checks, missing outcomes, and analysis populations are not reported in the registry record. The posted comparisons are recalculations from summary statistics rather than a fully documented sponsor analysis.

The secondary findings do not settle these uncertainties. They address other measures, are unadjusted, and are not all reported numerically. The safety counts are also limited descriptions, not a complete characterization of potential risks. Together, these data are best understood as a record of outcomes from a small completed trial, with substantial uncertainty and important reporting gaps. They do not justify broad conclusions about all patients or settings, and they do not replace a larger, fully reported analysis with a clearly defined endpoint and analysis plan.

17. Why This Trial Matters Statistically

This trial illustrates why effect estimates and their uncertainty should be read together. The primary comparison has a specific point estimate, but its confidence interval spans values on both sides of zero and covers a broad range. Focusing only on the point estimate or on whether a p-value crosses a conventional threshold would omit much of what the data say about precision.

It also illustrates how endpoint definition is part of statistical interpretation. A score described as a change from baseline and a score recorded 40 minutes after infusion do not necessarily answer the same question as a comparison described at baseline and 16 weeks. When the registry record gives conflicting timing descriptions, readers cannot confidently connect the numerical contrast to a single assessment schedule. Clear outcome definitions are essential for reproducible analysis and clinically meaningful interpretation.

The record also shows the distinction between a trial’s observed enrollment and planning for a future study. The planning illustrations use the observed effect and stated assumptions; they do not reveal the original design rationale and are not observed power. Smaller target effects imply larger planning requirements, but those calculations depend on assumptions and an effect estimate that may be unstable in a small trial.

Finally, multiplicity and reporting completeness matter. Several secondary outcomes are listed, yet the registry does not report a testing hierarchy or adjustment, and some listed outcomes have no numerical results. A transparent analysis plan, missing-data account, and clearly identified analysis population would help readers distinguish confirmatory evidence from exploratory patterns. These are general statistical lessons illustrated by the trial record, not claims about unreported trial procedures.

18. 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 trial enrolled 21 participants, limiting the precision of group estimates and the ability to characterize less common outcomes. The primary confidence interval is broad, and the record offers no evidence that the estimate is sufficiently precise for a narrow conclusion. The posted planning calculations do not remedy this limitation; they are illustrations based on the observed effect, not the original design justification.

The endpoint timing is unclear because the registry lists baseline and 16 weeks as the timeframe but describes measurement 40 minutes post infusion. The record does not reconcile these descriptions or explain which assessment generated the posted primary comparison. This makes the intended estimand and the clinical interpretation of the estimate uncertain.

The registry does not report detailed eligibility criteria, recruitment procedures, treatment adherence, allocation concealment, or masking checks. It also does not report missing-data methods, the analysis population, a full statistical analysis plan, or sponsor-reported inferential analyses. These omissions prevent assessment of whether the posted summaries reflect the planned analysis and how robust they are to alternative assumptions.

Several secondary outcomes are listed, but numerical results are not reported for all of them. No multiplicity procedure is reported, and unadjusted secondary results should be treated cautiously. Safety information is limited to group counts and a listed serious-event term; event-level details, causality assessments, and fuller exposure information are not reported in the registry record. These limitations are specific to the information documented for this trial and do not establish that the unreported procedures or analyses were not performed.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Ketamine as a Rapidly-Acting Antidepressant in Depressed Emergency Department Patients — NCT02106325.
• Registry record last updated 2018-09-14; status last verified 2018-08.
• Results first posted 2018-09-14.
• 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.

22. Record Summary

NCT02106325 is a completed, randomized, parallel-group Phase 2 trial sponsored by NYU Langone Health. The registry lists triple masking, enrollment of 21, a start date of 2013-12, and primary completion in 2016-02. It compared intravenous ketamine at 0.25mg/kg with 25mg diphenhydramine among depressed emergency-department patients.

The primary outcome is described as change in Montgomery-Åsberg Depression Rating Scale score. The posted means are 28.82 for ketamine and 25.2 for diphenhydramine; the mean difference is -3.62, with a 95% confidence interval from -12.01 to 4.767 and an unadjusted p-value of 0.398. The timing description is inconsistent, and the registry does not report a sponsor analysis or a complete statistical analysis plan.

Secondary outcomes cover treatment alliance and suicidal ideation, among other domains. Numerical results are available for some measures, while results for other listed outcomes are not reported in the registry record. The posted safety counts include 1 serious adverse event in the ketamine arm, none in the diphenhydramine arm, and no deaths in either arm. Overall, the record supports a descriptive account but leaves substantial uncertainty about precision, endpoint timing, and analysis details.