NMDA Antagonists in Bipolar Depression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for NMDA Antagonists in Bipolar Depression (NCT01833897), a na phase 4 study. The primary outcome is Hamilton Depression Rating Scale (HAM-D).

2. Clinical Question

The registry describes a study intended to assess whether ketamine and D-cycloserine could be used safely and effectively for depression in people with bipolar depression. Its stated hypothesis was that ketamine would act rapidly and that D-cycloserine would serve as therapy following ketamine treatment. These are the investigators’ aims, not findings. The record lists eight participants enrolled and does not provide the primary HAM-D mean or standard deviation at the stated assessment time. It therefore does not allow a reader to determine the observed change in depression ratings or how precisely any treatment response was estimated.

3. Trial Design

This was a phase 4, single-group study with enrollment of 8. The registry lists allocation as NA and masking as NONE. The record’s own design classification and note indicate that this was not a randomized comparison and that the treatment group should not be read as a like-for-like control comparison. Consequently, it does not provide a randomized between-group estimate of treatment effect.

The treatment description starts with standard-of-care medication: quetiapine, olanzapine-fluoxetine, or lurasidone. Participants who remained symptomatic after about 2 week were to receive an infusion of ketamine hydrochloride at 0.5 mg/kg. The arm description says that participants who showed improvement after the ketamine phase would begin D-cycloserine, but the description is cut off before giving further details. The precise D-cycloserine schedule and other treatment procedures are not reported in the registry record.

The study start is recorded as 2013-03 and primary completion as 2014-07; its status is COMPLETED. Those dates describe the registry timeline and do not substitute for outcome reporting. The registry names New York State Psychiatric Institute as sponsor. It lists the primary outcome as final HAM-D score at 8 weeks, expressed as a mean with standard deviation. The record does not describe the analysis model, the timing of all measurements, or the details of the analysis population. Without a separate randomized comparator, observed outcomes would be descriptive of the participants and treatment sequence rather than a controlled estimate of the effect relative to another treatment.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: bipolar depression

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 Hamilton Depression Rating Scale (HAM-D), measured over 8 weeks.

The primary endpoint is the Hamilton Depression Rating Scale (HAM-D), recorded as a final score at 8 weeks. It is a continuous measure of depression severity: the registry describes a range from 0-53, with higher scores indicating worse depression. It also gives descriptive bands: 0-7 is normal, 8-13 is mild depression, 14-18 is moderate depression, 19-22 is severe depression, and ≥ 23 is very severe depression.

A continuous scale retains information across its range rather than reducing each participant to a simple category. Reporting a group mean describes the average score, while the standard deviation describes how spread out participants’ scores are around that mean. Those quantities would help characterize the observed endpoint, although the mean and standard deviation themselves are not reported in the registry record.

HAM-D is used in this study as a measure of depressive symptom severity, matching the population and the study’s stated interest in depression treatment. A score at one assessment time describes symptom level at that time; interpreting change would also require an appropriate baseline value and details of how repeated measurements were analyzed. Those baseline and analysis details are not reported in the registry record. The endpoint specification alone does not establish that a treatment caused a change, particularly in a single-group study without a randomized control comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the primary measure as continuous and specifies a mean and standard deviation for the final HAM-D score at 8 weeks. These are descriptive statistics. The mean represents the arithmetic center of observed scores; the standard deviation describes their variability around that center. In a clinical report, these summaries can help readers understand both the typical score and how similar or different participants’ scores were. Neither statistic is posted for the primary endpoint in this registry record.

A confidence interval is a general statistical tool for expressing uncertainty around an estimate. It gives a range of values compatible with the data and the method’s assumptions; a wider interval indicates less precision than a narrower one. No confidence interval for the primary outcome is reported in the registry record. Without an estimate and its uncertainty, readers cannot judge the range of plausible outcome values from the registry entry.

A p-value is a measure, under a specified statistical model and null hypothesis, of how surprising data at least as extreme as those observed would be. It is not the probability that a treatment works, nor does it describe the size or clinical importance of an effect. The record does not report a primary endpoint p-value or identify a statistical test. Accordingly, there is no posted inferential result to interpret. A p-value alone, even if available, would not resolve the design limitation created by the absence of a randomized comparison.

For a continuous outcome, a treatment comparison often uses a difference in group means or a model-based estimate adjusted for prespecified factors. Such an estimate would need a defined comparator and an appropriate analysis plan. Here, the registry identifies a single group and says the study is not a randomized comparison. It therefore does not support interpreting an unadjusted change over time as a randomized treatment contrast. The statistical model and any adjustment strategy are not reported in the registry record.

Repeated measurements can be analyzed in several ways. A report might compare baseline with follow-up, model scores at multiple times, or focus on a final assessment. These approaches answer related but distinct questions and can depend on assumptions about the data. The registry gives an endpoint timeframe of 8 weeks and describes a final score, but it does not provide a baseline value, measurement schedule, or repeated-measures analysis method. No particular analysis should be inferred from the endpoint label.

Over-dispersion is a general issue for count outcomes when observed variation exceeds what a simple count model expects. A model that ignores such extra variation can understate uncertainty. It is not possible to assess over-dispersion from the adverse-event summary alone, and the registry record does not describe a model for adverse events. The primary HAM-D measure is continuous, so this count-data issue does not define its analysis.

The record includes a sample-size planning illustration based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that such illustrations are planning calculations, not the study’s own design. The posted material does not include numerical illustration values in the registry record for interpretation, and the registry record does not report a trial-specific sample-size justification. In particular, a planning calculation must not be presented as observed power or as evidence that the enrolled sample was adequate. The actual study enrolled 8 participants in a single group, not two randomized arms.

For planning purposes, power describes the chance that a specified study design would detect a defined effect under its assumptions. It depends on the effect size, variability, analysis, and sample allocation. A calculation based on a selected fraction of an observed effect is an illustrative scenario, not a retrospective measure of what the completed study could detect. The registry’s statement about the illustration does not supply a protocol justification or establish that the design followed those assumptions.

Interpretation of any statistical result also depends on the analysis population: for example, whether results include everyone enrolled or only those with particular follow-up data. The registry record does not specify the population used for the primary analysis. It also does not describe how missing measurements were handled. These omissions matter because exclusions and missing-data methods can affect estimates, especially when a small group is involved. No approach should be attributed to the investigators without a reported description.

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("Ketamine and DCS Treatment")
n   <- c(8)
m   <- c(9.5)
sp  <- c(7)
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  Ketamine and DCS Treatment  8  9.500  7.000  3.648  15.352

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the HAM-D as the primary outcome and names secondary measures involving loss of motivated behavior on a HAM-D factor, the HAM-D suicide item, the Hamilton Anxiety Scale, and Beck’s Depression Inventory. It reports five outcome measures and five analyses. The entry does not explain which analysis corresponds to each measure, whether there were additional time points or contrasts, or whether a testing hierarchy was prespecified.

When several outcomes or statistical tests are examined, the chance of at least one apparently notable result can increase. This is a general multiplicity concern. Common approaches include identifying one primary test in advance, adjusting significance thresholds, or treating secondary analyses as exploratory. The registry record does not report whether any multiplicity adjustment or other strategy was used. Since numerical results are also absent, it is not possible to assess how multiplicity would affect interpretation of findings.

Missing-data handling is not reported in the registry record. The record does not state how many participants contributed an 8-week HAM-D score, whether any participants discontinued, or what method was used if outcome measurements were unavailable. It also does not specify an analysis population, such as all enrolled participants or a defined subset. These details are needed to understand which observations contributed to an estimate and whether the analysis could be affected by missingness.

The registry lists enrollment of 8, but that number alone does not establish the number analyzed for each outcome. The number with available observations at each assessment and the treatment of missing data are not reported. No assumptions about attrition, imputation, or exclusions can be made from the registry record.

12. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports 0 serious adverse events among 8 participants at risk in the Ketamine and DCS Treatment group. It also reports 4 events in the other adverse-event count among 8 participants at risk. These are the posted counts; the record does not provide the terms for the serious events, and the deaths field has no reported value.

The distinction between the serious-event count and the other-event count should be preserved. The registry does not provide enough detail to characterize the types, timing, duration, severity, or attribution of the other events. It also does not report participant-level data or describe how event monitoring and classification were carried out. The counts therefore do not indicate whether an event was related to a particular treatment or phase of the sequence.

These figures are descriptive, not a comparative safety estimate. The study has a single group, and there is no randomized control group against which to compare event counts. With enrollment of 8, the counts also give limited information about uncommon events. Neither the absence of a reported serious event nor the presence of other reported events establishes a general safety conclusion. The registry record does not provide the detail or comparison needed for that judgment.

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

The record documents a completed phase 4, single-group study focused on treatment in bipolar depression. It identifies standard-of-care medication, ketamine, and D-cycloserine in the treatment sequence and specifies HAM-D final score at 8 weeks as the primary endpoint. It also gives limited adverse-event counts. These details show what the study was intended to examine and what the registry entry reports about enrollment and safety.

The record does not report the numerical primary endpoint result, its variability, a confidence interval, or an inferential test. It therefore does not show the observed HAM-D score at 8 weeks or the precision of an estimate. The study’s hypothesis about rapid antidepressant action and follow-on D-cycloserine is not itself evidence that either treatment achieved those aims. No conclusion about treatment effectiveness can be drawn from an unreported outcome.

Even if outcome values were available, this single-group design would not provide a randomized contrast with another treatment or with no treatment. Scores observed during a treatment sequence cannot, by themselves, distinguish treatment-related changes from other influences. The sequence also means that the participants who received later treatment were selected according to their status after earlier treatment, as described in the registry. Separate effects of standard care, ketamine, and D-cycloserine cannot be identified from the information in this entry.

The safety counts should likewise be read narrowly. They describe reported event numbers for the enrolled group, not comparative risks or proof of safety. Event descriptions and a reported death count are unavailable in the registry record. The appropriate interpretation is therefore limited to the study design, endpoint specification, enrollment, and posted counts; claims about benefit, lack of benefit, or overall safety go beyond the reported data.

14. Why This Trial Matters Statistically

This record illustrates why a clearly named endpoint is not the same as a reported result. It identifies a clinically relevant continuous depression measure, its scoring direction, and the assessment timeframe. Yet without the observed mean, standard deviation, and analysis output, readers cannot assess the endpoint’s magnitude or precision. Transparent outcome reporting is needed for statistical interpretation, not only a protocol description.

The study also highlights the distinction between describing outcomes in a treated group and estimating a comparative effect. A single-group design can document what was observed among participants, but without a randomized comparison it cannot isolate treatment effects from other explanations for change. That distinction is particularly important when the intervention involves a sequence of treatments and later treatment is intended for a subset defined by response earlier in the sequence.

The record’s small enrollment makes clear why uncertainty and complete reporting matter. A group mean without a measure of variability would not show how dispersed participants’ outcomes were, and neither can be evaluated when the numerical outcome is absent. The posted adverse-event counts also demonstrate the limits of interpreting event totals without descriptions, follow-up details, or a comparison group.

Finally, the record names multiple outcomes but does not explain the analysis plan for them. Clear reporting of outcome hierarchy, analysis populations, and missing-data methods helps readers distinguish confirmatory analyses from exploratory ones and understand who contributed to each result. Those details are not reported in the registry record. The study is thus statistically informative as an example of how design and reporting determine which conclusions can be supported, even when its outcome results are unavailable.

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 central limitation for interpretation is that the registry record does not report the numerical result for the primary HAM-D endpoint. It also does not report its standard deviation, uncertainty interval, or statistical test. The size and precision of the observed endpoint therefore cannot be assessed.

The single-group design and lack of a like-for-like control comparison limit causal interpretation. Outcomes in this treatment sequence cannot be used as a randomized comparison of ketamine or D-cycloserine against another treatment. The record does not report separate estimates for the different components of the sequence.

The arm description is incomplete after stating that participants who improved after ketamine would begin D-cycloserine. The rest of the regimen is not reported in the registry record. Other details, including the full measurement schedule and the statistical analysis plan, are also not reported. The registry does not describe the primary analysis population, missing-data handling, or whether multiplicity was addressed across outcomes.

Although enrollment is recorded as 8, the number contributing data to each outcome is not reported. The registry lists five outcome measures and five analyses but does not provide the corresponding numerical results or explain their mapping. The safety entry gives event counts without event terms; the deaths field has no reported value. These gaps prevent fuller assessment of outcome completeness, safety patterns, and the statistical conclusions of the study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: NMDA Antagonists in Bipolar Depression — NCT01833897.
• Registry record last updated 2016-06-01; status last verified 2016-03.
• Results first posted 2016-06-01.
• 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

NCT01833897 is a completed phase 4, single-group study sponsored by New York State Psychiatric Institute, with enrollment of 8. Its recorded study start is 2013-03 and primary completion is 2014-07. The population is described as people with bipolar depression.

The treatment sequence began with standard-of-care options listed as quetiapine, olanzapine-fluoxetine, or lurasidone. Participants who remained symptomatic after about 2 week were to receive ketamine hydrochloride at 0.5 mg/kg. D-cycloserine was intended for participants who showed improvement after ketamine, but the registry description is incomplete.

The primary outcome is final HAM-D score at 8 weeks, summarized as a mean and standard deviation. Numerical primary and secondary outcome results are not reported in the registry record. The safety entry reports 0 serious adverse events among 8 at risk and 4 in the other adverse-event count among 8 at risk; serious-event terms are not listed, and the deaths field has no reported value.