Ketamine in Borderline Personality Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ketamine in Borderline Personality Disorder (NCT03395314), a randomized phase 2 study. The primary outcome is Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS).

2. Clinical Question

3. Trial Design

The registry record describes a randomized, parallel-group, phase 2 trial with quadruple masking. Its official title identifies it as an active placebo controlled trial. The two interventions were low-dose ketamine and midazolam; the recorded arm descriptions specify intravenous administration over 40 minutes. The record reports enrollment of 22 participants and a terminated status. It gives a start date of 2018-02-15 and a primary completion date of 2022-05-06.

Random allocation is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured baseline characteristics. A parallel-group design assigns participants to one treatment group rather than crossing each participant between treatments. Masking is intended to limit the influence of treatment knowledge on participants, study staff, or outcome assessment. The registry identifies quadruple masking but does not specify which roles were masked or how masking was maintained.

Midazolam served as an active placebo comparator. This means the study compared ketamine with another administered drug, not with an untreated group. The comparator and infusion procedures are relevant to interpreting the treatment contrast, but the registry does not describe the comparator-selection rationale, procedural details beyond dose and duration, or any assessment of whether the masking was successful.

The primary outcome was change in suicidal thoughts measured using item 10 on the Montgomery-Asberg Depression Rating Scale. Assessments were planned at baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion. The record also lists secondary outcomes covering depression, anxiety, borderline personality symptoms, pain, social cognition, and social adjustment. It reports 21 outcome measures, but does not give results for those measures in the record.

Termination and enrollment are features of the study record, not explanations for why the trial ended or evidence about its treatment effects. The reason for termination and any implications for recruitment or follow-up 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intention to treat.

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 Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS), measured over Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion..

The primary endpoint concerns change in suicidal thoughts, measured with item 10 of the Montgomery-Asberg Depression Rating Scale (MADRS). The registry describes the MADRS as including 10 items, each using a 0 to 6 severity scale, with higher scores indicating increasing depressive symptoms. For item 10, the description identifies a range from 0, indicating enjoying life, to 6, indicating explicit plans for suicide. The primary outcome is expressed in units on a scale, with a least-squares mean and standard error as the stated summary measure.

Suicidal thoughts are the target of the primary endpoint because the study’s stated purpose was to test whether ketamine could decrease suicidality in borderline personality disorder. A repeated assessment schedule can describe the course of scores after infusion rather than restricting measurement to a single follow-up time. The registry lists baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion as planned timepoints.

The record does not report a single primary comparison, estimates at any timepoint, or a definition of how change across the multiple timepoints would be combined or tested. It notes that the outcome description was updated when results were entered, but the primary outcome values themselves are not reported in the registry record. Thus, the endpoint definition explains what was intended to be measured, not what the observed change was.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It identifies the trial as randomized and parallel-group, names the primary endpoint and planned timepoints, and specifies least-squares mean and standard error as the outcome summary. It does not describe the full analysis plan, provide primary-outcome estimates, or list analysis results. The following concepts explain how such methods are generally interpreted; they are not claims about analyses used in this trial unless explicitly stated in the record.

What does randomization contribute?

In general, random assignment helps create groups that are comparable at the start of a study, reducing the risk that treatment allocation is systematically related to participants’ characteristics. It does not guarantee that the groups will be identical, particularly in a small trial. The record calls this trial randomized but does not report the sequence-generation method, allocation concealment procedures, or baseline characteristics needed to assess the realized balance between groups.

The parallel design means each participant is assigned to one group. The recorded arms are low-dose ketamine and midazolam. The registry describes quadruple masking, but does not identify which participants or study personnel were masked. Masking may limit the influence of treatment knowledge on reported symptoms, care, and outcome assessment. Its success can depend on whether participants or staff can infer treatment assignment; whether that was evaluated is not reported in the registry record.

How should a least-squares mean be read?

In general, a least-squares mean is a mean estimated from a statistical model. Depending on the model, it can adjust for specified characteristics or account for other structure in the data. The registry record does not describe the model, covariates, or estimation procedure, so it is not possible to determine what adjustment the reported summary would represent. No least-squares mean values are reported for the primary endpoint.

A standard error expresses the estimated uncertainty of a mean or other estimate under the model’s assumptions. It differs from a standard deviation, which describes variation among participant measurements. A confidence interval, when reported, combines an estimate with an uncertainty range to show values reasonably compatible with the data and analysis assumptions. The registry record gives no primary-outcome standard errors or confidence intervals, so the precision of the treatment comparison cannot be assessed.

Why do repeated measurements need an analysis strategy?

The primary outcome was scheduled at baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion. Repeated scores from one participant are generally related rather than independent. General methods for repeated measurements account for that within-participant relationship and can use information across visits. The choice of model may affect the estimated group differences and their uncertainty. The registry record does not report whether the analysis used a repeated-measures model, separate comparisons at each timepoint, or another approach.

When an endpoint has several timepoints, there can be multiple possible treatment contrasts. A statistical plan may identify one primary timepoint, test an overall treatment-by-time pattern, or define another single primary question. The registry’s skip note indicates that the multiple timepoints were not reduced to one comparison. It does not report a test statistic, p-value, or estimate for any timepoint. Without a specified primary contrast, readers cannot infer which comparison was intended to carry the main confirmatory interpretation.

What does intention to treat mean in general?

Intention-to-treat analysis generally compares participants according to their randomized group, regardless of treatment adherence or discontinuation. This preserves the original randomized comparison and estimates the effect of assignment under the analysis strategy. The primary outcome population is identified as intention to treat in the registry. The record does not explain how missing measurements, withdrawals, or participants without follow-up data were handled, nor does it say how many participants contributed to each timepoint.

What can the planning illustration tell readers?

The registry’s sample-size assumptions describe a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustration considers the effect to detect as a stated fraction of the observed effect. It is not the trial’s original design justification and must not be read as observed power. The record does not report the trial’s own sample-size justification or provide the effect values needed to interpret numerical planning scenarios. Planning calculations describe hypothetical sample sizes under their assumptions; they do not replace the observed treatment estimate or its uncertainty.

In general, power is a design property tied to a specified effect, variability, analysis, and error rate. Calculating power using an observed effect after a study is complete does not establish the probability that the observed result is true. For this trial, the registry record does not report the primary effect or the trial’s original sample-size rationale. The planning illustration should therefore remain separate from any conclusion about the clinical outcome.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is planned for multiple assessments: baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion. Testing treatment differences at several times can raise a multiplicity concern: the more comparisons examined, the greater the chance of at least one apparently notable result by chance alone. General approaches include prespecifying one primary contrast, using an overall test, or adjusting inference across multiple comparisons. Which approach, if any, was planned or used is not reported in the registry record. The record indicates that this multi-timepoint outcome was not reduced to a single comparison.

The record lists 21 outcome measures, including the primary suicidal-thought measure and secondary measures of depression, anxiety, borderline personality symptoms, pain, social cognition, and social adjustment. Considering many outcomes can create additional multiplicity. The registry does not report a hierarchy among outcomes, a multiplicity adjustment, or which analyses were considered confirmatory versus exploratory. It reports zero analysis entries, so no analysis-specific results are available for assessing these issues.

The primary outcome population is identified as intention to treat. However, the handling of missing scores is not reported in the registry record. It does not state how missing measurements were addressed, whether participants who withdrew were followed for outcomes, or how many had data at each assessment. Missingness can affect estimates when the likelihood of an unavailable measurement is related to participants’ outcomes or treatment experience. Without the analysis method and missing-data information, the consequences for the treatment comparison cannot be assessed.

The registry also does not report interim analyses, stopping rules, or the statistical plan. Their absence from the record should not be taken to mean that none occurred. It means that readers cannot evaluate these design and analysis details from the registry information available.

11. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The safety record lists serious adverse events separately from other adverse events. In the midazolam group, 12 participants were at risk for serious adverse events and 0 were reported as affected; 12 were at risk for other adverse events and 7 were reported as affected. In the low-dose ketamine group, 10 participants were at risk for serious adverse events and 0 were reported as affected; 10 were at risk for other adverse events and 6 were reported as affected. The record lists no deaths in either group.

These figures count participants recorded as affected, not the total number of individual events. A participant may experience more than one event, and the record does not provide event descriptions or timing. The serious-adverse-event counts do not establish that serious harms are impossible; they describe what was recorded among the participants at risk in this trial. The other-adverse-event counts likewise do not indicate severity or whether events were considered related to treatment.

The groups are small, and the record does not provide uncertainty intervals or a formal safety comparison. The counts should therefore be read descriptively, not as proof that the groups have equivalent or different safety profiles. The registry does not report further detail about adverse-event collection or classification.

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

The study addressed a specific question: whether ketamine, compared with midazolam, was associated with change in suicidal thoughts measured with item 10 of the MADRS in borderline personality disorder. The registry record provides the randomized parallel-group design, planned outcome schedule, intervention descriptions, and some adverse-event counts. It does not provide primary-outcome estimates or analysis results. Consequently, it does not establish the direction, magnitude, or precision of any difference in suicidal thoughts between groups.

Not reporting a primary result is different from reporting a result that shows no difference. Without group estimates and an appropriate uncertainty measure, readers cannot determine whether the observed data were compatible with a range of effects or whether the study’s results were inconclusive. The registry also does not report the reason the trial was terminated or the completeness of outcome follow-up, so those aspects cannot be incorporated into an interpretation.

The safety counts are also limited. There were no serious adverse events reported in either group, while other adverse events were reported for 7 participants receiving midazolam and 6 receiving low-dose ketamine. These counts alone do not quantify a comparative risk or establish whether any event was caused by treatment. The registry does not include event descriptions, uncertainty estimates, or a formal safety analysis.

The design features describe how the comparison was intended to be conducted; they are not themselves evidence of a treatment effect. Randomization and masking can strengthen a comparison when implemented as planned, but the record lacks the outcome estimates and analysis details needed to judge the result. The sample-size planning illustration is a hypothetical calculation and is not observed power or evidence that the study could reliably detect a particular effect.

The appropriate interpretation is therefore bounded: the registry documents a trial designed to study this question, but its posted results do not permit a quantitative answer. It would be inappropriate to infer either benefit or lack of benefit from the absence of primary-outcome results.

13. Why This Trial Matters Statistically

This trial is statistically important because its primary question concerns a specific symptom outcome at multiple follow-up times, rather than a single measurement taken once. Repeated observations can describe how an outcome changes over time, but they also require an analysis strategy that accounts for the relationship among measurements from the same participant. The registry identifies the timepoints but does not report how they were combined or compared.

The study also illustrates the distinction between a trial’s design and its evidence. Randomization, a parallel-group structure, quadruple masking, and an active placebo describe features intended to support a fair comparison. Those features do not substitute for reporting estimates, uncertainty, missing-data handling, and the statistical analysis. In this record, the primary endpoint has no reported numerical results, and there are zero analysis entries.

The many listed outcomes make transparent analysis planning especially relevant. The registry reports 21 outcome measures and a set of secondary outcomes spanning several domains. When studies consider multiple outcomes and timepoints, readers need to know which questions were primary, how comparisons were prioritized, and whether multiplicity was addressed. Those details are not reported in the registry record.

Finally, the record separates descriptive safety counts from comparative inference. The small group counts and absence of serious adverse events in the record are useful to report, but without event detail or uncertainty they cannot resolve differences between treatment groups. The central statistical lesson is that design information and raw counts are not enough to establish an effect: the estimate, its precision, and the analysis context are essential.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpretation is that the registry record does not report primary-outcome results. It provides no estimates of suicidal-thought change, standard errors, confidence intervals, test statistics, or p-values. Therefore, the size and precision of the intended ketamine-versus-midazolam comparison cannot be assessed. The record also reports zero analysis entries, leaving no listed statistical analysis results to interpret.

The primary outcome was planned at multiple timepoints, but the record does not define a single comparison or explain how repeated measurements were analyzed. It does not report the statistical model, any covariate adjustment, or how within-participant correlation was handled. Although intention to treat is named as the primary population, the record does not describe handling of missing observations, withdrawals, or incomplete follow-up.

The record lists 21 outcome measures, but does not report a prespecified hierarchy, multiplicity strategy, or distinction between confirmatory and exploratory analyses. It also does not report an original sample-size justification, interim analyses, or detailed statistical plan. These omissions prevent assessment of how the analysis was planned and whether the reported outcomes, if any, followed that plan.

Enrollment was 22 and the study status is terminated, but the reason for termination is not reported in the registry record. The record does not state how many participants completed each assessment or whether all enrolled participants contributed primary-outcome data. The adverse-event information is limited to participant counts, without event descriptions, timing, or uncertainty estimates. The trial’s design and these counts can be described, but the unavailable results and methods limit conclusions about efficacy and comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Ketamine in Borderline Personality Disorder — NCT03395314.
• Registry record last updated 2023-06-26; status last verified 2023-05.
• Results first posted 2023-06-26.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a phase 2, randomized, quadruple-masked, parallel-group trial of ketamine versus midazolam for borderline personality disorder. It reports enrollment of 22 and a terminated status. The primary endpoint was change in suicidal thoughts measured using item 10 of the MADRS, with assessments planned from baseline through 28 days after infusion.

The record identifies intention to treat as the primary outcome population and least-squares mean with standard error as the outcome summary. It does not report primary-outcome estimates, analysis results, missing-data methods, or a single comparison across the planned timepoints. There were no serious adverse events reported in either group; other adverse events were reported for 7 midazolam participants and 6 low-dose ketamine participants. The reason for termination is not reported in the registry record.