Depakote ER in Bipolar Depression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Depakote ER in Bipolar Depression (NCT00186186), a na phase 4 study. The primary outcome is Montgomery Asberg Depression Rating Scale (MADRS).

2. Clinical Question

In statistical terms, the record identifies a treatment question and an outcome schedule, but the information available does not provide a numerical estimate of outcome change. Without posted outcome values, it is not possible to quantify the study-group trajectory or its uncertainty. The single-group design also means that changes over time, if reported, would not by themselves separate an intervention-associated change from other explanations, such as the natural course of symptoms or influences not controlled by the study design.

3. Trial Design

The registry record describes Depakote ER in bipolar depression as a completed Phase 4 study sponsored by Stanford University. The study began in 2004-01, had primary completion in 2009-01, and is recorded as completed. Enrollment is listed as 28. These are record-level design details; the record does not provide additional information about recruitment, retention, or the number of participants contributing to each analysis.

The intervention is Depakote ER, described as up to 1500 mg/day. The model is recorded as single group, allocation as NA, and masking as none. No control arm is described. Accordingly, this design is not a randomized comparison, and any outcome data from the treated group would need to be interpreted as observations within that group rather than as a treatment effect relative to a concurrent control.

The primary outcome is MADRS, a continuous measure reported as a mean with standard deviation. Its timeframe is baseline and 7 weeks. The study purpose additionally names safety and efficacy, metabolic and GABA changes, and PET and MRI/MRS imaging. The listed secondary outcome is “Response to the Divalproex-ER in Acute Bipolar 2 Depression.” The registry record does not report the methods or results for the imaging measures in the information.

The record lists two outcome measures and two analyses. It does not explain how those analyses relate to the outcomes, which analysis populations were used, or whether repeated measurements were analyzed as paired observations. The statistical plan, including any adjustment strategy or treatment of missing measurements, is not reported in the registry record. These omissions limit what can be concluded about how the design was implemented and how any results should be interpreted.

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:

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 Montgomery Asberg Depression Rating Scale (MADRS), measured over Baseline, 7 weeks.

The primary endpoint is the Montgomery-Åsberg Depression Rating Scale (MADRS), described as a ten-item diagnostic questionnaire used by psychiatrists to measure the severity of depressive episodes in people with mood disorders. The registry states that higher scores indicate more severe depression and that the overall score ranges from 0 to 60. It also gives customary score bands: 0 to 6 as normal or symptom absent, 7 to 19 as mild depression, and 20 to 34 as moderate depression; scores >34 are described as severe.

Using a standardized scale gives researchers a defined way to describe symptom severity and to compare measurements over time within a study. The registry specifies measurements at baseline and 7 weeks, which identifies the intended observation points. However, the record does not report the mean or standard deviation at either time point, nor does it report a change estimate or uncertainty interval. The endpoint description therefore explains what was intended to be measured, but does not provide evidence about the observed symptom course.

The outcome is classified as continuous and its parameter as a mean. A mean describes the group’s average score, while a standard deviation describes variation among scores around that average. Neither quantity alone indicates how many participants improved, and a group average does not describe every participant’s experience. The listed secondary response outcome is separate from the primary continuous MADRS measure; its definition and results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies MADRS as a continuous outcome summarized by a mean and standard deviation. Those summaries answer different questions. The mean locates the average score in the group; the standard deviation describes how dispersed participant scores are around that average. A standard deviation is not the uncertainty of the mean. General statistical explanation: uncertainty about a mean depends both on the variability in observations and on how many observations contribute, so a mean and standard deviation do not, by themselves, give a confidence interval for the mean or for change.

What would a baseline-to-follow-up estimate describe?

Because the stated timeframe includes baseline and 7 weeks, an analysis could describe the group’s scores at each time point or estimate within-person change for participants measured at both times. These are not interchangeable summaries. Comparing two group means can involve different contributing participants if measurements are missing, while a paired change uses observations from people with measurements at both time points. The registry record does not say which approach was used, whether the analysis was paired, or how missing measurements were handled.

A confidence interval, as a general statistical concept, gives a range of estimates compatible with the data and the interval procedure. It communicates precision, not certainty that a particular value is true. A narrow interval indicates greater precision than a wide interval under the same procedure. No confidence interval for MADRS is reported in the registry record, so the precision of any change cannot be assessed from the posted information. A p-value, if reported, would address compatibility with a specified null model; it would not measure the size or clinical importance of an effect. No p-value for the primary outcome is reported.

Why does the single-group structure matter?

A single-group analysis can describe the observed course of outcomes among participants with available data. It cannot provide the same causal contrast as a randomized comparison with a control group. Even a statistically clear change from baseline would not, on its own, identify what would have happened over the same period without the intervention. The registry records no comparator and no random allocation, so an interpretation based on a between-group treatment effect is not supported by the stated design.

The outcome is measured on a bounded scale, with the registry describing a total range from 0 to 60. General statistical explanation: when interpreting a mean on a bounded scale, it is useful to consider the possible range and the distribution of individual scores, rather than treating the mean as a complete account of participants’ outcomes. The record provides no distributional summaries, individual-level data, or endpoint results. It is therefore not possible to assess score patterns, departures from modeling assumptions, or the presence of unusually influential observations.

What can planning calculations establish?

Sample-size calculations are planning illustrations, not observed results. The stated calculation assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The registry study itself is single group, so the two-arm planning setup does not match its recorded design. These calculations should not be read as the trial’s own design justification, as evidence that a target sample size was prospectively selected, or as observed power. The record does not report a sample-size justification or its underlying assumptions.

A planning calculation based on an observed effect also depends on the effect estimate used. Since the primary MADRS results are not reported in the registry record, no numerical interpretation of such an illustration can be grounded in the posted primary outcome results. Any planning values associated with fractions of an observed effect are hypothetical design scenarios, not additional participants observed in this study. They do not repair the absence of a control group or provide a causal estimate.

How should multiple outcomes be viewed?

The record lists two outcome measures and two analyses, but does not explain the relationship between them or report a multiplicity strategy. When several outcomes or analyses are examined, general statistical practice considers whether the number of opportunities to identify a result affects interpretation. The registry record does not say whether outcomes were prespecified in a hierarchy, whether any adjustment was planned, or which results were considered confirmatory. It is therefore not possible to infer how multiplicity was addressed.

In short, the statistical labels establish that the primary measure is continuous and that mean and standard deviation were the intended summary form. They do not reveal the fitted analysis, the estimate, its uncertainty, or the handling of unavailable data. Those details are not reported in the registry record, so interpretation must remain limited to the design and outcome definitions that are recorded.

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("Depakote ER")
n   <- c(20)
m   <- c(14.9)
sp  <- c(9.8)
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  Depakote ER  20  14.900  9.800  10.313  19.487

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and two analyses. It does not report a hierarchy among outcomes, identify which analyses correspond to which measures, or state whether the primary and secondary outcomes were handled as separate confirmatory questions. A multiplicity adjustment or other strategy for interpreting multiple analyses is not reported in the registry record. The number of listed measures and analyses alone does not show whether or how multiplicity was considered.

Missing-data procedures are also not described. The record does not report the number of participants with MADRS observations at baseline or 7 weeks, reasons for unavailable measurements, or whether any imputation or other missing-data method was used. Enrollment is listed as 28, but the number contributing to each outcome analysis is not reported in the registry record. Therefore, it cannot be assumed that all enrolled participants contributed measurements at both time points.

The analysis populations are not reported in the registry record. There is no stated definition of who was included in the primary analysis, such as whether inclusion depended on receiving the intervention or having measurements at particular time points. The registry describes Depakote ER up to 1500 mg/day but does not report individual exposure, adherence, or analysis by dose.

These gaps affect both interpretation and precision. Different analysis populations or approaches to missing observations can produce different estimates, particularly when the availability of measurements is related to participants’ outcomes. Without the analysis definitions and outcome data, the robustness of any result cannot be assessed. No specific missing-data or multiplicity method should be inferred from the completed status of the study or from the count of listed analyses.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry records zero serious adverse events among 28 participants at risk for serious events. It records 3 other adverse events among 28 participants at risk for other events. These are counts as entered in the registry; they are not risk differences or rates, and no comparative group is described. The serious adverse-event terms are not listed. The deaths field is null, so deaths are not reported in the registry record rather than established as absent.

The labels distinguish serious adverse events from other adverse events, but the information does not define the criteria used for each category or provide individual event descriptions. It also does not report timing, duration, severity details beyond the serious/non-serious grouping, whether an event led to stopping treatment, or the investigators’ assessment of relatedness to Depakote ER. The counts therefore do not show what events occurred or whether they were attributed to the intervention.

Without a comparator, the counts cannot establish whether the observed event experience differed from what would have occurred under another condition. The registry figures are a limited safety description, not a complete assessment of safety. The available information also does not establish whether all participants were followed for the same period or whether all adverse events were captured.

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

The record establishes that this was a completed, single-group study of Depakote ER in bipolar depression, with MADRS identified as the primary measure at baseline and 7 weeks. It also identifies the intended dose description and a secondary response outcome. Those details clarify the clinical questions the study set out to address. They do not supply an estimate of the primary outcome or its precision.

Because the registry record does not report MADRS results, it does not show whether average scores increased, decreased, or remained similar over the stated timeframe. It also does not provide a confidence interval or other measure of uncertainty. No conclusion about the size or clinical importance of a change can be drawn from the endpoint definition alone. The score bands describe how the scale is commonly interpreted; they are not outcome findings for this study.

Even if within-group outcome results were available, the single-group design would constrain causal interpretation. A change over time in one group would describe what was observed in that group, but would not isolate the intervention’s effect from other influences over time. There is no recorded control condition against which to make a randomized comparison.

The safety counts indicate that the registry recorded zero serious adverse events among 28 at risk and 3 other adverse events among 28 at risk. They do not provide event descriptions, comparative rates, or a complete account of safety monitoring. Deaths are not reported in the registry record.

Thus, what the record does show is the study structure, outcome definitions, timeframe, and limited adverse-event counts. What it does not show is the primary result, its statistical precision, results for the listed secondary outcome, or findings for the imaging aims. These limitations do not establish that the study found no effect; they mean the posted registry information is insufficient to characterize the clinical outcomes.

14. Why This Trial Matters Statistically

This study illustrates why a registry’s design information and its results information need to be read separately. The record gives a clear primary outcome label, the measure used, and the intended measurement timeframe. Those details help define what an analysis would need to estimate. Yet without the means, standard deviations, or a change estimate, the magnitude and precision of the primary outcome remain unknown.

Its single-group structure is also statistically important. A group’s change over time can be described, but the absence of a comparator limits the ability to distinguish intervention-associated change from other possible explanations. This distinction is central to the interpretation of evidence: a within-group observation is not equivalent to a randomized treatment-versus-control contrast.

The record also demonstrates the value of clear reporting about analysis populations, missing measurements, and multiplicity. It lists two outcomes and two analyses but does not explain how they are connected or how their results should be interpreted together. Without analysis definitions and outcome data, readers cannot assess whether estimates represent the intended population or how sensitive they might be to unavailable observations.

Finally, the listed planning assumptions use a two-arm framework, whereas the study is recorded as single group. This illustrates why sample-size planning scenarios should not be mistaken for a description of the trial’s actual design or for evidence about observed power. Overall, the record is statistically useful for understanding the study’s structure, but incomplete for evaluating its clinical outcome evidence.

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 most direct limitation is that the primary MADRS results are not reported in the registry record. Although baseline and 7 weeks are specified, no outcome means, standard deviations, change estimates, or uncertainty measures are available. The primary endpoint’s observed direction, magnitude, and precision therefore cannot be assessed.

The design is single group, with no comparator described and no masking. This prevents a like-for-like control comparison and limits causal interpretation of any change over time. Allocation is recorded as NA. The record does not provide further details about participant eligibility, baseline characteristics, treatment adherence, or individual dosing beyond Depakote ER up to 1500 mg/day.

The registry does not report the analysis population or the number with available observations at each time point. It does not describe missing-data handling, the statistical model, or the method used to analyze measurements across time. The relationship between the two listed outcome measures and two analyses is also unspecified, as is any strategy for multiplicity. These reporting gaps make it difficult to assess the analysis or the reliability of any unreported result.

The stated study purpose includes metabolic and GABA changes assessed using PET and MRI/MRS imaging, but findings for those questions are not reported in the information available. The secondary response outcome is named without a result or detailed definition. Safety reporting is limited to registry counts; serious-event terms are absent, and deaths are not reported in the registry record. The record also does not provide event descriptions or comparative safety data.

These limitations concern the information recorded and the design described. They do not establish that analyses were not conducted or that outcomes were not collected; those details are simply not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Depakote ER in Bipolar Depression — NCT00186186.
• Registry record last updated 2017-04-12; status last verified 2017-03.
• Results first posted 2017-04-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed Phase 4, single-group study of Depakote ER in bipolar depression, sponsored by Stanford University. Enrollment is listed as 28. The intervention is described as Depakote ER up to 1500 mg/day. Allocation is NA, masking is none, and no comparator group is described.

The primary outcome is MADRS, summarized as a continuous measure using a mean and standard deviation, with a timeframe of baseline and 7 weeks. The study purpose also names safety, metabolic and GABA changes, and PET and MRI/MRS brain imaging. A secondary outcome concerns response to Divalproex-ER in acute bipolar 2 depression. The primary and secondary outcome results are not reported in the registry record.

Safety entries record zero serious adverse events among 28 at risk and 3 other adverse events among 28 at risk. Serious-event terms are not listed, and deaths are not reported in the registry record. The record does not describe analysis populations, missing-data handling, or multiplicity methods. Its information supports a description of the study’s structure and planned measures, but not a numerical conclusion about the primary outcome.