This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Lamotrigine Monotherapy in Pediatric Bipolar Disorder (NCT00176228), a na phase 2 study. The primary outcome is Young Mania Rating Scale (YMRS),.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00176228 |
| Phase | Phase 2 |
| Condition | Bipolar Disorder |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 48 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Illinois Chicago |
| Results posted | Yes |
2. Clinical Question
Population
Children and adolescents aged 8–17 with bipolar disorder were the intended population. The study description specifies that participants had to be treatment resistant, defined as having failed two adequate trials of mood-stabilizing medications. The record does not report further eligibility details or the characteristics of the enrolled participants.
Intervention
The intervention was lamotrigine monotherapy. The study description focuses on mood stabilization across mixed, manic, hypomanic, or depressed episodes. Treatment included an 8 week dose-titration phase and a 6 week full-dose phase; additional details about the regimen are not fully reported in the registry record.
Comparator
There was no separate comparator group. The study is described as open and single-group, with no masking and no randomized allocation. Its structure therefore does not provide a like-for-like control group for estimating how outcomes would have changed without lamotrigine.
Primary question
The primary outcome was the Young Mania Rating Scale (YMRS), recorded as a mean score. The planned measurements were weekly during treatment, with means and standard deviations specified at week 0, week 8, and week 14 to indicate possible change over the study period. The actual YMRS results and any estimate of change are not reported in the registry record.
The study also had a stated brain-activity objective: to examine activity or dysfunction before treatment and look for alteration after treatment in systems associated with attention and emotional processing. The record does not provide findings for that objective. A Child Depression Rating Scale (CDRS-R) measure is listed as a secondary outcome, but its results are not reported in the registry record.
3. Trial Design
This was a phase 2, open-label, single-group study of lamotrigine monotherapy. The registry record lists enrollment of 48 and identifies bipolar disorder as the condition. There was no randomized allocation, no masking, and no parallel control group. The study was sponsored by University of Illinois Chicago, with a start date of 2004-02 and primary completion in 2008-01; its status is completed.
The planned treatment period included an 8 week lamotrigine dose-titration phase followed by a 6 week full-dose phase. The primary YMRS measurement timeframe is described as weekly during these phases. Means and standard deviations at week 0, week 8, and week 14 were specified as a way to assess score change. The registry record does not report the actual score summaries at those time points, the number of participants contributing data at each time, or the method used to compare measurements over time.
The study description gives two purposes: assessing safety and efficacy across phases of pediatric bipolar disorder, and examining brain activity before and after treatment. The registry record does not report results for the brain-activity objective. The listed secondary outcome is the CDRS-R, but its results are also not reported.
Because the design has no control group, it can describe observed outcomes among participants receiving the intervention if those data are reported, but it cannot by itself separate treatment-associated change from other influences over time. The record does not report the protocol’s statistical plan, a sample-size justification, interim analyses, or details of participant flow. The stated enrollment is not a substitute for those missing design and analysis details.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: To participate, subjects were required to consent to being washed out of their current medications at study entry. The washout period consisted of tapering their previous medications over one week prior to study entry except for those who received aripiprazole or fluoxetine who required a 4-week washout period.
Overall Study
| Stage | Lamotrigine |
|---|---|
| STARTED | 48 |
| COMPLETED | 46 |
| NOT COMPLETED | 2 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Lamotrigine |
|---|---|---|
| Participants analysed | 48 | |
| Age, Categorical: <=18 years | Participants | 48 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 13.3 (SD 2.85) |
| Sex: Female, Male: Female | Participants | 27 |
| Sex: Female, Male: Male | Participants | 21 |
| Region of Enrollment: United States | participants | 48 |
6. Primary Endpoint
The registry lists the primary outcome as Young Mania Rating Scale (YMRS),, measured over Weekly during the 8 week lamotrigine dose titration and 6 week full dose phase..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the Young Mania Rating Scale (YMRS), a continuous measure of manic symptom severity. The record describes 11 items, each rated according to symptom severity using the participant’s report of the previous forty-eight hours and the clinician’s behavioral observations, with emphasis on the latter. Four items use a 0 to 8 scale and the remaining seven use a 0 to 4 scale. The total can range from zero to 60, with zero described as normal and 60 as severe; a score of 12 or above is described as a cutoff point for illness.
A continuous score can represent changes across a range of symptom severity rather than reducing the measurement to a simple category. The registry record specifies the mean and standard deviation at week 0, week 8, and week 14 as indicators of change during treatment. Those summaries could describe the group’s average scores and the spread of scores around that average, but the actual values are not reported in the registry record. No endpoint estimate, uncertainty interval, or formal test of change is reported.
The CDRS-R is listed as a secondary outcome. Its measurement details and results are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study’s intended question and measurement schedule, but it does not give the YMRS results needed to judge the direction, size, or precision of any change. Although means and standard deviations at week 0, week 8, and week 14 are specified, those values are not reported in the registry record. A numerical estimate of change, a confidence interval, and a statistical test are also not reported. It is therefore not possible to determine from this record how scores changed during treatment or how uncertain any estimated change would be.
The design also limits what a change over time could establish, even if score summaries were available. Participants received the intervention in an open, single-group study, without randomization, masking, or a control group. In general, an observed change in a single group can reflect multiple influences, including the course of symptoms over time, expectations, measurement conditions, or other care. Without a control group, the study cannot isolate the contribution of lamotrigine from those possibilities. Open treatment can also affect reporting or rating, particularly when outcomes include clinician judgments.
The YMRS is a severity measure with a total range from zero to 60. The record describes 12 or above as a cutoff point for illness, but no participant scores or distributions are reported. The cutoff description alone does not establish how many participants met that threshold, whether scores crossed it during the study, or whether any change was clinically meaningful. Those quantities are not reported in the registry record.
The registry lists enrollment of 48, but does not report how many participants contributed YMRS measurements at each planned time point or how missing observations were handled. Enrollment therefore cannot be treated as the denominator for every outcome summary. The record also lists 0 analyses and does not report an analysis method, adjustment strategy, or uncertainty estimate. No inferential conclusion can be reconstructed from the design description alone.
Serious adverse event reporting lists 0 affected among 48 at risk for the lamotrigine group. That is a registry-reported count, not a complete account of adverse effects or proof that no safety events occurred beyond those captured by the listed measure. Other adverse events are separately listed as 0 affected among 48 at risk. Details of ascertainment and completeness are not reported.
9. Statistical Methods Explained
The primary outcome is continuous: the YMRS total score. A mean describes the arithmetic center of the recorded scores, while a standard deviation describes how spread out individual scores are around that mean. These summaries answer different questions. A mean can indicate the group’s average score at a time point; a standard deviation conveys variation among scores, not the precision of the mean itself.
In general, uncertainty about an estimated mean or change is often expressed with a confidence interval. A confidence interval describes a range of values compatible with the data under the method’s assumptions. It is not the same as the standard deviation, and it does not by itself establish clinical importance. No confidence interval for the YMRS, or for change between the stated time points, is reported in the registry record.
The planned time points are week 0, week 8, and week 14. In general, repeated measurements from the same participants are related rather than independent: a participant’s scores over time may be more alike than scores from different participants. Analyses of repeated measurements can account for that within-participant relationship, but the statistical method used for this study is not reported in the registry record. The planned weekly measurement timeframe also does not establish that all participants completed every weekly assessment.
In general, a change in group mean can be described as an average change, but it may conceal different individual trajectories. Some participants may have higher scores and others lower scores, while the group average changes little; conversely, an average shift does not mean that every participant changed by the same amount. The registry record does not report individual-level outcomes, distributions, or the number of participants with complete measurements at each time point.
The record describes a YMRS total from zero to 60 and a cutoff point of 12 or above. A threshold can support a categorical description, but it discards information about distances between scores. The registry record does not report a threshold-based analysis, participant counts above or below the cutoff, or how the cutoff was used in statistical analysis. The stated primary endpoint is a mean, not a reported binary outcome.
There is no randomized comparison in this study. General methods for comparing a treatment group with a concurrent control group are not applicable as direct descriptions of the enrolled design. A before-and-after comparison within the single group, if performed, would describe change over time among observed participants; it would not supply the counterfactual outcome those participants might have experienced without treatment. The registry record does not identify whether such a comparison was formally conducted.
The record’s planning assumptions describe a hypothetical sample-size illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. Those assumptions do not match the actual single-group design. Such planning illustrations are not observed power and do not provide evidence about treatment effect or the precision achieved in this study. The record does not report the trial’s own sample-size justification or numerical planning results.
Over-dispersion is a general issue for count outcomes when variability exceeds what a simple probability model expects. It is not a direct feature of the primary endpoint here, which is a continuous YMRS score, and the record does not identify a count-based primary analysis. More generally, the choice of statistical model should match the outcome scale, measurement schedule, and data structure. The model and its assumptions are not reported in the registry record.
Formal hypothesis tests, if used, would need to be interpreted alongside estimates and uncertainty rather than as a stand-alone measure of importance. A p-value describes how compatible data are with a specified null model under the test’s assumptions; it is not the probability that a treatment effect is true. No p-value or formal test result is reported in the registry record. The registry also lists 0 analyses, so the record does not provide an analysis output from which a test or model can be assessed.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies the YMRS as the primary outcome and the CDRS-R as a secondary outcome. It also describes a brain-activity objective involving assessment before and after treatment. These multiple outcomes and objectives create the general possibility of multiplicity: when many outcomes, time points, or analyses are examined, the chance of at least one apparently notable result can increase. Whether and how that issue was addressed is not reported in the registry record.
The primary YMRS timeframe includes weekly measurements during the 8 week titration and 6 week full-dose phases, while the description highlights means and standard deviations at week 0, week 8, and week 14. The record does not specify which comparisons were designated for formal inference, whether other time points were analyzed, or whether any adjustment for multiple testing was planned. The statistical analysis plan is not reported in the registry record.
Missing-data details are also not reported. The record does not state how many participants had outcome data at each time point, why any measurements may have been missing, or how missing values were handled. It does not identify an analysis population, such as all enrolled participants or participants with observed measurements. Enrollment of 48 alone does not establish the number included in any outcome analysis.
The registry lists 0 analyses. It therefore does not report model specifications, methods for handling repeated measures, sensitivity analyses, or an approach to missing data. These omissions prevent assessment of whether the reported analysis, if any, preserved the planned outcome definition or addressed incomplete follow-up. The actual YMRS and CDRS-R results are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Lamotrigine | 0 | 48 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Lamotrigine | 0 of 48 |
For the lamotrigine group, the registry record lists 48 at risk and 0 affected for serious adverse events. It lists 48 at risk and 0 affected for other adverse events. These are the figures recorded for those categories; they should be read as reported counts, not as a comprehensive account of every possible safety outcome.
The record does not provide the adverse-event collection methods, event definitions, surveillance schedule, or information about completeness of reporting. It also does not report a serious adverse event term among the listed top terms. Deaths are recorded as null, so death information is not reported in the registry record. A zero count in the listed affected field does not resolve the absence of these additional details, nor does it describe event severity or timing.
Because this is a single-group study, the safety figures do not provide a randomized comparison of event rates. The listed at-risk count should not be assumed to apply to every outcome or follow-up period unless the registry specifies that. No such period-specific denominator is reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record describes a phase 2 study of lamotrigine monotherapy in children and adolescents aged 8–17 with treatment-resistant bipolar disorder. It identifies the YMRS as the primary continuous outcome, describes its scoring, and specifies planned assessment during titration and full-dose treatment. It also records enrollment of 48 and lists a CDRS-R secondary outcome.
Those details establish what the study set out to examine, but not what the outcomes showed. The YMRS means and standard deviations at the specified time points are not reported in the registry record. Neither a change estimate nor its uncertainty is reported. The CDRS-R and brain-activity findings are also not reported. Consequently, this record does not support a quantitative conclusion about changes in mania ratings, depression ratings, or brain activity.
Even if a within-group score change were available, the open, single-group design would not establish that the change was caused by lamotrigine. Without randomization and a control group, time-related changes, expectations, measurement effects, or other influences cannot be separated from the treatment experience. This is a general limitation of interpreting uncontrolled before-and-after observations, not a claim that any particular influence occurred in this study.
The serious adverse event listing records 0 affected among 48 at risk, and the other adverse event listing also records 0 affected among 48 at risk. The registry record does not describe ascertainment or completeness, and deaths are not reported. These entries therefore describe the registry’s listed counts without establishing a complete safety profile.
Overall, the record is informative about the intended population, design, and outcome definitions. It does not provide enough outcome or analysis information to estimate efficacy, assess statistical precision, or draw a comparative safety conclusion.
13. Why This Trial Matters Statistically
This trial is statistically notable for the gap between a clearly described clinical measurement and the absence of its reported results in the registry record. The YMRS is defined as a continuous score, its scale and cutoff are described, and a schedule for assessment is stated. Yet the means and standard deviations intended to indicate change are not reported. Without those values, readers cannot evaluate the magnitude or variability of observed scores.
The single-group design also illustrates why design structure matters for interpretation. A group’s scores can be followed over time, but without a concurrent comparator, a change cannot be separated from other changes occurring during the same period. The open design adds a general possibility that knowledge of treatment or expectations could influence reports or ratings. These limitations do not mean that the study’s observations would be uninformative; they define what those observations could establish.
The registry also identifies a secondary symptom measure and a brain-activity objective. When several outcomes or time points are relevant, a prespecified analysis plan helps readers understand which questions are confirmatory and how multiple comparisons are handled. Such a plan is not reported in the registry record, nor are outcome analyses reported.
Finally, the listed serious adverse event count is a descriptive entry, not a substitute for detail about ascertainment, timing, or completeness. Taken together, the record demonstrates how design, outcome reporting, and analysis details are all needed to move from a study question to an interpretable estimate. The intended question is identifiable; the statistical evidence needed to quantify its answer is not reported.
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 principal limitation for interpreting this trial record is that it does not report the primary YMRS results. The planned means and standard deviations at week 0, week 8, and week 14 are not available in the registry record, and no estimate of change, confidence interval, or test result is reported. Results for the listed secondary CDRS-R outcome are also not reported.
The study’s open, single-group design has no randomized comparator and no masking. It therefore cannot provide a like-for-like comparison with a group not receiving lamotrigine. Any within-group change, if available, could not by itself distinguish treatment-associated change from other influences over time. The registry record does not report details that would permit assessment of concomitant care or other time-varying influences.
Participant-flow information and outcome-specific denominators are not reported. Although enrollment is listed as 48, the record does not say how many participants completed each assessment or how missing observations were handled. The analysis population and statistical model are not reported, and the registry lists 0 analyses. The statistical plan, multiplicity approach, and sample-size justification are also not reported in the registry record.
The record describes the study’s intended age range and treatment-resistance requirement, but does not report enrolled-participant characteristics. This limits assessment of how closely the analyzed population, if any, matched the intended population. The brain-activity objective is stated without reported findings. Safety entries lack detail on ascertainment and completeness, and death information is not reported.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Lamotrigine Monotherapy in Pediatric Bipolar Disorder — NCT00176228.
- Registry record last updated 2015-07-30; status last verified 2015-06.
- Results first posted 2015-07-30.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
This completed phase 2 study evaluated lamotrigine monotherapy in a planned population of children and adolescents aged 8–17 with treatment-resistant bipolar disorder. It was open and single-group, with no randomized allocation or masking, and listed enrollment of 48. The primary outcome was the YMRS mean score, with measurements planned during an 8 week titration phase and a 6 week full-dose phase. The CDRS-R was listed as a secondary outcome.
The registry record does not report the YMRS or CDRS-R results, a statistical analysis, or findings for the brain-activity objective. It lists 0 affected among 48 at risk for serious adverse events and 0 affected among 48 at risk for other adverse events; deaths are not reported. The record identifies the study question and design but does not provide outcome estimates or their statistical uncertainty.