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 The Role of Dopamine Metabolism in the Antidepressant Effects of Sleep Deprivation and Sertraline in Depressed Patients (NCT00581009), a randomized phase 1, phase 2 study. The primary outcome is Total Score on the Hamilton Rating Score for Depression (HRSD) - 21 Item Version.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00581009 |
| Phase | Phase 1, Phase 2 |
| Condition | Major Depressive Disorder, Bipolar Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 49 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of California, Irvine |
| Results posted | Yes |
2. Clinical Question
Population
The primary outcome is described for participants with bipolar disorder. The registry record also lists major depressive disorder as a condition and describes an MDD Mechanism arm, but it does not report the primary-outcome analysis population or explain how those participants relate to the stated bipolar-disorder population.
Intervention
The intervention of interest is chronobiological augmentation. The record lists sleep deprivation, bright light therapy, and sleep phase advance in its brief summary, and lists one night of sleep deprivation and two FDG PET scans among the interventions. It does not fully describe the treatment schedule or which participants received each component.
Comparator
The named comparison is chronobiological augmentation versus medication only. Sertraline and lithium are listed as drug interventions. The registry record does not give enough detail to reconstruct the medication regimen in each arm or establish whether medication use was identical between groups.
Primary question
The primary outcome is the total score on the 21-item Hamilton Rating Score for Depression, with scores compared between the chronobiological augmentation and medication-only groups across the first 7 days and up to 7 weeks of treatment. The registry record does not report one numerical estimate for this comparison, so the size and precision of any group difference cannot be assessed from the primary result.
3. Trial Design
This was a randomized, parallel-group study with no masking. The registry lists phase 1 and phase 2 and an enrollment of 49. Its status is completed. The recorded start date is 2001-05-30, and the primary completion date is 2011-12-09. The sponsor is the University of California, Irvine.
The registry names Chronobiological Augmentation, Medication Only, and MDD Mechanism as arms. The MDD Mechanism arm has no description in the record. The main named comparison for the primary outcome is chronobiological augmentation versus medication only. The record lists sertraline and lithium as drug interventions, chronobiological augmentation as another intervention, and one night of sleep deprivation and two FDG PET scans as a radiation intervention. The brief summary also mentions bright light therapy and sleep phase advance. The exact allocation of each treatment component and the timing of each intervention are not reported in the registry record.
Randomization means assignment is intended to make treatment groups comparable on average, although it does not guarantee balance in a particular study. The record does not report the randomization procedure, allocation concealment, or group sizes for the primary outcome analysis. The safety record lists 32 participants at risk in the chronobiological augmentation group and 17 in the medication-only group; these are safety counts and should not automatically be treated as the analysis populations for the primary endpoint.
The study is unmasked, so participants and study personnel were not described as blinded. This may matter when an outcome depends on an assessment process, but the record does not explain who rated the HRSD or what steps were taken to standardize ratings. Detailed protocol procedures and the rationale for the phase designation 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
| Stage | Medication Only Group | Chronobiological Augmentation Group |
|---|---|---|
| STARTED | 17 | 32 |
| Sample Recruitment | 17 | 32 |
| COMPLETED | 17 | 32 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Bipolar disorder subjects
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.
Population: All bipolar depressed subjects
| Characteristic | Unit | Chronobiological Augmentation | Medication Only | Total |
|---|---|---|---|---|
| Participants analysed | 32 | 17 | 49 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 32 | 17 | 49 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 39 (SD 13) | 40 (SD 14) | 39.3 (SD 13.3) |
| Sex: Female, Male: Female | Participants | 10 | 10 | 20 |
| Sex: Female, Male: Male | Participants | 22 | 7 | 29 |
| Region of Enrollment: United States | participants | 32 | 17 | 49 |
6. Primary Endpoint
The registry lists the primary outcome as Total Score on the Hamilton Rating Score for Depression (HRSD) - 21 Item Version, measured over within the first seven days up to 7 weeks (plus or minus 1 day) after sleep deprivation and chronobiological therapy.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Total score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the total score on the 21-item Hamilton Rating Score for Depression (HRSD), a continuous measure. The registry gives its range as 0 to 66 and states that higher scores indicate more severe depression. The stated population for this outcome is bipolar disorder subjects. The measure is intended to quantify depressive symptom severity using the combined item scores.
The registry describes the outcome as a mean score and gives standard deviation as its measure of dispersion. It states that the comparison concerns the chronobiological augmentation and medication-only groups across the first 7 days and up to 7 weeks of treatment, within the timeframe of 7 weeks (plus or minus 1 day) after sleep deprivation and chronobiological therapy. These descriptions do not identify one time point or one group contrast as the sole reported result. The record explicitly indicates that the primary outcome has several categories or time points and was not reduced to one comparison.
In general, a continuous symptom score can show differences in average severity between groups, while the standard deviation describes how spread out individual scores are around the average. A mean difference is interpretable only alongside its direction, size, uncertainty, analysis population, and timing. Those numerical results are not reported in the registry record, so the endpoint definition alone does not establish the direction or magnitude of a group difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies an intended comparison between chronobiological augmentation and medication only, using HRSD total score as the primary outcome. It does not report a single numerical result for that comparison. In particular, a mean difference, confidence interval, and p-value for one clearly defined time point are not reported in the registry record. Therefore, the size, direction, and precision of the primary outcome contrast cannot be assessed from the recorded result.
The registry reports one outcome measure and one analysis, but also indicates that the primary outcome includes several categories or time points and was not reduced to one comparison. Those statements do not reveal which time-specific estimates were calculated or how they were analyzed. A count of analyses is not a substitute for the estimate, its uncertainty, or a description of the analysis population. It is not possible to determine whether a particular time point was selected in advance as the main inferential target.
The brief summary describes the study's aims: evaluating whether sleep deprivation could accelerate antidepressant responses during the first week of medication and whether chronobiological interventions could augment a sustained response. These are statements of purpose, not reported findings. They should not be read as evidence that either outcome occurred. The registry record does not give numerical HRSD results that would support an assessment of those aims.
The record does provide safety counts. For serious adverse events, it lists zero events in each of the two groups. For other adverse events, it lists 2 in the chronobiological augmentation group and 0 in the medication-only group. Deaths are listed as zero in both groups. These are counts, not estimates of comparative risk, and the record does not provide event descriptions or participant-level details. The counts should not be interpreted as proof that an intervention caused or prevented an event.
Enrollment was 49, while the safety counts at risk are 32 and 17. The record does not state whether all enrolled participants contributed primary outcome data, how missing observations were handled, or whether analysis followed randomized assignment. Consequently, the amount of information available for the endpoint and the potential influence of missing data cannot be established. In general, a confidence interval communicates how precisely an estimated contrast is determined under its statistical assumptions; without a reported interval or estimate, precision cannot be judged.
The record's planning assumptions describe illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. They are planning illustrations, not observed power. Numerical planning outputs are not reported in the registry record. Such illustrations cannot replace the missing trial estimate or establish whether the study was adequately powered for its stated outcome.
9. Statistical Methods Explained
The registry describes a randomized, parallel-group design without masking. The primary outcome is continuous and is defined as the mean total HRSD score. The stated dispersion measure is the standard deviation. These labels identify the general form of the outcome summary, but the registry does not report the estimate, the analysis model, or a complete statistical analysis plan.
What does a mean score represent?
In general, a mean is the arithmetic average of the observed scores in a group. A comparison of group means describes an average difference, not the experience of every participant. Individuals may have scores above or below their group average, and a mean alone does not show how much their outcomes overlap. The standard deviation describes the spread of scores around the mean. A larger standard deviation generally indicates more variability among observed scores, while a smaller one indicates scores are more clustered.
For this outcome, interpretation also depends on when scores were collected. The registry describes assessments across the first 7 days and up to 7 weeks, rather than identifying a single time point in the reported result. A mean contrast at one time point can answer a different question from an average contrast across time or a model of change over time. The registry record does not report which summary was used, so no specific repeated-measures approach should be assumed.
What does randomization contribute?
In general, random assignment is used to reduce systematic differences between treatment groups at the start of a study. It supports a comparison of assigned groups, provided the assignment process is implemented appropriately and the analysis preserves the intended comparison. Randomization does not ensure that every prognostic characteristic is balanced in a finite sample. The record states that the study was randomized but does not describe the sequence generation, concealment procedures, or whether the reported analysis followed assignment.
The parallel design means the arms are compared as groups rather than being described as each participant receiving both strategies in sequence. Because masking is listed as none, the study was not described as blinded. In general, lack of masking can affect behavior, co-interventions, reporting, or outcome assessment, depending on how an endpoint is measured. The record does not describe HRSD assessor training, assessor masking, or other procedures that might clarify this concern.
How should uncertainty be considered?
In general, a confidence interval presents a range of values compatible with an estimate under the specified model and assumptions. Its width conveys precision: wider intervals indicate greater uncertainty, while narrower intervals indicate more precision. A p-value addresses how surprising data at least as extreme as those observed would be under a specified null model. It does not measure the size or clinical importance of an effect, and it does not by itself establish that a treatment caused an outcome.
The registry record does not report a single primary mean difference, confidence interval, or p-value. There is therefore no primary estimate whose magnitude or precision can be interpreted. A statement of intended outcome, enrollment, or analysis count cannot substitute for those quantities. Likewise, without the actual analysis specification, it is not possible to assess whether the uncertainty calculation accounted for repeated measurements, baseline values, or other model features.
Why do multiple time points matter?
General statistical practice treats repeated measurements as related observations: scores from the same participant are not necessarily independent. An analysis that accounts for this within-participant relationship can differ from a series of separate comparisons. If numerous time points or outcome categories are examined, the chance of finding an apparently notable result by chance can increase when each is tested independently. Prespecified primary contrasts and suitable multiplicity procedures can help clarify how such evidence should be interpreted. The registry record does not report the analysis strategy or any multiplicity adjustment.
The record lists one outcome measure and one analysis, while also noting that the primary outcome has several categories or time points and was not reduced to one comparison. These statements leave the inferential target unclear. They do not show whether the time points were analyzed jointly, separately, or through a summary measure. No particular model or correction should be inferred from the registry description.
What do the planning assumptions mean?
In general, a sample-size calculation uses assumptions about a target effect, variability, significance level, allocation, and statistical method to illustrate how much information might be required for a planned comparison. The registry states that its planning illustrations were computed from the observed effect and used a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It also says the effect to detect is a stated fraction of the observed effect. Those illustrations are not the trial's design justification, and sample-size calculations are not observed power.
The registry record does not report a sample-size justification for the original study. It does not report a numerical observed effect for the primary outcome in a single comparison, so the planning illustrations cannot be independently interpreted from the result description. A planning calculation based on an observed effect is retrospective and depends on that estimate; it does not show the probability that the study detected a true effect. No numerical planning output is reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry describes the primary outcome across several categories or time points and states that it was not reduced to one comparison. It lists one outcome measure and one analysis, but does not identify a single time-specific contrast as the primary inferential result. The statistical plan for handling repeated measurements, multiple comparisons, or multiplicity is not reported in the registry record. In general, examining multiple outcomes or time points can raise the chance of a false-positive finding if each is treated as an independent test without an appropriate plan. Prespecified contrasts and transparent reporting help readers understand which results were confirmatory and how uncertainty was handled.
Missing-data handling is not reported in the registry record. The number of participants with an observed HRSD score at each assessment, reasons for missing observations, and any imputation or likelihood-based method are not reported. The record also does not state whether participants were analyzed according to their randomized assignment or whether another analysis population was used. Enrollment of 49 does not establish how many participants contributed to each endpoint analysis.
These omissions limit interpretation even if a numerical estimate were available: readers could not judge the role of incomplete follow-up or the relationship between the planned and reported analyses. They also prevent assessment of whether the analysis addressed the correlation among repeated scores. No assumptions about missingness, exclusions, or analytic populations should be inferred from the registry description.
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 |
|---|---|---|---|
| Chronobiological Augmentation | 0 | 32 | 0.0% |
| Medication Only | 0 | 17 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Chronobiological Augmentation | 0 of 32 |
| Medication Only | 0 of 17 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 4% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Chronobiological Augmentation | 2 of 32 |
| Medication Only | 0 of 17 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Chronobiological Augmentation | Medication Only |
|---|---|---|---|
| brief hypomanic switch | Psychiatric disorders | 2 of 32 | 0 of 17 |
The registry lists 32 participants at risk in the chronobiological augmentation group and 17 in the medication-only group. It records zero serious adverse events in each group. For other adverse events, it records 2 in the chronobiological augmentation group and 0 in the medication-only group. Deaths are recorded as zero in both groups.
These are event counts, not a complete account of the nature, timing, severity, or duration of events. The registry record does not list serious adverse event terms, and it does not describe the two other adverse events. It also does not provide an explanation of how events were collected or judged. The figures therefore support only a narrow reading of the reported counts.
In general, an event count alone does not establish whether a treatment caused an event or whether groups differ reliably in safety. Such conclusions require context, including event definitions, follow-up, exposure, and uncertainty. Zero recorded events do not prove that no event could occur. These registry figures should be read as the reported counts for the listed groups, not as a comprehensive safety assessment.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, unmasked, parallel-group study was completed and that its primary outcome concerned HRSD total score in bipolar disorder subjects. It also identifies chronobiological augmentation and medication only as the named comparison. The brief summary describes an interest in accelerating antidepressant response and sustaining response with chronobiological interventions. Those statements explain the study's purpose; they are not results.
The primary outcome does not have a single reported comparison in the registry record. A numerical group difference, its direction, and its precision are not reported. It is therefore not possible to determine from the registry record how the groups compared on HRSD, whether any difference was compatible with no difference, or how stable an estimate might be. No conclusion about treatment benefit or lack of benefit follows from the endpoint description alone.
The safety entries report zero serious adverse events in each group, 2 other adverse events in the chronobiological augmentation group, 0 in the medication-only group, and zero deaths in both groups. Those counts describe the registry entries but do not establish causation or comparative safety. Event descriptions and fuller follow-up information are not reported in the registry record.
In general, a trial result is interpreted using an estimate, uncertainty, study design, outcome timing, and the completeness of follow-up. Here, the registry information available for the primary endpoint does not include a single estimate or uncertainty measure, and it does not describe missing-data handling or the analysis population. The appropriate conclusion is limited: the question and outcome are specified, but the posted primary result does not permit a quantitative assessment of the comparison.
13. Why This Trial Matters Statistically
This study raises a statistically important challenge: the stated clinical question involves change over time, while the registry description does not reduce the primary outcome to one comparison. When measurements are collected repeatedly, the choice of time point or summary matters. Different choices answer different questions, and an analysis should make the target contrast clear enough for readers to interpret the estimate and its uncertainty.
The study is also an example of why a registry entry should distinguish aims from findings. Its brief summary describes the intended role of sleep deprivation and chronobiological interventions in response speed and durability. The primary outcome description names the HRSD and its assessment window, but the registry record does not report a single numerical result. An objective and a measure do not, by themselves, show what the data found.
Unmasked assessment and incomplete reporting of analysis procedures are relevant statistical context. In general, knowledge of treatment assignment can influence participant reporting or ratings, and repeated scores call for clear handling of within-participant dependence. The registry record does not explain how these issues were addressed. It also does not provide missing-data methods or analysis populations, which makes it difficult to assess the reliability and scope of any endpoint inference.
The entry illustrates the value of reporting the treatment contrast, time point, analysis population, estimate, and uncertainty together. Without those details, enrollment and planning assumptions cannot establish the precision of the primary comparison. The safety counts remain useful as recorded event totals, but they are not a substitute for a detailed safety analysis or the primary outcome result.
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 statistical interpretation is that the registry record does not report one numerical primary-outcome comparison. Although it names a continuous HRSD score and a treatment comparison across the first 7 days and up to 7 weeks, it indicates that the outcome has several categories or time points and was not reduced to one comparison. The analysis model, time-specific estimates, confidence intervals, and p-values are not reported in the registry record.
The stated primary-outcome population is bipolar disorder subjects, while the listed conditions include major depressive disorder and bipolar disorder, and an MDD Mechanism arm appears in the arm descriptions. The relationship between that arm and the primary-outcome population is not explained. The record does not report the primary analysis sample size or clarify which arms contributed to it. Safety group counts should not be assumed to define the endpoint populations.
Intervention detail is limited for reconstructing the comparison. The registry lists sertraline, lithium, chronobiological augmentation, and one night of sleep deprivation and two FDG PET scans; its brief summary also names bright light therapy and sleep phase advance. The exact schedule, medication use by arm, and allocation of components are not reported in the registry record. This limits the ability to identify precisely what differed between groups.
The record does not describe the randomization procedure, allocation concealment, HRSD assessment procedures, missing-data handling, analysis populations, or multiplicity strategy. It also provides little detail about adverse events beyond the recorded counts. These omissions do not establish that procedures were inadequate, but they constrain what can be evaluated from the registry information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Role of Dopamine Metabolism in the Antidepressant Effects of Sleep Deprivation and Sertraline in Depressed Patients — NCT00581009.
- Registry record last updated 2024-10-17; status last verified 2024-10.
- Results first posted 2024-10-17.
- 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
NCT00581009 is a completed, randomized, unmasked, parallel-group phase 1 and phase 2 study sponsored by the University of California, Irvine. Enrollment was 49. The registry lists major depressive disorder and bipolar disorder and names Chronobiological Augmentation, Medication Only, and MDD Mechanism arms.
The primary outcome is mean total score on the 21-item HRSD, with standard deviation as the stated measure of dispersion. The score ranges from 0 to 66, with higher scores indicating more severe depression. The stated primary-outcome population is bipolar disorder subjects, and the described comparison is chronobiological augmentation versus medication only across the first 7 days and up to 7 weeks.
The registry record does not report a single primary comparison result, and it does not report the analysis methods, missing-data approach, or analysis populations. Safety counts list zero serious adverse events in each comparison group, 2 other adverse events in the chronobiological augmentation group, 0 in the medication-only group, and zero deaths in both groups.