Personalized Therapeutic Neuromodulation for Anhedonic Depression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Personalized Therapeutic Neuromodulation for Anhedonic Depression (NCT05144789), a randomized na study. The primary outcome is Percentage Change in MADRS Score.

2. Clinical Question

The clinical question concerns depressive symptom scores, with particular interest in the study summary’s stated focus on anhedonia. The listed primary endpoint, however, is percentage change in the overall MADRS score. The registry description says the scale is designed to be particularly sensitive to antidepressant treatment effects in patients with major depression. It does not describe a separate primary anhedonia measure in the information available.

The randomized design sets up comparisons involving two active stimulation targets and a sham condition. Whether each active target differed from sham, whether the active targets differed from each other, and how such comparisons were handled statistically are not reported in the registry record. No conclusion about the direction or size of those differences can be drawn from the outcome description alone.

3. Trial Design

The registry describes a randomized, quadruple-masked, parallel trial sponsored by Stanford University. The condition listed is treatment-resistant depression, and the study summary states that it investigates the anti-anhedonic efficacy of accelerated intermittent theta burst stimulation. The record lists 70 participants enrolled. Its status is completed, with a start date of 2022-05-31 and a primary completion date of 2025-06-06.

Three intervention groups are listed: Active TBS-DLPFC, Active TBS-DMPFC, and Sham TBS-DLPFC or DMPFC. The two active groups are described as receiving theta-burst TMS stimulation; the sham group is described as receiving sham theta-burst TMS stimulation. The registry classifies the interventions as devices. The treatment descriptions do not report enough detail to reconstruct stimulation schedules, treatment dose, allocation ratios, or which sham target corresponded to each active group. Those details are not reported in the registry record.

Randomization means the trial used an assignment process intended to allocate participants among groups by chance. Masking is intended to limit the influence of knowledge about assigned treatment on trial conduct or assessment. The record labels masking quadruple but does not identify which roles were masked or describe how masking was maintained. A parallel design means the listed groups are compared as separate groups rather than as treatment periods experienced by the same participants.

The registry lists phase as NA. It also lists two outcome measures, while no statistical analyses are listed. The primary endpoint is a continuous measure summarized as a mean with standard deviation. The primary analysis population is described as participants who completed the protocol. The registry does not report the number in that population, the allocation counts for all groups, or the analysis methods used for the primary endpoint.

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: Two participants who completed screening withdrew prior to assignment to a study arm.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Participants who completed the protocol

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: Participants who completed the protocol

6. Primary Endpoint

The registry lists the primary outcome as Percentage Change in MADRS Score, measured over Baseline, immediate post treatment (up to 2 weeks post baseline), 4 weeks and 8 weeks post treatment..

The primary endpoint is percentage change in MADRS score. The MADRS is described in the registry as a 10-item self-survey administered scale designed to be particularly sensitive to antidepressant treatment effects in patients with major depression. Its score range is 0 to 54, with higher scores corresponding to more severe depressive symptoms.

Using change from baseline focuses attention on how scores differ from participants’ starting measurements rather than relying only on scores at a later assessment. Expressing change as a percentage can place the change in relation to the baseline score. The registry does not state the formula used to calculate percentage change, how scores were handled when a baseline value was zero, or how the endpoint was summarized across assessment times. These details are not reported in the registry record.

The listed timeframe includes baseline, immediate post treatment (up to 2 weeks post baseline), 4 weeks and 8 weeks post treatment. This means the primary endpoint is associated with multiple assessment points; it is not a single measurement at one follow-up time. The registry does not identify one assessment time as the sole primary comparison or explain how the multiple time points were incorporated into an analysis.

The scale provides a measure of depressive symptom severity, not a direct account of every aspect of anhedonia. The study summary describes an anti-anhedonic aim, but the registry’s primary-outcome description is the percentage change in MADRS score. Without posted outcome estimates, the record does not show how scores changed or how precisely any group differences were estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

General statistical explanation: A mean is a measure of the center of a set of measurements. A standard deviation describes how dispersed individual measurements are around that mean. For a continuous endpoint such as percentage change in MADRS score, these summaries can describe the average observed change and the variability among participants. A standard deviation is not the same as a confidence interval: it describes variation in the observations, whereas a confidence interval expresses uncertainty about an estimated quantity.

The registry specifies the mean and standard deviation as the summary form for the primary endpoint. It does not report the numerical summaries, the number of observations contributing to them, or whether the same summary approach was used at every listed assessment time. Thus, the endpoint’s intended summary can be described, but its observed distribution and uncertainty cannot be evaluated.

How should a treatment contrast be read?

General statistical explanation: A treatment contrast expresses the estimated difference between groups on a defined outcome and at a defined assessment. It should be read together with its unit, the groups being compared, and the uncertainty around the estimate. A confidence interval gives a range of values compatible with the data and analysis under the method’s assumptions. A narrower interval indicates greater precision than a wider interval, but it does not by itself establish clinical importance.

No primary-outcome contrasts or confidence intervals are reported in the registry record. The listed outcome has multiple time points, and the record does not identify one as the single comparison for interpretation. There is therefore no posted estimate whose size or precision can be explained. The endpoint description alone does not indicate whether observed scores favored an active group, sham, or neither.

Why do multiple time points and groups matter?

General statistical explanation: When a study makes several comparisons, there are more opportunities for an apparently unusual result to occur by chance. Statistical methods may address this multiplicity by defining a primary comparison in advance, adjusting inference across comparisons, or using a model that accounts for repeated measurements. These approaches answer different questions and can affect how uncertainty is interpreted.

The record lists two active stimulation groups, a sham group, and several assessment times. It does not report the analysis plan or how comparisons across groups and times were handled. The registry indicates that the primary outcome has several categories or time points and is not reduced to one comparison. Any multiplicity adjustment or prespecified hierarchy is not reported in the registry record.

What does the sample-size illustration represent?

General statistical explanation: A sample-size calculation is a planning exercise that estimates how many participants might be needed to detect an effect under chosen assumptions. It is not a result of the trial and should not be read as evidence that an effect was observed. A calculation based on an observed effect can be especially sensitive to uncertainty in that effect estimate; a planning illustration is not a substitute for the actual treatment estimate and its confidence interval.

The registry’s stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. The registry labels this as a planning illustration rather than the trial’s own design. The actual effect estimate, the fractions used, and the resulting planning counts are not reported in the registry record. These calculations should not be interpreted as observed power.

Why can over-dispersion matter?

General statistical explanation: Over-dispersion occurs when the variability in data is greater than a statistical model expects. If a model underestimates variability, its uncertainty estimates may be too small, which can make results appear more precise than warranted. The relevance of over-dispersion depends on the outcome and model; it is not a universal adjustment. The primary outcome is described as continuous and summarized using a mean and standard deviation. The registry does not report a fitted model or any assessment of over-dispersion, so it is not possible to say whether that issue was relevant to the actual analysis.

The record lists no analyses. It also does not report the model used for repeated measurements, how baseline scores entered the analysis, how missing observations were handled, or whether adjusted estimates were calculated. Those decisions can affect both the estimated contrast and its uncertainty. Because they are not reported in the registry record, the analysis cannot be independently evaluated from the posted information.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is measured at baseline, immediately post treatment (up to 2 weeks post baseline), 4 weeks and 8 weeks post treatment. The record also lists two active stimulation groups and a sham group. This creates potential choices about which group comparisons and assessment times to emphasize. The registry notes that the primary outcome has several categories or time points and is not reduced to one comparison. A prespecified primary contrast, multiplicity procedure, or hierarchy among assessments is not reported in the registry record.

Multiplicity matters because repeated statistical testing can increase the chance of at least one result appearing notable by chance. General statistical explanation: A study may address this by adjusting significance thresholds, controlling a family-wise error rate, or defining a limited primary comparison and treating others as secondary or exploratory. The appropriate approach depends on the trial question and plan. No such approach is listed in the record, and no outcome analyses are reported.

The primary population is described as participants who completed the protocol. The record does not give the number of completers, identify an intention-to-treat analysis population, or report how missing endpoint measurements were handled. It also does not report reasons for non-completion or whether the analysis included participants with incomplete follow-up. These omissions limit assessment of how closely the analyzed population may represent all randomized participants.

General statistical explanation: Missing data can affect estimates when the chance of a measurement being missing is related to participant characteristics or outcomes. Complete-case analyses can be biased under some missingness patterns, while imputation or model-based methods rely on assumptions that also need evaluation. Since the registry does not describe the analysis approach or missingness, the consequences for the primary result cannot be assessed.

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 0% reporting threshold.

The registry lists serious adverse events, other adverse events, and deaths separately for the three groups. For Active TBS-DLPFC, 23 participants were at risk for serious and other events; the recorded affected counts were 0, and deaths were 0. For Active TBS-DMPFC, 23 participants were at risk for serious and other events; the recorded affected counts were 0, and deaths were 0. For Sham TBS, 22 participants were at risk for serious and other events; the recorded affected counts were 0, and deaths were 0. No serious adverse-event terms are listed.

These are counts as recorded, not percentages or adjusted comparisons. The registry does not report the event-collection period, definitions used for the listed categories, or whether the at-risk counts represent every participant randomized to each group. The zero counts should therefore be read as the posted safety entries, not as a complete description of all possible safety outcomes or as proof that no events occurred outside the reporting scope.

With no serious-event terms listed and zero recorded affected counts, the registry does not allow comparison of event rates over a specified follow-up period or evaluation of differences between groups. The safety entries do not establish the efficacy of an intervention. Further detail about safety monitoring and the analysis of adverse events is not reported in the registry record.

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

The record establishes that a randomized, quadruple-masked, parallel study of active TBS at two targets and sham stimulation was completed. It identifies a primary endpoint based on percentage change in MADRS score and specifies an analysis population of participants who completed the protocol. It also posts group-level safety counts. These details define what the study set out to compare and how its primary outcome was described.

The record does not report primary-outcome means, standard deviations, group contrasts, confidence intervals, or p-values. Consequently, it does not show the amount or direction of change in MADRS score, whether the groups differed, or how precisely any difference was estimated. No efficacy conclusion can be drawn from the endpoint title or the trial’s completed status.

The primary endpoint is a symptom-scale outcome, while the study summary describes an interest in anti-anhedonic efficacy. A result on the listed scale would need to be interpreted as a result on that endpoint; it should not automatically be taken as a direct measurement of every feature of anhedonia. The registry does not report additional outcome details that would allow a broader interpretation.

Likewise, the safety entries are limited to the recorded counts and at-risk participants. They do not report event timing, detailed definitions, or comparisons adjusted for exposure or follow-up. The absence of listed serious-event terms does not establish that every possible safety outcome was assessed or that the interventions have a particular safety profile.

In short, the registry record documents a trial design and selected outcome and safety information, but not analyzed primary results. Interpretation of treatment differences, uncertainty, clinical relevance, missing data, or multiplicity would require statistical results and methodological details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial raises a statistical question that is important for studies with multiple treatment groups and repeated outcome assessments: the definition of the comparison needs to be clear. The registry lists two active stimulation targets, a sham group, and several assessment times for the primary outcome. Without a reported primary contrast or analysis plan, readers cannot tell which estimate was intended to carry the main inferential weight.

The endpoint also illustrates the distinction between naming a measure and reporting a result. Percentage change in MADRS score specifies the type of outcome, while the mean and standard deviation specify intended descriptive summaries. Neither tells readers the observed effect, its variability, or its precision. Those quantities are needed to evaluate the evidence rather than merely the design.

The stated analysis population—participants who completed the protocol—makes reporting of participant flow and missing measurements especially relevant. The registry record does not give the number of completers or explain how incomplete assessments were treated. Such information helps readers assess whether the analysis reflects the randomized groups and whether follow-up could affect interpretation.

The safety entries are also a reminder that event counts need context. Counts without a reported observation period, definitions, or detailed collection methods have a limited interpretive scope. Together, these features show why transparent reporting of outcome estimates, uncertainty, analysis populations, and methods is necessary for evaluating a completed clinical trial.

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 central limitation of the registry record is that it does not report analyzed primary-outcome results. The endpoint is specified, but numerical group summaries and treatment contrasts are not. Its direction, size, and precision therefore cannot be assessed. The record lists two outcome measures, but details beyond the primary endpoint are not reported in the registry record.

The primary endpoint spans several assessment times, and the registry does not identify a single primary time point or explain how the repeated measurements were analyzed. It does not report a multiplicity strategy, model specification, baseline adjustment, or any sensitivity analyses. No statistical analyses are listed.

The primary analysis population consists of participants who completed the protocol, but the number of completers and their relationship to the randomized population are not reported. The record does not describe missing-data patterns, reasons for non-completion, or methods for handling incomplete assessments. This limits assessment of potential selection or missing-data effects.

Intervention descriptions identify the active target regions and sham stimulation, but do not provide treatment schedules, dose details, allocation counts for the complete randomized groups, or the pairing of sham targets with active groups. The quadruple-masking label is not accompanied by a description of who was masked or how masking was maintained.

Safety information is limited to the listed at-risk and affected counts, deaths, and absence of serious-event terms. The event observation period and detailed collection methods are not reported. These limitations concern what can be interpreted from the registry record and do not establish that the trial itself lacked methods or data that were not posted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Personalized Therapeutic Neuromodulation for Anhedonic Depression — NCT05144789.
• Registry record last updated 2026-07-29; status last verified 2026-07.
• Results first posted 2026-07-29.
• 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

NCT05144789 is a completed randomized, quadruple-masked, parallel study sponsored by Stanford University. It lists 70 enrolled participants with treatment-resistant depression and compares active TBS directed to the DLPFC or DMPFC with sham TBS. The registry lists phase as NA.

The primary endpoint is percentage change in MADRS score among participants who completed the protocol, assessed at baseline, immediately post treatment (up to 2 weeks post baseline), 4 weeks and 8 weeks post treatment. The registry does not report primary-outcome estimates or statistical analyses, and it notes that the outcome has several categories or time points rather than one reduced comparison.

Safety entries list zero serious events, zero other events, and zero deaths in each group; the listed at-risk counts are 23, 23, and 22. No serious adverse-event terms are listed. Further outcome, analysis, missing-data, and safety-collection details are not reported in the registry record.