Anhedonia, Development, and Emotions: Phenotyping and Therapeutics: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Anhedonia, Development, and Emotions: Phenotyping and Therapeutics (NCT05487885), a non-randomized phase 4 study. The primary outcome is Montgomery-Asberg Depression Rating Scale (MADRS) Score.

2. Clinical Question

3. Trial Design

The ADEPT Study is a completed Phase 4 study with non-randomized allocation, no masking, and a sequential model. It enrolled 123 participants and addressed depression and anhedonia. The registry lists a start date of 2022-07-22 and a primary completion date of 2024-12-19. Its stated goal was to understand anhedonia in young people and how it changes with treatments targeting the brain circuit underlying it.

The study description presents two phases. Phase 1 involved a set of assessments, including MRI scans, blood draws, behavioral tasks, clinical interviews, questionnaires, and app-based assessments of experiences and behaviors. Phase 2 involved therapeutic activities, including TMS, Positive Affect Training, and ketamine for some participants. The registry says that participants who qualified and were interested could choose to undertake Phase 2 activities in addition to Phase 1.

The listed interventions are continuous theta burst stimulation, Positive Affect Training, and ketamine injectable solution. The intervention descriptions identify two open-label pathways: TMS and PAT, and TMS and PAT followed by ketamine. There was no randomization to placebo. The registry therefore does not describe a randomized trial in which assigned treatment groups can be interpreted as exchangeable at baseline. The treatment pathways also do not constitute a like-for-like control comparison.

For the primary outcome, 50 participants initiated TMS. Forty-eight had evaluable pre- and post-TMS MADRS data and were analyzed; two discontinued before assessment. Twenty-four participants subsequently completed ketamine with evaluable pre- and post-ketamine MADRS data. The primary-outcome analyses were restricted to Phase 2 participants, with no more than 50 participants. These pathway-specific numbers describe the available analysis populations, not the full enrollment across both phases.

The sample-size illustrations displayed elsewhere on the page are planning exercises, not the study's enrollment target or observed power. The registry record does not report the study's sample-size justification or a fuller statistical analysis plan.

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.

Phase 1

Reasons for not completing this period:

TMS and PAT

Reasons for not completing this period:

Ketamine

Analysis population for the primary outcome, as defined in the registry: Fifty participants initiated TMS; 48 had evaluable pre- and post-TMS MADRS data and were analyzed; two discontinued prior to assessment. Twenty-four subsequently completed ketamine with evaluable pre- and post-ketamine MADRS data. Analyses were restricted to Phase 2 participants (N≤50).

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) Score, measured over pre- to post-TMS (over 2 weeks) and pre- to post-ketamine (24 hours).

The primary endpoint is the Montgomery-Asberg Depression Rating Scale (MADRS) score, a clinician-rated measure of depression severity. The registry describes a scale from 0 to 60, with higher scores reflecting greater severity. The outcome is a mean score, with standard deviation as its measure of dispersion.

The registry gives two assessment windows: pre- to post-TMS over 2 weeks and pre- to post-ketamine at 24 hours. Repeated assessment of the same person can describe how the measured score differs across those times. In general, a clinician-rated symptom scale gives a structured way to summarize severity, while reporting both a mean and a standard deviation describes the group average and the spread of participant scores around it.

The endpoint is useful for describing symptom measurements, but a score change alone does not establish why a change occurred. In this study, treatment was not randomized and there was no placebo assignment. A before-and-after pattern can reflect multiple influences, and it is not equivalent to a causal estimate from a randomized comparison.

The posted registry record does not include the actual MADRS means, standard deviations, changes, confidence intervals, or test results. Consequently, the endpoint definition and timing are clear, but the magnitude and precision of the posted outcome cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is continuous: MADRS is recorded as a score, and the registry describes the primary parameter as a mean with standard deviation. In general, a mean summarizes the center of a set of scores, while a standard deviation describes how spread out individual scores are around that mean. Neither measure alone describes the uncertainty in a mean estimate. A confidence interval, when reported, gives a range of values compatible with the data and the chosen method; it is not a guarantee that the true value lies in that range.

What does a before-and-after analysis describe?

For the TMS period, the registry identifies measurements before and after treatment over 2 weeks. For the ketamine period, it identifies measurements before and after treatment at 24 hours. In general, comparing two measurements from the same participant can account for the fact that those measurements are paired. The difference between a participant's two scores is distinct from comparing two unrelated groups. A group mean difference in paired scores can summarize average within-person change, but it does not by itself establish that treatment caused the change.

The registry record does not report the specific statistical test, model, adjustment variables, or method for estimating uncertainty. It is therefore not possible to say whether the sponsor analyzed individual paired changes, used a model that included repeated measurements, or applied another approach. Those details should not be inferred from the stated endpoint alone.

Why does the non-randomized, sequential design matter?

In general, randomization helps balance measured and unmeasured characteristics between assigned groups. Here, the registry states that allocation was non-randomized, masking was absent, and there was no randomization to placebo. Participants could choose Phase 2 activities if eligible and interested. Thus, people entering a treatment pathway may differ from people who do not enter it, and participants who reach a later activity may differ from those who do not. These features limit the interpretation of comparisons between pathways and of changes over time.

Sequential does not mean that every participant received every intervention. The registry describes ketamine for some people and reports 24 participants with evaluable pre- and post-ketamine data. The record does not report the criteria for entering that group, the number who were eligible or interested, or reasons some participants did not proceed. Those details are not reported in the registry record.

How should dispersion and precision be considered?

The primary outcome is summarized using a mean and standard deviation. In general, standard deviation reflects variation among participant scores; it is not the standard error of the mean and is not a confidence interval. Greater variability can make it harder to estimate a group average precisely, especially when the available sample is limited. The registry provides no actual standard deviations or confidence intervals for MADRS in the posted results, so the amount of variability and precision cannot be assessed.

Over-dispersion is a general concern when the observed variation is greater than a statistical model expects. It can make model-based standard errors too small if the model's assumptions are not met. This general issue cannot be evaluated for ADEPT from the registry record because it does not report outcome distributions or the model used for analysis. It would be inappropriate to assume that over-dispersion was present or that a particular correction was applied.

What do the planning illustrations represent?

The sample-size section uses a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is described as a stated fraction of the observed effect. In general, such calculations show the sample size that would be needed under those assumptions to detect a specified effect. They are hypothetical planning quantities, not the number of participants actually analyzed, and not observed power. They should not be read as the trial's original design rationale.

The registry record does not report its own sample-size justification. It also does not report an interim-analysis plan, the primary test, any adjustment for covariates, or a procedure for handling multiple tests. Those omissions prevent a full reconstruction of the statistical analysis. The sample-size illustrations cannot answer whether the study was designed around a particular clinically meaningful MADRS difference.

For any recalculated quantities shown on the page, the intended interpretation is a simple, unadjusted calculation from posted summary statistics. A recalculation is not a replacement for the sponsor's analysis. If the posted sponsor result and a recalculated result disagree, the sponsor's own analysis takes precedence. In this record, the primary outcome summaries needed to interpret such a calculation are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and four analyses. It identifies MADRS as the primary outcome and lists the Snaith Hamilton Pleasure Scale (SHAPS) score as a secondary outcome. However, the registry record does not report how the analyses map to the outcomes, time points, or treatment pathways. The number of analyses alone does not establish how many statistical hypotheses were tested.

Multiplicity arises when several outcomes, time points, subgroups, or comparisons are examined. In general, conducting multiple tests can increase the chance of at least one apparently noteworthy result arising by chance. A prespecified strategy may control that risk, for example by defining a primary test or adjusting inference across a family of comparisons. The registry record does not report a multiplicity-adjustment strategy, a hierarchy of tests, or which analyses were designated confirmatory.

Missing-data information is limited. For TMS, 50 participants initiated treatment, 48 had evaluable pre- and post-treatment MADRS data and were analyzed, and two discontinued before assessment. For ketamine, 24 participants completed the activity with evaluable pre- and post-treatment MADRS data. The record does not report the number who began ketamine but lacked evaluable outcomes, reasons for missing measurements beyond the two TMS discontinuations, or any imputation or sensitivity analysis.

The described primary-outcome analysis population is restricted to Phase 2 participants, with no more than 50 participants. The registry record does not report an intention-to-treat analysis or explain whether anyone outside the evaluable paired-data groups was included in other analyses. These limits mean the reported analysis populations should not be treated as identical to the full enrollment of 123 participants. Without further details, the effect of missing outcomes or participant selection on the results 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.

Most frequent non-serious adverse event terms

The safety figures distinguish serious adverse events from other adverse events and give the number of participants at risk and affected in each listed group. For TMS and PAT, the record lists 50 participants at risk, zero with a serious adverse event, and 3 with another adverse event. For ketamine, it lists 24 at risk, zero with a serious adverse event, and 4 with another adverse event. For Phase 1, it lists 123 at risk, zero with a serious adverse event, and 23 with another adverse event. No deaths are listed in these groups.

These are group-level counts in the registry record. They are not a comparison of randomized treatment groups: the study was non-randomized, and the pathways differ in who participated and when. The counts also do not establish that events were caused by a particular activity. The record does not provide event descriptions for the other adverse events in the registry record, and no serious adverse-event terms are listed.

In general, zero reported serious events in a group does not prove that an event is impossible or that risks are absent. It means that no serious adverse events are recorded for that group in the posted figures. Counts should be interpreted with the group sizes and the study's non-randomized design in mind, without turning them into a causal comparison or a treatment recommendation.

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

This study matters as a registry record of a completed, sequential investigation into anhedonia and depression in young people. It documents a broad first phase of assessments and a second phase involving TMS, Positive Affect Training, and ketamine for some participants. The record also specifies a clinician-rated primary outcome and the time windows at which it was assessed.

What the record does not establish is the size or direction of any MADRS change. The posted registry record contains no primary-outcome means, standard deviations, changes, confidence intervals, or test results. Without these, readers cannot judge the magnitude of the observed data or the precision of an estimate. The absence of those values is not evidence that no change occurred; it means the result is not reported in the registry record.

The non-randomized, open-label design also matters. In general, a before-and-after change can be informative about the measured participants, but it cannot separate treatment effects from other explanations as a randomized comparison can. The sequential treatment pathways and participant choice further mean the groups cannot be assumed to be comparable. The record does not report adjustment methods that might address differences between participants.

The adverse-event figures provide counts in the listed groups, including zero recorded serious adverse events and no deaths. They should be read as descriptive reports, not proof of safety or a comparison of relative risk between treatments. The record does not identify serious-event terms, and the counts do not establish causation.

Finally, planning illustrations based on an observed effect are not observed power, and they do not show that the study was designed with a particular sample-size justification. The registry record does not report that justification. Overall, the record helps readers understand the study structure, measurement schedule, and analysis populations, while leaving important information needed to interpret efficacy estimates and statistical uncertainty unreported.

13. Why This Trial Matters Statistically

The study is statistically notable because it combines repeated outcome measurement with a sequential, non-randomized treatment structure. These design features make it important to distinguish within-person score changes from between-group treatment comparisons. A score measured before and after an activity can describe change over time, but it is not a substitute for a randomized control comparison.

The different analysis populations also deserve attention. The registry reports 48 evaluable TMS pairs after 50 participants initiated TMS, and 24 evaluable ketamine pairs among participants who subsequently completed ketamine. These counts identify who contributed to the listed paired assessments, rather than representing the entire enrolled cohort. The transition from the full enrollment to Phase 2 and then to the later ketamine assessment is part of the interpretation.

For biostatistical readers, this is a useful example of why a named primary endpoint and a defined assessment window do not, by themselves, give a complete account of the analysis. The registry record identifies MADRS as a mean score with standard deviation, but does not include its values or the methods used to estimate changes and uncertainty. It also lists multiple outcomes and analyses without reporting how multiplicity was handled.

The tables, plots, and planning illustrations can help organize quantitative information, but they cannot fill gaps in the registry record. Planning calculations describe hypothetical assumptions; they are not evidence of observed power, nor a statement of the original design justification. The case underscores the value of reporting outcome estimates, uncertainty, analysis populations, missing-data handling, and statistical methods clearly enough for readers to distinguish what the data show from what remains unknown.

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.

Several trial-specific limitations follow directly from the registry description. Allocation was non-randomized and masking was absent; the treatment pathways were open label and had no placebo randomization. The listed arms are therefore not a like-for-like control comparison. The record also says participants could choose Phase 2 activities if they qualified and were interested, so selection into treatment pathways may be relevant to interpretation.

The pathway was sequential, with some participants proceeding to ketamine after TMS and PAT. The 24 participants with evaluable ketamine assessments are a later group, not a separately randomized comparator. The registry record does not report eligibility details, the number who chose not to proceed, or reasons for not reaching the ketamine assessment. It also does not explain the two TMS discontinuations beyond noting that they occurred before assessment.

Most importantly for interpreting the primary outcome, the registry record does not report MADRS summary values, uncertainty estimates, or test results. It does not report the statistical test or model, covariate adjustment, missing-data methods, or a multiplicity strategy. The sample-size justification and any interim analyses are also not reported in the registry record.

The safety information is descriptive and does not establish causality. The record gives counts of affected participants but does not provide serious-event terms or further descriptions of other adverse events in the registry record. Taken together, these limits mean that the study structure and some participant counts can be described, but the magnitude, precision, and causal interpretation of the primary-outcome results cannot be established from the posted registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Anhedonia, Development, and Emotions: Phenotyping and Therapeutics — NCT05487885.
• Registry record last updated 2026-03-17; status last verified 2026-02.
• Results first posted 2026-03-17.
• 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.

18. Record Summary

The ADEPT Study is a completed Phase 4, non-randomized, unmasked, sequential study that enrolled 123 participants and addressed depression and anhedonia. The registry describes Phase 1 assessment activities and Phase 2 therapeutic activities, including TMS, Positive Affect Training, and ketamine for some participants. The treatment pathways were open label, with no randomization to placebo.

The primary outcome was mean MADRS score, measured before and after TMS over 2 weeks and before and after ketamine at 24 hours. Forty-eight participants had evaluable TMS measurements after 50 initiated TMS; 24 had evaluable measurements after completing ketamine. The registry also lists SHAPS as a secondary outcome.

The posted record lists no serious adverse events or deaths in the reported groups. It does not report the primary MADRS estimates, their precision, the statistical testing approach, or the study's sample-size justification. The record supports a description of the design and analysis populations, but not a quantitative interpretation of primary-outcome change.