The Effects of Antipsychotic Drugs on Brain Metabolism in Healthy Individuals: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effects of Antipsychotic Drugs on Brain Metabolism in Healthy Individuals (NCT02536846), a na phase 4 study. The primary outcome is Change in Brain Nicotinamide Adenine Dinucleotide Metabolites NAD+/NADH.

2. Clinical Question

The study’s stated aim is to investigate antipsychotic drug effects on healthy brain metabolism. Its primary outcome focuses on the ratio of nicotinamide adenine dinucleotide metabolites NAD+ and NADH. The registry describes a within-group comparison over time, rather than a comparison between olanzapine and a concurrent control treatment.

That distinction matters for interpretation. A before-and-after measurement can describe how values differed over the study period among those assessed. Without a separate comparator, a change cannot by itself distinguish an effect associated with olanzapine from other explanations, such as changes over time or measurement variability. This is a general limitation of interpreting single-group pre-post results, not a finding about what occurred in this study.

The registry record does not report the observed baseline or follow-up means, the mean change, its standard deviation, a confidence interval, or a statistical test for the primary outcome. It therefore does not establish the direction, magnitude, or precision of any observed change.

3. Trial Design

The registry identifies this as a Phase 4, single-group study in healthy individuals. Enrollment is listed as 35. Allocation is recorded as NA, and masking is recorded as none. The record does not describe a randomized treatment assignment or a separate control group, and it should not be interpreted as a like-for-like controlled comparison.

The intervention is olanzapine. The arm description states: “Olanzapine; a single 2.5 mg dose PO daily followed by 5 mg dose PO daily for 14 days.” The primary outcome timeframe is baseline and after 15 days medication period. The record does not give further details about how the medication schedule was implemented, the timing of assessments within the period, or adherence.

The primary objective is to investigate antipsychotic drug effects on healthy brain metabolism. The primary outcome is change in the brain NAD+/NADH metabolite ratio, measured by in vivo 31P magnetic resonance spectroscopy. Secondary outcomes include changes in brain-region volumes and surface areas, resting-state functional connectivity, GABA concentration, fractional anisotropy measured by diffusion tensor imaging, glutamate metabolite concentration, and the MATRICS Cognitive Consensus Battery total composite score. The registry lists 33 outcome measures overall.

Study start is recorded as 2017-11-17, primary completion as 2019-11-08, and status as completed. The record does not explain the basis for the enrollment target, describe interim analyses, or provide details of the statistical analysis plan. It also does not state which participants completed each assessment or entered each analysis. These omissions limit assessment of how closely the analyses followed the study plan and how representative the analyzed measurements may be.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Individuals between 21-50 years old without a psychiatric or serious medical diagnosis or family history or first degree relative with a psychotic disorder.

6. Primary Endpoint

The registry lists the primary outcome as Change in Brain Nicotinamide Adenine Dinucleotide Metabolites NAD+/NADH, measured over Baseline and after 15 days medication period.

The primary endpoint is change in the brain nicotinamide adenine dinucleotide NAD+/NADH metabolite ratio, measured by in vivo 31P magnetic resonance spectroscopy. The unit is a ratio, and the registry specifies a mean as the summary measure, with standard deviation as the dispersion measure. Measurements are scheduled at baseline and after 15 days medication period.

NAD+ and NADH are metabolites involved in cellular energy processes. In general, measuring their ratio in the brain can be used to characterize a metabolic feature of brain tissue. Magnetic resonance spectroscopy provides a way to estimate concentrations of selected metabolites in vivo, without requiring a tissue sample. These are general descriptions of the measurement and do not establish what the ratio represents clinically in this study or how it should be interpreted for an individual.

A change endpoint compares measurements from different time points. Reporting a mean change would describe the average direction and size of change among the participants included in that analysis; reporting its standard deviation would describe variation in individual changes. A confidence interval would help indicate the precision of the estimated average. The registry record does not report the observed mean values, mean change, standard deviation, confidence interval, or a test result for this endpoint. Thus the intended measurement is clear, but the actual result and its precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is described as a single-group design with measurements at baseline and after 15 days medication period. In general, a single-group pre-post analysis evaluates change within participants who have measurements at both time points. It differs from a parallel-group analysis, in which outcomes are compared between groups assigned to different interventions. Here, the registry describes no separate comparator, records allocation as NA, and records masking as none.

What does a mean change represent?

For a continuous outcome, a mean is the arithmetic average of observed values. A mean change is generally calculated by finding each participant’s change between time points and then averaging those changes among the participants included in the analysis. This is distinct from simply subtracting one group mean from another when the same participants contribute paired measurements, because paired data retain information about how each person’s measurements relate across time. The registry states that the primary outcome is summarized by a mean and standard deviation, but it does not explain the exact analysis or calculation used.

Standard deviation describes variability among measurements. For a change outcome, it can describe how much individual changes vary around the average change. A small standard deviation would indicate more clustered changes, while a large one would indicate more spread. These are general interpretations; the registry does not report a standard deviation for the primary endpoint.

How does a confidence interval help?

In general, a confidence interval gives a range of values compatible with the observed data and the method used to calculate the interval. Its width reflects precision: a narrower interval indicates greater precision under the model assumptions, while a wider interval indicates less precision. A confidence interval is not a guarantee that the true value lies inside the particular interval, and it does not resolve limitations arising from the design or measurement process. No confidence interval for the primary outcome is reported in the registry record.

A significance test, if reported, would address compatibility between the data and a specified null hypothesis under its assumptions. A p-value would not measure the size or clinical importance of a change, and it would not by itself establish that an intervention caused the change. The registry record does not report a primary-outcome p-value or describe the test used.

Why does the design matter?

Because the study is single-group, a change over time would not be contrasted with the change that might have occurred in a concurrent untreated or differently treated group. General sources of variation in pre-post measurements can include natural fluctuation, measurement error, changes in participant circumstances, and time-related effects. The record does not indicate whether any of these affected this study. The absence of a control comparison therefore limits causal interpretation, even if a within-group change estimate were available.

Repeated measurements may be correlated: values from the same individual can be more alike than values from different individuals. General analysis methods for paired data account for this dependence. Treating paired observations as independent can misrepresent uncertainty. The registry record does not state which model or test accounted for repeated measurements, nor whether all participants had measurements at both time points.

What is over-dispersion?

Over-dispersion is a general issue for outcomes whose variability is greater than assumed by a statistical model. For example, count data may vary more than a simple model expects because observations differ in underlying risk or because events cluster. A model that underestimates variability can produce confidence intervals that are too narrow and tests that appear more decisive than warranted. The primary endpoint is a continuous metabolite ratio, not a count outcome, and the record does not identify an over-dispersion concern or provide enough results to assess one. This concept is included as general statistical context, not as a claim about the analysis used.

The record’s sample-size assumptions describe a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is not the trial’s own design. Its stated approach is not a description of the actual single-group allocation, and it cannot be treated as observed power or as evidence that the study was adequately powered. No planning estimates are reported in the registry information.

For a planning calculation based on a prior observed effect, smaller fractions of that effect represent smaller target effects. In general, planning to detect a smaller effect requires more information under otherwise comparable assumptions. Such planning illustrations concern hypothetical future designs; they do not add evidence about the effect observed in this study. The registry record does not report the original sample-size justification or the statistical plan used for the completed study.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Olanzapine")
n   <- c(7)
m   <- c(-0.79)
sp  <- c(2.37)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Olanzapine  7  -0.790  2.370  -2.982  1.402

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 33 outcome measures, including the primary NAD+/NADH ratio and secondary measures concerning brain structure, functional connectivity, GABA, fractional anisotropy, glutamate metabolites, and cognitive performance. It also records 0 analyses. This means the registry record does not include analysis entries for these outcomes; it does not show estimates or test results that would allow readers to assess the reported findings.

When multiple outcomes or statistical tests are examined, the chance of at least one result appearing unusual can increase. General approaches to this issue include specifying a hierarchy of outcomes, adjusting inference for multiple comparisons, or treating secondary analyses as exploratory. The registry record does not report whether any such approach was planned or used. It also does not state whether the listed outcomes were all analyzed or how their results were selected for reporting.

Missing-data handling is not reported in the registry record. The record does not give the number of participants with measurements at each time point, the reasons for missing measurements, the analysis population, or the method used to handle incomplete observations. It therefore is not possible to assess whether the primary analysis used all enrolled participants, only those with paired measurements, or another defined group.

The record also does not report whether any participants were excluded from analyses or how protocol deviations were handled. These details matter because the interpretation of a mean change depends on who contributed data and on the assumptions used when observations are missing. No conclusions about missingness, exclusions, or the analysis population can be drawn from the registry record.

12. 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 registry’s Olanzapine safety summary records 0 serious adverse events among 10 at risk, 10 other adverse events among 10 at risk, and 0 deaths. These are the figures recorded for the safety summary; the registry does not provide descriptions of the other events or additional detail about their severity, timing, or relationship to treatment.

The “at risk” counts shown for the safety summaries are 10, while overall enrollment is listed as 35. The record does not explain why the safety denominator differs from enrollment or how the safety population was defined. The counts therefore should not be treated as a complete account of every enrolled participant’s experience.

Zero recorded serious events means none were entered in that serious-event summary for the listed at-risk group. It does not establish that no adverse experiences occurred, as the separate other-event count illustrates, and it does not rule out events that were not captured or entered. Likewise, the other-event count does not show the number of event types, their seriousness, or whether individuals experienced more than one event. The registry record does not give those details.

These data describe recorded safety counts and should not be used alone to make a comparative safety judgment. No concurrent control group is described, and the record does not provide a fuller account of adverse-event collection or follow-up.

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

The record establishes that the study was intended to examine antipsychotic drug effects on healthy brain metabolism, with change in brain NAD+/NADH ratio as the primary outcome. It describes a single-group olanzapine intervention and a baseline-to-follow-up measurement schedule. It also lists several secondary brain imaging, metabolite, and cognitive outcomes.

What the registry record does not establish is the size or direction of the primary outcome change. Numerical baseline and follow-up values, a mean change, variability, confidence interval, and statistical test are not reported. The record therefore does not allow readers to judge whether the average ratio changed, how variable individual changes were, or how precisely any change was estimated.

Nor does the design establish that any change was caused by olanzapine. General interpretation of pre-post studies requires caution because the absence of a concurrent comparator leaves changes over time without a control reference. The study record describes no randomized comparison, and its allocation is listed as NA. This is a limitation on causal attribution, not evidence for or against a particular biological effect.

The study concerns healthy individuals and a specific metabolite ratio measured over a limited medication period. Findings, if available, would not automatically answer questions about other populations, outcomes, or longer-term exposure. The registry record does not report the primary outcome findings or the analysis details needed to evaluate such extensions.

The safety summary records no serious adverse events or deaths in the listed counts, alongside other adverse events. Those counts are limited by the information recorded: the event descriptions and the reason the at-risk count differs from overall enrollment are not reported. They should not be interpreted as a comprehensive or comparative safety assessment.

14. Why This Trial Matters Statistically

This study is statistically notable because its primary question is framed around a within-person change in a continuous brain-metabolism measure. Such questions require clarity about the paired measurements, the population with complete data, and how uncertainty in individual changes is summarized. The registry identifies a mean and standard deviation as the intended summary measures, but does not report the resulting estimates.

The single-group design also makes the distinction between description and causal inference especially important. A mean change can describe what was observed over time among analyzed participants. Without a concurrent comparator, it cannot on its own separate an intervention-associated change from other time-related or measurement-related influences. This general point applies regardless of whether a change is statistically distinguishable from zero.

The broad set of secondary outcomes adds another statistical consideration. The record lists 33 outcome measures across metabolic, structural, functional, and cognitive domains. For studies with multiple outcomes, a prespecified strategy for prioritizing and interpreting results helps readers distinguish confirmatory analyses from exploratory ones. That strategy is not reported in the registry record.

Finally, an outcome description is not a result. The registry gives a defined primary endpoint and timeframe, but does not include the numerical results or analysis entries needed to evaluate effect size and precision. Keeping design information separate from outcome evidence prevents the study’s rationale and measurement plan from being mistaken for evidence of a particular result.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to this record constrain interpretation. The design is listed as single-group, allocation as NA, and masking as none; no concurrent comparator is described. Thus a before-and-after difference, if reported elsewhere, would not by itself isolate the effect of olanzapine from other changes over time.

The registry does not report the primary endpoint results. It gives no observed mean at either time point, mean change, standard deviation, confidence interval, or test result. Without these, neither the estimated change nor its precision can be evaluated from the registry record.

Although enrollment is listed as 35, the number contributing primary-outcome data is not reported. The record does not describe missing measurements, participant exclusions, adherence, protocol deviations, or the analysis population. These omissions make it difficult to determine the amount of information supporting any analysis or the potential effect of incomplete follow-up.

The record lists 33 outcome measures but does not describe multiplicity handling, outcome hierarchy, or which analyses were conducted. It records 0 analyses, leaving no analysis entries with which to assess the methods or results. The rationale for enrollment and the study’s statistical analysis plan are also not reported.

Safety information is limited to summary counts. The record does not describe the other adverse events or explain why the listed at-risk count differs from overall enrollment. The timing, completeness, and methods of adverse-event collection are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The Effects of Antipsychotic Drugs on Brain Metabolism in Healthy Individuals — NCT02536846.
• Registry record last updated 2022-10-03; status last verified 2022-09.
• Results first posted 2021-08-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes NCT02536846, “The Effects of Antipsychotic Drugs on Brain Metabolism in Healthy Individuals,” as a completed Phase 4, single-group study with enrollment of 35. The intervention is olanzapine, and the primary outcome is change in the brain NAD+/NADH metabolite ratio measured by in vivo 31P magnetic resonance spectroscopy at baseline and after 15 days medication period.

Allocation is recorded as NA and masking as none. The record lists multiple secondary outcomes and 33 outcome measures overall, but records 0 analyses. It does not report numerical primary-outcome results, analysis details, missing-data methods, or multiplicity handling. The safety summary lists 0 serious adverse events among 10 at risk, 10 other adverse events among 10 at risk, and 0 deaths; further event details are not reported in the registry record.