Vortioxetine (Lu AA21004) 10 and 20 mg for Treatment of Major Depressive Disorder With Sexual Dysfunction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vortioxetine (Lu AA21004) 10 and 20 mg for Treatment of Major Depressive Disorder With Sexual Dysfunction (NCT01364649), a randomized phase 3 study. The primary outcome is Change From Baseline in the Changes in Sexual Functioning Questionnaire Short-Form (CSFQ-14) Total Score at Week 8.

2. Clinical Question

The registry record describes a randomized, double-blind, parallel-group, active-controlled study. Its official title identifies sexual functioning as the focus, and the primary endpoint is the change in the CSFQ-14 total score at Week 8. The posted analysis estimates a larger adjusted mean change for vortioxetine than for escitalopram. That result describes the outcome as measured in this trial; it does not by itself establish how the result applies to people outside the enrolled population or to other treatment settings.

Placebo appears in the listed interventions and as a matching capsule in the vortioxetine arm description, but the posted primary comparison is between vortioxetine and escitalopram. The registry record does not describe a placebo comparison for this primary result. The central statistical question is therefore the size and precision of the between-arm difference in CSFQ-14 change, rather than whether either arm changed from baseline in isolation.

3. Trial Design

This was a Phase 3 randomized, quadruple-masked, parallel-group study with an active comparator. The registry record lists an enrollment of 447 and a completed status. The recorded start is 2011-06, and primary completion is recorded as 2013-12. Takeda is listed as the sponsor.

The two arms represented in the posted primary outcome are vortioxetine and escitalopram. Both were administered once daily, beginning at 10 mg for 1 week, with dose adjustment up to a maximum 20 mg for up to 7 weeks. The arm descriptions then specify capsules during Week 8: placebo-matching capsules for vortioxetine and escitalopram 10 mg capsules for the escitalopram arm. The registry record does not describe the detailed dose-adjustment rules or explain the purpose of the Week 8 capsule arrangements beyond their listed contents.

The primary endpoint was assessed at baseline and Week 8. The primary analysis used a mixed model for repeated measurements, with treatment, center, week, and treatment-by-week interaction as fixed effects. Baseline CSFQ-14 total score-by-week was included as a covariate, and the model used a completely unstructured covariance matrix. The analysis population was defined as randomized participants who received at least 1 dose of study drug and had outcome data available.

The posted endpoint results include 165 participants in the vortioxetine arm and 173 in the escitalopram arm. The registry record does not explain how these endpoint counts relate to the overall enrollment or report the reasons participants lacked outcome data. Although a placebo intervention is listed, the posted primary results report the active-arm comparison; a separate placebo arm result is not reported in the registry record.

Further details about how randomization was generated, how masking was implemented, the original sample-size justification, or any interim analyses are not reported in the registry record. Those omissions limit what can be inferred about design decisions beyond the characteristics explicitly recorded.

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: Participants with a diagnosis of major depressive disorder were enrolled equally in 1 of 2 (flexible doses of either vortioxetine (Lu AA21004) 10/20 mg once daily (QD) or escitalopram 10/20 mg QD) treatment groups.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants from the Full Analysis Set (FAS), defined as all participants who were randomized and received at least 1 dose of study drug, who had data available for this outcome measure.

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 randomized set (N=447): All study participants who were screened and randomized to one of two treatment arms.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in the Changes in Sexual Functioning Questionnaire Short-Form (CSFQ-14) Total Score at Week 8, measured over Baseline, Week 8.

The primary endpoint was change from baseline in the Changes in Sexual Functioning Questionnaire Short-Form total score at Week 8. The CSFQ-14 is a structured self-reported questionnaire intended to measure illness- and medication-related changes in sexual functioning. It has 14 items, rated on a 5 point scale from 1 to 5, and a total score range from 14 to 70. Higher scores indicate higher sexual functioning, and a positive change from baseline indicates improvement in the score.

The total score combines questions across areas including pleasure, desire and frequency, desire and interest, arousal, and orgasm. Using a total score gives a single outcome for the primary comparison while retaining a measure that covers multiple aspects of sexual functioning. The registry record does not report a threshold for a clinically important change, so the numerical size of a score difference should not be interpreted as crossing a particular clinical boundary.

The endpoint is a change score, not simply the Week 8 score. The reported primary model adjusted for baseline score and repeated observations over time, then estimated the between-arm difference at the relevant assessment. Because the questionnaire is self-reported, the outcome represents participants' reported functioning. The registry record does not provide details about questionnaire completion procedures or the handling of individual unanswered items.

7. Results Posted in the Registry

• Escitalopram: mean 6.60 versus 8.80 on control; difference -2.20 (95% CI -3.97 to -0.43), standardized effect d = -0.26; z-test p = 0.015.

8. Statistical Interpretation

9. Statistical Methods Explained

What does the repeated-measures model estimate?

The primary analysis was a mixed model for repeated measurements, or MMRM, described as an analysis of covariance. In general, repeated-measures models analyze a series of measurements from participants while accounting for the relationship among measurements from the same person. This can use information across assessment times rather than treating each time point as an unrelated outcome. The reported endpoint is the Week 8 change in CSFQ-14 total score.

The registry record specifies treatment, center, week, and treatment-by-week interaction as fixed effects. In general, fixed effects represent modeled group or design factors whose contributions are estimated directly. The treatment-by-week interaction allows the treatment contrast to vary across assessment weeks rather than forcing one common difference at every week. Baseline CSFQ-14 total score-by-week was included as a covariate, so the analysis accounts for baseline score in estimating the changes over time. The registry record does not give further detail about how centers were represented or whether any other terms were included.

The model used a completely unstructured covariance matrix. In general, a covariance matrix describes how measurements at different times relate to one another. An unstructured form does not impose a simple pattern on those relationships; it allows the model to estimate each variance and covariance rather than requiring a prespecified regular pattern. This flexibility can be useful when the time profile is not assumed to follow a particular covariance structure, although it requires estimating more covariance parameters than a more restrictive structure. The record does not report an alternative covariance analysis or sensitivity results.

What is a least-squares mean?

A least-squares mean is a model-based estimated mean, adjusted for the factors and covariates included in the model. It is not necessarily the same as a raw arithmetic average of the observed values. The reported between-arm estimate of 2.2 points is the sponsor's least-squares mean difference, with vortioxetine minus escitalopram as the direction indicated by the arm results. The model-based estimate is the principal result to interpret because it comes from the analysis specified for the primary outcome.

The arm-level values of 8.8 and 6.6 are posted mean changes, and the associated standard errors are 0.64 for each. The standard error describes the estimated sampling variability of a mean estimate: smaller standard errors generally indicate more precise estimates, conditional on the analysis and data. An arm-level standard error is not the same quantity as the standard deviation of individual participants' scores. The registry record does not provide individual-level distributions for this endpoint.

How should the recalculation be understood?

The simple recalculation uses posted summary statistics to estimate an unadjusted comparison, rather than reproducing the adjusted repeated-measures model. The recalculated difference is -2.2 for escitalopram minus vortioxetine, with an interval from -3.974 to -0.426 and p = 0.015. Reversing the order of the arms changes the sign but not the underlying contrast. The recalculation also estimates a pooled standard deviation of 8.322 and a standardized difference of -0.264. The pooled standard deviation is approximate, as indicated for that calculation, and the standardized difference is based on that approximation.

Because the recalculation is unadjusted and based on summary data, it is a check on the scale and direction of the posted comparison, not a replacement for the sponsor's prespecified model-based analysis. The recalculated interval and p-value are close to, but not identical with, the sponsor's reported values. The registry record does not flag a discrepancy. No inference should be made that the recalculation reproduces the full model, because the individual participant data and complete model output are not reported in the registry record.

What does the p-value address?

In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the analysis assumptions were true. The sponsor reported p = 0.013 for the primary contrast, while the simple unadjusted recalculation reports p = 0.015. These are analysis-specific results, and the model-based value belongs to the primary analysis. A p-value does not measure the size or clinical importance of the effect. It also does not state the chance that the finding will replicate.

In general, a confidence interval combines an estimate with its uncertainty under a statistical model. For the primary result, the interval is 0.48 to 4.02 points for the vortioxetine-minus-escitalopram contrast. The interval is on the same score-point scale as the estimated contrast. Its width reflects uncertainty; its endpoints are not a guarantee that the true effect lies within that particular interval. The confidence level describes the long-run behavior of the interval procedure under its assumptions, rather than certainty about a single interval.

Which participants contributed to the primary analysis?

The Full Analysis Set was defined as participants who were randomized, received at least 1 dose of study drug, and had data available for the outcome measure. This definition makes clear that randomization alone was not sufficient for inclusion in this endpoint analysis. The posted outcome counts are 165 for vortioxetine and 173 for escitalopram. The registry record does not describe the extent or reasons for missing observations, whether all available repeated measurements were used for every participant, or what assumptions about missingness were applied.

In general, an MMRM can use observed repeated measurements without filling in a single value for every missing visit, but the validity of the resulting estimates depends on assumptions about the missing-data process and the model. The registry record does not report the assumptions, diagnostic checks, or sensitivity analyses needed to assess this aspect in detail. It is therefore appropriate to describe the analysis method as posted without asserting that missingness could not bias the comparison.

10. Confidence Intervals and Precision

The sponsor-reported estimate is a 2.2-point difference in adjusted mean change, with a 95% confidence interval from 0.48 to 4.02 points, expressed as vortioxetine minus escitalopram. This interval communicates uncertainty around the model-based estimate. Values closer to the lower limit represent a smaller difference, while values closer to the upper limit represent a larger difference, under the analysis model. The registry record does not report a threshold for deciding whether any particular point difference is clinically important.

The reported interval does not include zero. In the context of the model and stated comparison, the interval therefore indicates that the estimated difference is on the positive side throughout the interval. This describes statistical compatibility under the model, not certainty about the result or proof that a difference matters to participants. The reported p-value, p = 0.013, is consistent with the same model-based comparison, but it should not be treated as a measure of effect size.

The simple recalculation reports a 95% interval from -3.974 to -0.426 because its contrast is expressed as escitalopram minus vortioxetine. The sign is opposite to the sponsor's contrast, so the two intervals describe the same direction when their subtraction order is taken into account. The recalculation is unadjusted and should not be confused with the primary model-based interval.

Precision also depends on the population and data contributing to the estimate. The primary analysis population included participants with available outcome data, with posted counts of 165 and 173 in the two arms. The registry record does not explain the number or pattern of missing endpoint observations, report a separate confidence interval for each arm mean, or provide sensitivity analyses. Those omissions limit assessment of how robust the stated precision is to missing data or alternative modeling choices.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations based on the observed effect, not the trial's original sample-size justification. The assumptions for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row uses the stated fraction of the observed effect as the effect to detect.

The 80% power column gives the estimated number of participants per arm for a design with an 80% chance of detecting the specified effect under the planning assumptions, if that effect and the assumptions were true. The 90% power column gives the corresponding per-arm planning count for a 90% chance. These are design calculations, not statements about the probability that the completed trial found a true effect.

For planning for 100% of the observed effect, the illustrations are 225 participants per arm for 80% power and 301 participants per arm for 90% power. For planning for 75% of the observed effect, they are 400 participants per arm for 80% power and 535 participants per arm for 90% power. For planning for 50% of the observed effect, they are 899 participants per arm for 80% power and 1,203 participants per arm for 90% power. Smaller effects require more participants to detect under the same assumptions, which is why the planning counts increase as the assumed effect becomes smaller.

These figures are not observed power. They do not describe the probability that this completed trial detected an effect, and they are not evidence about the study's original design target. The original sample-size rationale and any other design assumptions are not reported in the registry record. The planning display should be read as an illustration of how sample size changes when the target effect and desired power change, rather than as a reconstruction of the trial's design.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -2.200; pooled standard deviation σ = 8.322.
2. n = 2 × (1.96 + 0.842)² × 8.322² / -2.200² = 224.6, rounded up to 225 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -2.2                      # observed difference in means
sigma <- 8.32234399215807                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1364649)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 225 (80% power), 301 (90% power)
 75% of observed effect: n per arm = 400 (80% power), 535 (90% power)
 50% of observed effect: n per arm = 899 (80% power), 1,203 (90% power)
power.t.test: 225.6 
Simulated power at n = 225 per arm: 0.799 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Analyses Reported by the Sponsor

The sponsor's reported primary analysis is the mixed model for repeated measurements. It estimates a least-squares mean difference of 2.2 points, with a 95% confidence interval from 0.48 to 4.02 and p = 0.013. This is the adjusted analysis described for the endpoint and is the result to use when describing the primary comparison.

The simple recalculation uses posted summary statistics and is unadjusted. It expresses the contrast in the reverse direction, as escitalopram minus vortioxetine, yielding -2.2 with a 95% interval from -3.974 to -0.426 and p = 0.015. A reversed contrast changes the sign, not the comparison's direction in substantive terms. The two analyses are similar in broad direction, but their estimates and uncertainty measures are not identical because they are not the same calculation.

The registry record does not flag a discrepancy between the sponsor's analysis and the recalculation. The recalculation is best treated as a transparent summary-statistic check, not a substitute for the sponsor's adjusted model. It cannot reproduce the full repeated-measures analysis from the posted aggregate values alone.

14. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary analysis for change in CSFQ-14 total score at Week 8. It also lists two secondary outcomes: change from baseline in CSFQ-14 total score at other assessed time points, and the number of participants shifting from abnormal to normal CSFQ-14 status at each assessed week. There are 3 outcome measures and 1 posted analysis in the record described for this result.

When a study evaluates multiple outcomes or time points, the chance of obtaining at least one apparently unusual result can increase if many separate tests are considered. Statistical approaches to multiplicity can address this in different ways, but the registry record does not report whether any adjustment was planned or applied. It also does not report a testing hierarchy, how secondary outcomes relate to the primary endpoint, or the results for the listed secondary outcomes. The primary p-value should therefore be understood as reported for the primary comparison, without assuming a particular family-wise multiplicity strategy.

The primary analysis population was the Full Analysis Set, defined as randomized participants who received at least 1 dose of study drug and had data available for the outcome. The posted endpoint counts are 165 in the vortioxetine arm and 173 in the escitalopram arm. The registry record does not report how many participants were randomized to each arm, the reasons outcome data were unavailable, or whether the primary analysis used a particular missing-data sensitivity procedure.

In general, repeated-measures models can use observed values across visits, but estimates rely on assumptions about how missing observations relate to observed and unobserved outcomes. The registry record does not state those assumptions, describe missing-data diagnostics, or report sensitivity analyses. It would be unwarranted to assume that missingness was absent or that any particular missing-data mechanism was established.

The analysis description gives model terms and the covariance structure, but other aspects of the statistical plan are not reported in the registry record. Details about an original sample-size justification, interim analyses, multiplicity control, and alternative analyses are not reported. The record also does not explain whether the analysis population definition or analysis methods changed during the study.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: depression (0.9%), mesenteric vein thrombosis (0.5%), angina pectoris (0.4%), anxiety (0.4%), nephrolithiasis (0.4%).

The registry record reports serious adverse events for 3 of 224 participants at risk in the vortioxetine group and 1 of 221 participants at risk in the escitalopram group. It also reports other adverse events affecting 90 of 224 participants at risk in the vortioxetine group and 60 of 221 at risk in the escitalopram group. These are event-category counts as posted; the registry record does not provide definitions for the separate categories in this summary.

Listed serious adverse event terms and percentages include Depression, 0.9%; Mesenteric vein thrombosis, 0.5%; Angina pectoris, 0.4%; Anxiety, 0.4%; and Nephrolithiasis, 0.4%. The registry record does not specify group attribution for these listed terms in the information, so they should not be assigned to a particular arm. Death counts are not reported in the registry record.

These figures are descriptive safety counts. They do not by themselves establish that an event was caused by a study drug, and the registry record does not provide the clinical details needed to assess individual events. The at-risk counts differ from the posted endpoint analysis counts; the record does not explain that difference. Safety counts should therefore be read separately from the CSFQ-14 efficacy analysis population and estimate.

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

The primary result indicates that the model-estimated change in CSFQ-14 total score at Week 8 was higher for vortioxetine than for escitalopram in the analyzed population. The reported adjusted difference was 2.2 points, with a 95% confidence interval from 0.48 to 4.02 and p = 0.013. The endpoint's scoring description gives the direction: a positive change from baseline corresponds to a higher sexual functioning score.

This statistical result does not determine whether a 2.2-point difference is important to participants. The registry record does not state a minimally important difference, responder threshold for the primary endpoint, or interpretation standard for changes in the total score. Statistical evidence about a difference and evidence about its practical meaning are related but distinct questions.

The comparison is between two active treatment arms in a study of adults with well-treated major depressive disorder experiencing SSRI-induced sexual dysfunction. The result does not establish a comparison with placebo, despite placebo appearing in the intervention listing and arm description. It also does not answer whether the observed pattern persists beyond Week 8, because the posted primary result is for that assessment and the registry record does not provide longer-term results in this analysis.

The estimate applies to the participants included in the Full Analysis Set for this endpoint: those randomized, treated with at least 1 dose, and with outcome data available. It should not automatically be generalized to other populations or contexts. The registry record does not provide enough information to judge how participants with missing outcome data might have differed from those analyzed.

Finally, the p-value and confidence interval do not establish a mechanism, explain why participants' scores changed, or predict an individual's response. They quantify the group comparison under the stated analysis. The listed secondary outcomes may address additional aspects of CSFQ-14 change, but their results are not reported in the primary result under discussion.

17. Why This Trial Matters Statistically

This trial illustrates why a continuous patient-reported outcome needs to be interpreted on both its scale and its model. The CSFQ-14 has a defined score range and a stated direction, so the estimated difference can be expressed in score points. At the same time, the registry record does not identify a threshold that would turn a score-point difference into a judgment about clinical importance. Statistical precision and clinical meaning should not be conflated.

It also illustrates the distinction between an adjusted primary analysis and a summary-statistic recalculation. The sponsor's repeated-measures model includes specified treatment, center, time, interaction, and baseline terms. A simple recalculation from arm summaries is easier to inspect but does not account for those same features. Reporting both perspectives can clarify the direction and rough scale of the comparison, while preserving the model-based analysis as the primary result.

Repeated assessments raise analytic questions about correlations across time, covariance structure, and missing observations. The registry record describes the model and its unstructured covariance but does not report missing-data assumptions or sensitivity analyses. This makes the description of the statistical method informative while leaving important details about robustness unresolved.

The planning illustrations also show how a smaller target effect requires more participants under otherwise fixed assumptions. Those calculations are useful for understanding design tradeoffs, but they are not evidence about the trial's original planning or about the power of the completed study. Separating planning calculations from observed results prevents a common misinterpretation of power analyses.

Overall, the record supports a careful reading of an adjusted Week 8 comparison, with explicit limits on interpretation. It also shows why confidence intervals, population definitions, multiplicity information, and missing-data reporting matter alongside a p-value.

18. 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 primary endpoint is a self-reported questionnaire score. That makes participants' reports central to the outcome, but the registry record does not describe questionnaire administration, item-level missingness, or procedures for handling incomplete questionnaires. It also does not report a threshold for a clinically important change in CSFQ-14 total score. The numerical difference can be described in scale points, but its practical importance cannot be established from the posted information alone.

The primary result is limited to Week 8, and the trial used flexible dosing up to a maximum 20 mg in each arm after the initial 10 mg period. The registry record does not provide dose-specific endpoint estimates or describe the detailed dose-adjustment rules. The pooled arm comparison therefore does not reveal how results might differ by dose or dose adjustment.

The analysis used a Full Analysis Set that required participants to have outcome data available. The registry record does not explain why the endpoint counts were 165 for vortioxetine and 173 for escitalopram, relative to overall enrollment of 447, or describe the pattern of missing outcomes. No missing-data sensitivity analysis is reported in the information available for this result. This limits assessment of how missing data could affect the estimate.

The primary outcome is one of several outcomes listed, but multiplicity procedures and results for the listed secondary outcomes are not reported in the registry record. The original sample-size justification, interim analyses, detailed randomization procedures, masking implementation, and a full statistical analysis plan are also not reported. These gaps restrict evaluation of design choices and robustness beyond the stated primary model.

Finally, the posted primary comparison is between two active treatment arms in the population described by the trial title and endpoint definition. The registry record does not report a primary placebo comparison, and the result should not be extended to populations or treatment settings not represented by the study description.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Vortioxetine (Lu AA21004) 10 and 20 mg for Treatment of Major Depressive Disorder With Sexual Dysfunction — NCT01364649.
• Registry record last updated 2014-10-09; status last verified 2014-10.
• Results first posted 2014-10-09.
• 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.

22. Record Summary

This completed Phase 3 randomized, quadruple-masked, parallel-group, active-controlled study evaluated vortioxetine compared with escitalopram for sexual functioning in adults with well-treated major depressive disorder experiencing SSRI-induced sexual dysfunction. Takeda is listed as sponsor. The registry record lists enrollment of 447, a start of 2011-06, and primary completion in 2013-12.

The primary endpoint was change from baseline in CSFQ-14 total score at Week 8. The sponsor-reported MMRM analysis estimated a vortioxetine-minus-escitalopram difference of 2.2 points, with a 95% confidence interval from 0.48 to 4.02 and p = 0.013. The analysis population consisted of randomized participants who received at least 1 dose and had outcome data available.

The record also lists secondary CSFQ-14 outcomes, but their results, multiplicity procedures, missing-data sensitivity analyses, and the original sample-size rationale are not reported in the registry record. The primary result should be understood as a model-based group comparison at Week 8, with the stated population and reporting limitations.