DECIFER: Depression and Citalopram In First Episode Recovery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for DECIFER: Depression and Citalopram In First Episode Recovery (NCT01041274), a randomized phase 4 study. The primary outcome is Calgary Depression Scale for Schizophrenia (CDSS).

2. Clinical Question

The central statistical question is about the difference in depression-scale outcomes between randomized groups over follow-up. The CDSS was scheduled for assessment from screening and baseline through week 52, with multiple visits in between. A longitudinal comparison could consider the pattern of scores over time, but the registry record does not identify a particular summary time point, change score, or longitudinal model as the primary analysis. It also does not report an estimate of the between-group difference or its uncertainty. Accordingly, the clinical question can be described from the trial's stated aims, but the posted results do not establish how the groups compared on the primary measure.

3. Trial Design

DECIFER is a phase 4, randomized, parallel-group trial recorded as completed. The registry lists 95 participants and the conditions schizophrenia and schizophreniform disorder. The study start is recorded as 2010-01 and primary completion as 2014-12. Those dates describe the registry record and do not, by themselves, supply information about recruitment pace or follow-up completion.

The two arm descriptions specify daily citalopram, flexibly dosed according to clinician judgment, or daily placebo, each for 12 months. The study summary frames citalopram as an add-on to an established second-generation antipsychotic regimen and standardized psychoeducation. The record lists psychoeducation, cognitive behavioral therapy, and functional magnetic resonance imaging among the interventions, but it does not explain their roles in the treatment arms or identify which participants received them. It also does not provide further details of antipsychotic choice or treatment changes.

Randomization and a parallel model are recorded. The masking designation is quadruple, but the record does not specify which participant, clinician, assessor, or other roles were masked, nor how masking was maintained. Details such as the randomization sequence, allocation concealment, and site structure are not reported in the registry record.

The CDSS is the primary outcome measure, described as a mean with standard deviation. Assessments were scheduled at screening, baseline, weeks 1-8, and weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52. The registry also names the SANS, BPRS, ISST, and Heinrich Quality of Life Scale as secondary outcomes. The registry's stated trial hypothesis also mentions relapse, but the information does not give a relapse definition or result. No detailed statistical analysis plan, sample-size justification, or analysis population definition is reported.

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

Analysis population for the primary outcome, as defined in the registry: Not all participants completed the CDRS assessment at each time point. Results are reported for all participants who completed the CDRS assessment.

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 Calgary Depression Scale for Schizophrenia (CDSS), measured over Screening, Baseline, Weeks 1-8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52.

The primary endpoint is the Calgary Depression Scale for Schizophrenia (CDSS), a rater-administered measure of depressive symptoms in schizophrenia. It consists of 9 questions, each scored from 0 to 3, and the total score ranges from 0 to 27. A higher score indicates more depressive symptoms. The scale is used to quantify symptom severity in a population in which the study summary says depressive symptoms are common.

The registry identifies the endpoint as a continuous measure summarized by a mean and standard deviation. In general, a mean describes the central level of a set of scores, while a standard deviation describes how spread out individual scores are around that mean. Neither statistic alone describes the uncertainty in a comparison between randomized groups.

Repeated assessments were scheduled from screening and baseline through week 52. Repeated measurement can describe whether scores change over time and whether the pattern differs by assigned group. That interpretation depends on a defined analysis, including how visits are combined or modeled and how incomplete follow-up is handled. Those details are not reported in the registry record. The registry also states that results include participants who completed the CDRS assessment at each time point; the outcome title uses CDSS, and the record does not clarify this naming inconsistency.

The endpoint is relevant to the stated depression question, but no single time-point contrast, group mean, estimated treatment difference, confidence interval, or test result is reported in the record for this measure. The scheduled assessments and scale description therefore define what was intended to be measured, not the magnitude or precision of a treatment-group comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical description is limited: the registry identifies a randomized, parallel-group design, a continuous primary outcome summarized as a mean with standard deviation, and a schedule of repeated CDSS assessments. It does not report the analysis model, a primary comparison time point, a treatment-effect estimate, or a confidence interval. The concepts below are general explanations of how such information is usually interpreted, not claims about analyses used in this trial.

What does a mean and standard deviation describe?

For a continuous measure, the mean is the arithmetic average of the observed scores in a defined group and at a defined time. The standard deviation describes the dispersion of individual scores around that average. In a symptom scale, the mean gives a group-level summary, while the spread indicates how much participants' scores vary. A mean and standard deviation do not show the full distribution and do not, on their own, answer whether randomized groups differ.

A comparison requires a clearly stated contrast. For example, an analysis might compare group means at a particular visit or compare change from baseline. The treatment contrast is an estimate of the difference defined by that analysis. Interpretation depends on its direction, magnitude, and uncertainty. No such CDSS contrast is reported in the registry record, so there is no numerical treatment effect to interpret.

Why does uncertainty matter?

In general, a confidence interval is a range of values compatible with the data and the assumptions of the analysis at a stated confidence level. A narrow interval indicates greater precision than a wide interval, while an interval spanning values that would imply meaningfully different conclusions leaves more uncertainty. The registry record does not report a confidence interval for the primary outcome. It also does not report a p-value for a primary comparison. A p-value, in general, measures how unusual data at least as incompatible with a specified null hypothesis would be under that hypothesis and the model assumptions; it does not measure the probability that a treatment works or the size of an effect.

How can repeated measurements be analyzed?

The CDSS schedule includes screening, baseline, weeks 1-8, and later visits through week 52. Multiple observations from one participant are related rather than independent. A longitudinal analysis can account for that within-participant correlation and estimate an overall pattern or a group-by-time contrast. Other possible approaches include analysis at a prespecified visit or an analysis of change from baseline. These are general options, not methods identified for DECIFER. The registry record does not specify which visits entered the primary analysis, how time was represented, or how correlation among repeated scores was handled.

Repeated data also make the handling of incomplete visits important. A participant may contribute a score at some visits but not others. The registry states that not all participants completed the CDRS assessment at each time point and describes results as including participants who completed the assessment at each time point. It does not give the number assessed at each visit, reasons for missing measurements, or a method for handling missing values. The CDSS/CDRS naming variation in that description is not explained.

What does randomization contribute?

In general, random assignment aims to make treatment groups comparable at the start with respect to both measured and unmeasured characteristics. It supports a causal interpretation of a between-group contrast when the analysis preserves the randomized comparison and other assumptions are reasonable. The registry labels the study randomized, but does not report sequence generation, concealment, adherence, treatment switching, or the analysis population. Those details are needed to assess how closely a particular analysis reflects the randomized assignment.

The record also labels masking as quadruple. Masking can reduce the influence of expectations on care, outcome assessment, or reporting, depending on who is masked and how procedures are implemented. The identity of the masked roles and the methods used to maintain masking are not reported. The label alone does not establish that masking was successful.

What do the planning illustrations mean?

In general, sample-size planning asks how many participants would be needed for a specified statistical design to detect an effect of a chosen size with a chosen probability, under stated assumptions. A planning illustration based on an observed effect is not a prospective justification for the trial's enrollment target. Nor is it observed power, which is not a useful substitute for reporting the treatment-effect estimate and its uncertainty. The registry record does not report the trial's own sample-size rationale or its assumed effect size. Its description of planning illustrations specifies a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of the observed effect; those are illustration assumptions, not evidence of the original design rationale.

The record does not report interim analyses, multiplicity procedures, a prespecified statistical analysis plan, or results for the primary endpoint. These omissions prevent a fuller assessment of how the repeated outcome schedule and multiple outcomes were incorporated into formal inference.

10. Multiplicity, Missing Data and Analysis Populations

The CDSS was assessed repeatedly from screening and baseline through week 52, and the registry names several secondary outcomes: SANS, BPRS, ISST, and the Heinrich Quality of Life Scale. Repeated visits and multiple outcomes create multiple opportunities to examine data. In general, when many comparisons are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the multiplicity or interpretation is appropriately cautious. The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or a prespecified primary time point. It is therefore not possible to determine how any multiplicity was handled.

Missing outcome data are also relevant. The registry states that not all participants completed the CDRS assessment at every time point and says results are reported for participants who completed the assessment at each time point. It does not report the number of missing assessments by group or visit, reasons for missingness, or the statistical approach used to address it. Complete observations can differ from incomplete observations, so the analyzed subset may not represent all randomized participants. The CDSS outcome title and CDRS wording in the missing-assessment description are inconsistent; the record does not explain whether this is a typographical issue or a different measure reference.

The analysis population is not defined in the registry record. It is not stated whether the primary analysis followed all randomized participants according to assigned group, included only participants with available outcome data, or used another population. The record also does not report sensitivity analyses for missing data. These omissions limit evaluation of the robustness and generalizability of any potential result. Since no primary endpoint analysis is reported, the effect of these choices on an estimated treatment contrast cannot be assessed.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: psychiatric hospitalization (8.7%), incarceration (2.2%), medical hospitalization (2.0%), drug-related hospitalization (2.0%).

The registry reports serious adverse events by arm. In the citalopram group, 5 participants were affected, with 49 participants at risk. In the placebo group, 4 participants were affected, with 46 participants at risk. For other adverse events, the corresponding affected counts are 22 of 49 in the citalopram group and 18 of 46 in the placebo group. These are counts of participants reported as affected, not event rates calculated. No additional calculation is needed to describe them.

These figures are descriptive and do not establish that an event was caused by the assigned treatment. The record does not provide an adjusted or unadjusted statistical comparison, confidence intervals, or a detailed definition of how events were collected in the information available for this analysis. The registry also lists serious-event terms and percentages: Psychiatric Hospitalization, 8.7%; Incarceration, 2.2%; Medical Hospitalization, 2.0%; and Drug-related hospitalization, 2.0%. The denominator and treatment-arm attribution for those percentages are not reported in the listed terms, so they should not be interpreted as arm-specific comparisons.

Deaths are not reported in the registry record. The event counts alone do not show whether differences are compatible with random variation or whether participants differed in exposure time or follow-up completeness. They should be read as reported safety summaries, not as evidence of comparative risk.

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

The record establishes that DECIFER was a randomized, parallel, quadruple-masked, phase 4 trial comparing daily citalopram with daily placebo for 12 months in first-episode schizophrenia or schizophreniform disorder. It identifies the CDSS as the primary continuous outcome and gives a detailed schedule of planned assessments. These details show what the trial set out to compare and how depressive symptoms were intended to be measured.

They do not provide the primary outcome result. No group means, between-group estimate, confidence interval, or test result for the CDSS is reported in the registry record. Consequently, the direction, size, and precision of a treatment-group difference cannot be described. The absence of a posted comparison does not establish that citalopram and placebo had the same outcome, and it does not establish a benefit or harm. It leaves the comparative outcome unanswered in the reported information.

The trial summary also identifies broader interests in quality of life, relapse, and suicidality, and the registry lists secondary scales covering negative symptoms, psychiatric ratings, suicidal thinking, and quality of life. The presence of an outcome in the registry is not itself a result. The record does not provide comparative findings for those measures in the information.

Safety counts are available, but they are descriptive and lack a reported statistical comparison. They cannot establish treatment causation or the precision of between-group differences. The serious-event term percentages have no stated denominator or arm attribution in the listing. More complete reporting would require group-specific outcome summaries, the analysis definition, uncertainty estimates, and clear information about missing observations and the population analyzed.

Accordingly, the defensible reading is limited: the registry describes the design, the measurement plan, and selected adverse-event counts, but does not report the primary comparative result. No conclusion about whether the groups differed on depression scores or other clinical outcomes follows from the information recorded.

13. Why This Trial Matters Statistically

This trial illustrates the distinction between a registered research question and a reported statistical answer. The record specifies a randomized comparison and a validated symptom scale with repeated assessments, but gives no primary CDSS contrast. Without an estimate and a measure of uncertainty, readers cannot judge the magnitude or precision of any observed difference. A stated aim cannot substitute for the result.

Repeated measurement adds meaningful design and analysis choices. Scores were scheduled over many visits, so a group comparison could focus on one visit, change from baseline, or the overall trajectory. Those alternatives are not interchangeable, and a clear analysis plan is needed to identify the intended estimand and handle within-participant correlation. The registry record does not state the method used.

Likewise, the missing-assessment statement signals that the available observations were not complete at every time point. Without group-specific missingness, reasons, and a missing-data strategy, readers cannot determine how the observed subset relates to the randomized population. The CDSS/CDRS wording inconsistency adds a small but important reporting ambiguity about the measure description.

The record's serious and other adverse-event counts show why descriptive safety summaries need context. Counts are not causal comparisons, and terms presented with percentages need denominators and arm attribution for meaningful interpretation. This record does not report those details for the listed terms or an inferential safety analysis.

Finally, planning illustrations based on an observed effect should not be mistaken for the original sample-size rationale or for evidence that the trial had adequate or inadequate power. Statistical interpretation should focus on estimates and uncertainty, not retrospective power calculations. DECIFER therefore highlights the value of complete outcome reporting, a defined analysis population, transparent handling of missing data, and clear links between trial aims and prespecified analyses.

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 limitations of interpretation arise from the registry information. Although enrollment is recorded as 95, the information does not give a participant flow diagram, arm-specific enrollment totals for the primary outcome, or numbers contributing scores at each visit. The adverse-event at-risk counts do not substitute for outcome follow-up counts.

The primary endpoint schedule covers screening, baseline, weeks 1-8, and later visits through week 52, but there is no identified primary time point or summary measure for a single comparison. No CDSS group summaries or inferential results are reported. The registry's note about incomplete assessments uses the term CDRS, whereas the endpoint is titled CDSS; the discrepancy is not resolved in the record.

Details needed to assess implementation and analysis are also absent, including eligibility criteria beyond the stated conditions, treatment adherence, antipsychotic regimens, randomization procedures, masking roles, and analysis-population definition. Although the summary refers to standardized psychoeducation and the intervention list includes cognitive behavioral therapy and functional magnetic resonance imaging, their operational roles are not described in the information. The relationship of those listed interventions to the randomized comparison is therefore unclear.

The registry names secondary outcomes and records adverse-event counts but does not report comparative results for the secondary measures or statistical tests for safety. It does not report multiplicity handling, missing-data methods, interim analyses, or a statistical analysis plan. These limitations prevent a full appraisal of selective reporting, the stability of estimates, and the scope of conclusions. They are limitations of what is reported in the registry record, not proof that these procedures were absent from the trial itself.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: DECIFER: Depression and Citalopram In First Episode Recovery — NCT01041274.
• Registry record last updated 2019-12-17; status last verified 2019-12.
• Results first posted 2018-11-16.
• 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

DECIFER, also titled Citalopram in First Episode Schizophrenia, is a completed phase 4 randomized, parallel-group trial with quadruple masking. The registry records enrollment of 95 participants with schizophrenia or schizophreniform disorder. The study start is 2010-01 and primary completion is 2014-12.

The comparison was daily flexible-dose citalopram versus daily placebo for 12 months. The primary outcome was the CDSS, a continuous depression-symptom score scheduled for repeated assessment through week 52. Secondary measures named in the record include SANS, BPRS, ISST, and the Heinrich Quality of Life Scale.

The registry does not report a primary outcome analysis or comparative CDSS results. It reports serious adverse events affecting 5 participants in the citalopram group and 4 in the placebo group, and other adverse events affecting 22 and 18, respectively. These figures are descriptive; the record does not provide comparative uncertainty estimates or establish causation.