This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Efficacy of Extended-release Quetiapine (Seroquel XR) as Adjunctive Therapy to Cognitive Behavioral Therapy in the Treat (NCT01971203), a randomized na study. The primary outcome is MADRS.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01971203 |
| Phase | NA |
| Condition | Major Depressive Disorder, Generalized Anxiety Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 62 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Icahn School of Medicine at Mount Sinai |
| Results posted | Yes |
2. Clinical Question
Population
Adults with both major depressive disorder and generalized anxiety disorder were the intended population. The study summary describes adults aged 18–65; the registry reports enrollment of 62 participants.
Intervention
Quetiapine extended-release (Seroquel XR) was given as adjunctive medication with cognitive behavioral therapy (CBT). The arm description gives a target dosage of 150 mg/day, beginning at 50 mg/day, during 16 weeks of treatment including CBT.
Comparator
The comparison group received placebo medication plus CBT. The study summary describes weekly CBT sessions and weekly visits with the study psychiatrist, during which medication was discussed.
Primary question
The intended question was whether adding quetiapine extended-release to CBT produced a different change in depressive symptoms than adding placebo to CBT. Depressive symptoms were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS), with scores at 16 weeks compared with baseline. The registry record does not report a single primary-outcome comparison or its numerical result, so the direction and precision of any difference cannot be determined from the record.
3. Trial Design
The registry describes a randomized, parallel-group study with quadruple masking. Participants were assigned to quetiapine extended-release plus CBT or placebo plus CBT. The registry lists the study as completed and reports enrollment of 62. The phase is recorded as NA. The record gives a start date of 2009-09 and a primary completion date of 2013-06.
The study summary describes a planned treatment period of 16 weeks for approximately 64 adults aged 18–65. It says that CBT sessions were to be held weekly and last about 45 minutes, alongside weekly visits with the study psychiatrist lasting about 20 minutes. These are descriptions of the planned study schedule; the registry record does not report how many sessions each participant attended or how closely treatment followed that schedule.
The intervention was an adjunctive-treatment comparison: both groups received CBT, while the medication assignment differed. The placebo group therefore provides a comparison for the addition of the study medication within this CBT setting, rather than a comparison of CBT with no CBT. The registry does not explain which roles were masked, how randomization was generated or implemented, or whether allocation was concealed. Those design details are not reported in the registry record.
The official title calls the study active controlled, while the listed comparison is placebo plus CBT. The record does not give further detail about that terminology. It also does not report the rationale for the enrollment target, deviations from the planned enrollment, or a prespecified 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.
Before assignment: Ninety-four participants were screened - 10 participants did not meet study eligibility, 22 elected not to continue. 62 participants were randomized, but 7 never returned for the first visit, leaving 55 participants who began treatment.
Overall Study
| Stage | Seroquel XR Plus CBT | Placebo Plus CBT |
|---|---|---|
| STARTED | 26 | 29 |
| COMPLETED | 17 | 21 |
| NOT COMPLETED | 9 | 8 |
Reasons for not completing this period:
| Reason | Seroquel XR Plus CBT | Placebo Plus CBT |
|---|---|---|
| Protocol Violation | 3 | 2 |
| Withdrawal by Subject | 5 | 6 |
| Adverse Event | 1 | 0 |
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.
| Characteristic | Unit | Seroquel XR Plus CBT | Placebo Plus CBT | Total |
|---|---|---|---|---|
| Participants analysed | 30 | 32 | 62 | |
| Age, Continuous | years | 39.93 (SD 13.68) | 39.88 (SD 12.81) | 39.90 (SD 13.12) |
| Sex: Female, Male: Female | Participants | 17 | 21 | 38 |
| Sex: Female, Male: Male | Participants | 13 | 11 | 24 |
| Race/Ethnicity, Customized: White | Participants | 19 | 22 | 41 |
| Race/Ethnicity, Customized: Black | Participants | 4 | 4 | 8 |
| Race/Ethnicity, Customized: Hispanic | Participants | 2 | 3 | 5 |
| Race/Ethnicity, Customized: Asian | Participants | 3 | 1 | 4 |
| Race/Ethnicity, Customized: Other | Participants | 2 | 1 | 3 |
| Race/Ethnicity, Customized: Unknown | Participants | 0 | 1 | 1 |
| Education: Less than HS | Participants | 1 | 0 | 1 |
| Education: HS | Participants | 4 | 2 | 6 |
| Education: Part college | Participants | 3 | 10 | 13 |
| Education: College | Participants | 13 | 15 | 28 |
| Education: Advanced | Participants | 8 | 4 | 12 |
| Education: Unknown | Participants | 1 | 1 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as MADRS, measured over baseline and 16 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was the Montgomery-Åsberg Depression Rating Scale (MADRS), a clinician-administered measure with 10 items. The registry describes its overall score as ranging from 0, indicating normal, to 54, indicating severe depression. In this trial, the stated assessment was the score at 16 weeks compared with baseline.
A depression rating scale provides a structured way to assess symptom severity across participants and over time. A comparison of change can describe whether average scores shifted differently between randomized groups during the study period. Because the MADRS is continuous, results can be summarized using means and standard deviations, as the registry’s outcome description indicates. A mean captures the group’s average score, while a standard deviation describes how spread out individual scores are around that average.
The record does not identify a single summary of the baseline-to-16-week comparison. It notes that the primary outcome had several categories or time points and was not reduced to one comparison. No numerical group means, changes, treatment-effect estimate, or uncertainty interval for the primary outcome are reported in the registry record. The scale’s clinical purpose and range therefore clarify what was intended to be measured, but do not establish the trial’s observed effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The trial was designed to compare two adjunctive strategies: quetiapine extended-release plus CBT and placebo plus CBT. Random assignment is intended to make groups comparable, on average, at the start of a study. The record identifies randomization, but does not report the randomization procedure or the resulting baseline characteristics. The enrolled population was reported as 62, while the summary described approximately 64 adults as the planned study population.
The main outcome was depressive symptom severity measured with MADRS at baseline and 16 weeks. However, the registry record does not provide a single primary-outcome comparison. It explicitly notes that the primary outcome had several categories or time points and was not reduced to one comparison. There are no primary-outcome means, standard deviations, change estimates, confidence intervals, or p-values in the reported details. Consequently, the size, direction, and precision of a between-group difference cannot be assessed from this record.
The record names HAM-A, Clinical Global Impression Scales for Severity and Improvement, and the Changes in Sexual Functioning Questionnaire as secondary outcomes. It reports four outcome measures and zero analyses. The measures’ names indicate that the study addressed anxiety, clinical severity and improvement, and sexual functioning as well as its primary depression measure. Their numerical results are not reported in the registry record, so they cannot resolve the absence of a primary-outcome comparison.
The enrollment count alone does not indicate whether a treatment effect was present or whether an estimate would have been precise. Precision is evaluated from an effect estimate together with its uncertainty, commonly expressed as a confidence interval. Without reported outcome estimates and uncertainty, neither a small nor a large group difference can be established. A missing result is not evidence that the groups were equal, and it is not evidence that one strategy was better.
The registry’s sample-size assumptions describe planning illustrations based on an observed effect, with two-sided significance level 0.05, equal allocation, and a normal approximation. Those illustrations are not observed power and are not the trial’s reported outcome analysis. The record does not report the trial’s own sample-size justification, or enough outcome results to interpret an observed effect. The evidence available from this registry entry is therefore primarily about the question and design, not a quantifiable efficacy result.
9. Statistical Methods Explained
What does randomization contribute?
Randomization assigns participants to study groups using a chance-based process. In general, this helps reduce systematic differences between groups at the start of a trial, including differences that may not have been measured. It does not guarantee identical groups, especially in a study with limited enrollment, and it does not replace the need to describe baseline characteristics or analyze outcomes appropriately. The registry records randomized allocation, but the sequence-generation and allocation procedures are not reported in the registry record.
The parallel-group design means participants were assigned to one treatment group rather than switching between the study treatments. Both groups received CBT; the medication assignment differed. This makes the intended contrast the addition of quetiapine extended-release versus placebo alongside CBT. Any interpretation of that contrast applies to this treatment context, not to medication or CBT considered separately.
What does masking mean?
The registry labels masking as quadruple. Masking is used in general to limit the influence of expectations on treatment delivery, outcome assessment, or participant reports. The registry does not specify which four roles were masked, how masking was maintained, or whether it was successful. Those details should not be inferred from the label alone.
How should a continuous outcome be read?
MADRS is described as a continuous score, and the registry identifies the mean and standard deviation as its summary measures. A mean is the arithmetic average within a group; a standard deviation describes how much individual observations vary around the mean. A difference in means can summarize a group contrast, while the standard deviation alone does not show the estimated treatment effect. Because the planned comparison concerns baseline and 16-week scores, a result might be expressed using endpoint scores, changes from baseline, or another prespecified approach. The registry record does not report which analysis was used.
A confidence interval is a general statistical way to express the uncertainty around an estimate. It gives a range of values compatible with the data and statistical model at a stated confidence level. A narrow interval indicates greater precision than a wide interval, but precision is not the same as clinical importance. No confidence interval for the MADRS comparison is reported in the registry record, so neither precision nor the range of plausible effect sizes can be evaluated.
A p-value, when reported, describes how compatible the data are with a specified null model under the assumptions of the analysis. It does not measure the probability that a treatment works, and it does not describe the size or importance of an effect. The registry record does not report a primary-outcome p-value. It would therefore be inappropriate to characterize the result as statistically significant or not statistically significant.
What do the planning assumptions describe?
The sample-size assumptions are described as planning illustrations based on the observed effect, not as the trial’s own design rationale. They specify a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. The illustration considers detecting a stated fraction of the observed effect. These are assumptions for planning calculations; they do not report the trial’s observed power. The registry record does not report the sample-size justification used to design the trial.
In general, a planning calculation estimates how many participants may be needed to detect an effect under chosen assumptions. Its result depends on the target effect, variability, allocation, significance level, and power target. Such a calculation is not a substitute for the observed outcome analysis. The registry record does not include numerical primary-outcome results from which to assess the observed effect, and no planning figures are reported in the registry entries.
Why does the analysis plan matter?
A prespecified analysis plan identifies the outcome definition, time point, analysis population, handling of missing observations, and statistical model before results are examined. These choices can affect an estimate and its uncertainty. For example, a comparison of final scores adjusted for baseline is not necessarily identical to an unadjusted comparison of change scores. A suitable approach depends on the design, endpoint, and assumptions. The registry record does not report the statistical analysis plan or which model was used.
Multiplicity is also relevant when several outcomes, time points, or comparisons are examined. In general, making many statistical comparisons can increase the chance of at least one apparently unusual result. A prespecified hierarchy or adjustment can address that issue, but the registry record does not report whether either was used. Since the primary endpoint was not reduced to a single comparison and no analyses are listed, the intended multiplicity strategy cannot be evaluated.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures, including MADRS as the primary outcome and HAM-A, Clinical Global Impression Scales for Severity and Improvement, and the Changes in Sexual Functioning Questionnaire as secondary outcomes. It also notes that the primary outcome had several categories or time points and was not reduced to one comparison. This makes it difficult to identify a single primary contrast from the record. The registry reports zero analyses, and does not describe a hierarchy among outcomes, a multiplicity adjustment, or another strategy for interpreting multiple comparisons. Those methods are not reported in the registry record.
When a study examines multiple outcomes or time points, general statistical practice distinguishes prespecified primary comparisons from exploratory ones. Without a clear analysis plan, readers cannot determine which comparison was intended to carry the main inferential weight or how the possibility of chance findings across multiple tests was handled. This is a limitation of what can be interpreted from the record, not evidence that a particular method was or was not used outside it.
The registry record does not report the number of participants with outcome measurements at baseline or 16 weeks, reasons for missing observations, or methods for handling missing data. It also does not identify the analysis population, such as whether analyses included all randomized participants or only those with available measurements. These details matter because incomplete follow-up can affect the estimate when missingness is related to treatment or outcome. Without them, the completeness and analysis of the primary outcome cannot be assessed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Seroquel XR Plus CBT | 0 | 26 | 0.0% |
| Placebo Plus CBT | 0 | 29 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Seroquel XR Plus CBT | 24 of 26 |
| Placebo Plus CBT | 11 of 29 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Seroquel XR Plus CBT | Placebo Plus CBT |
|---|---|---|---|
| Sedation | Nervous system disorders | 24 of 26 | 11 of 29 |
| depression | Psychiatric disorders | 1 of 26 | 0 of 29 |
| Blood clot | Blood and lymphatic system disorders | 1 of 26 | 0 of 29 |
The registry’s serious adverse event fields list 26 participants at risk and 0 affected in the Seroquel XR plus CBT group, and 29 at risk and 0 affected in the placebo plus CBT group. These are the serious-event figures recorded for the groups. The registry does not list any top serious-event terms. Death counts are null, so deaths are not reported in the registry record; null should not be read as a confirmed count of zero.
The separate fields for other adverse events list 26 at risk and 24 affected in the Seroquel XR plus CBT group, and 29 at risk and 11 affected in the placebo plus CBT group. These figures should not be conflated with the serious adverse event fields: they describe a separate category in the record. The registry entry does not provide event terms, severity details, timing, or a narrative explaining these figures.
These counts are descriptive. Without fuller definitions, event-level information, and details of how adverse events were collected and analyzed, they do not establish a causal difference between groups. They also do not provide a complete account of the safety experience. The record’s event figures should be read as registry entries, not as a standalone assessment of the balance of benefits and harms.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, quadruple-masked, parallel-group study was conducted to compare quetiapine extended-release plus CBT with placebo plus CBT in people with major depressive disorder and generalized anxiety disorder. It identifies MADRS at baseline and 16 weeks as the primary endpoint and reports enrollment of 62. These details explain the clinical question and the broad structure of the comparison.
The record does not provide a single primary-outcome comparison or numerical MADRS results. It therefore does not establish the direction or size of a difference between groups, or how precisely any difference was estimated. The absence of a reported analysis cannot be interpreted as a finding of no difference. Nor does it support a conclusion that either adjunctive strategy was superior.
The secondary outcome names indicate that anxiety symptoms, clinical severity and improvement, and sexual functioning were considered. Numerical results for these outcomes are not reported in the registry record. Likewise, the adverse-event entries give group counts but do not include event terms or the additional detail needed to interpret causes, timing, or comparative risk comprehensively.
The study’s question is specific to adding medication or placebo to CBT over the described 16-week treatment period. It does not directly answer how either medication strategy compares with no CBT, how outcomes might differ over a longer period, or how findings apply to people outside the stated population. These are boundaries of the design and record, not claims about the treatment’s effects.
For readers assessing the evidence, the key distinction is between a trial’s design and its reported results. The design can show what comparison was intended; an interpretable treatment effect requires outcome estimates and their uncertainty. Those results are not available in the registry record, so conclusions about efficacy remain undetermined from this entry.
13. Why This Trial Matters Statistically
This trial illustrates why a clearly defined outcome and comparison are central to interpreting a randomized study. The primary question concerns the additional contribution of quetiapine extended-release when CBT is provided in both groups. That is a narrower question than whether the medication works in isolation or whether CBT is effective. Keeping the comparison explicit prevents claims from extending beyond what the design was intended to assess.
The record also shows why identifying the primary estimand and time point matters. MADRS was assessed at baseline and 16 weeks, but the registry notes that the primary outcome had several categories or time points and was not reduced to a single comparison. Without a defined primary contrast, readers cannot identify a reported treatment-effect estimate or judge its uncertainty. A named measure alone is not enough to interpret a result.
Randomization and masking are important design features, but they do not make a missing or unreported analysis interpretable. Assessing a trial also requires information about participant flow, outcome completion, analysis populations, and statistical methods. The registry entry does not report these details, nor does it supply numerical efficacy estimates.
Finally, the safety fields distinguish serious events from other adverse events, but the record provides limited context for either category. This reinforces a general statistical point: counts require clear definitions and appropriate denominators, and descriptive differences should not automatically be treated as causal effects. The trial’s registry record is useful for understanding its planned comparison and reported structure, while its incomplete outcome reporting limits what can be concluded about results.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary limitation for interpreting efficacy is that the registry record does not report a single primary-outcome comparison. Although MADRS and its baseline and 16-week assessments are identified, numerical group results and an effect estimate are not reported. The record also lists zero analyses. As a result, the central clinical question cannot be answered quantitatively from this entry.
Other important reporting details are absent. The registry does not report the randomization procedure, the roles included in quadruple masking, baseline characteristics, participant flow, adherence, or the number of participants with completed outcome measurements. The statistical analysis plan, analysis population, and approach to missing data are also not reported in the registry record. These omissions limit assessment of bias, precision, and the robustness of any analysis.
The record identifies several secondary outcomes but does not give their numerical results or a multiplicity strategy. It also provides adverse-event counts without event terms or fuller context, and deaths are not reported in the registry record. These safety entries cannot stand in for a complete comparative safety analysis.
The study summary describes approximately 64 adults aged 18–65 as the planned population, while the registry reports enrollment of 62. The record does not explain the relationship between the planned and enrolled numbers or describe reasons for any difference. It also does not report the rationale for the enrollment target. Finally, the stated treatment period is 16 weeks; the registry entry does not establish whether the findings, if reported, would apply beyond that period.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy of Extended-release Quetiapine (Seroquel XR) as Adjunctive Therapy to Cognitive Behavioral Therapy in the Treat — NCT01971203.
- Registry record last updated 2018-02-15; status last verified 2018-01.
- Results first posted 2018-02-15.
- 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.
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18. Record Summary
NCT01971203 is a completed randomized, quadruple-masked, parallel-group study of quetiapine extended-release plus CBT versus placebo plus CBT in people with major depressive disorder and generalized anxiety disorder. The registry reports enrollment of 62. The planned treatment period was 16 weeks, and the primary outcome was MADRS assessed at baseline and 16 weeks.
The registry identifies HAM-A, Clinical Global Impression Scales for Severity and Improvement, and the Changes in Sexual Functioning Questionnaire as secondary outcomes. It reports four outcome measures and zero analyses. The primary outcome was not reduced to a single comparison, and numerical efficacy results are not reported in the registry record. Serious adverse event fields list 0 affected in each group; other adverse-event fields list 24 affected in the quetiapine group and 11 in the placebo group. Deaths are not reported in the registry record.