Premenstrual Syndrome
Conditions
Keywords
Premenstrual syndrome, PMS, calcium
Brief summary
The purpose of this study is to compare the efficacy of calcium carbonate to fluoxetine in the treatment of moderate to severe PMS. Second, to compare each active agent to a placebo control. Third, to evaluate the efficacy of each treatment for specific symptom clusters (i.e. affective and somatic). Fourth, to determine whether the addition of calcium to on going fluoxetine treatment leads to additional therapeutic benefit.
Detailed description
This is a double blind, randomized, placebo controlled, parallel study that will randomize 60 women at the Yale site into treatment. Participants will be screened at various collaborating ob-gyn centers for possible PMS symptoms, and direct referrals from the community will also be accepted. Subject participation length is about 7 months with 6 scheduled study visits. Methodology: After successfully completing the screening and qualification phase, participants will be randomized to treatment at Visit 1 for 5 cycles of double-blind treatment. Participants will be evaluated monthly during the randomization phase for adverse events, concurrent medication, and primary and secondary efficacy variables. .
Interventions
DRUGFluoxetine
Fluoxetine 20 mg per day for 4 menstrual cycles. For the fifth menstrual cycle, all women will receive calcium. Women on Fluoxetine will continue taking it in addition to 1200mg of calcium.
DRUGCalcium
1200 mg of calcium to be taken for 5 menstrual cycles.
DRUGPlacebo
For 5 cycles, women will receive placebo. At the end of the fourth cycle, all women will receive 1200 mg of calcium in addition to the placebo medication.
Sponsors
Yale University
Donaghue Medical Research Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 48 Years
Healthy volunteers
No
Inclusion criteria
* Female outpatients between the ages of 18 and 48 who are: * Menstruating * Meet criteria for moderate to severe PMS * Report PMS symptoms for at least 9 our of the 12 months prior to screening; 4) \*Are using an adequate method of birth control.
Exclusion criteria
* Any candidate who: * Fulfills MINI (DSM-IV) criteria for a serious AXIS 1 disorder * Fulfills DSM-IV criteria during the charting phase consistent with a diagnosis of psychotic disorder, bipolar disorder or major depressive disorder * Has a severe, co-existing condition that, in the investigator's opinion, renders the patient unsuitable for the study * Poses a significant risk of suicide * Takes ongoing medication that could treat PMS symptoms * Has a history of hypersensitivity or adverse reaction to fluoxetine or calcium * Is lactating, pregnant or is planning to become pregnant during the course of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of the Change in IDS Symptom Scores Among Groups | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | IDS = Inventory of Depressive Symptomatology: measures depressive symptoms during the previous premenstrual phase with high internal consistency: sum of responses to 28 of 30 possible items each scored 0 to 3 points with total scoring (0=no symptoms, 84=most severe). This outcome is a measure of effect size between the two trial groups and the placebo group, with the placebo effect size value used as a reference. |
| Comparison of the Change in PMTS Symptom Scores Among Groups | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | PMTS = Premenstrual Tension Syndrome (Observer Rating) Scale: a clinician-administered retrospective scale developed for the study of PMS, a sum of responses to 10 items each with 4 points (0=no symptoms, 40=most severe). This outcome is a measure of effect size between the two trial groups and the placebo group, with the placebo effect size value used as a reference. |
| Comparison of the Change in CGI-S Symptom Scores Among Groups | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | CGI-S = Clinical Global Impression-Severity: a severity scale widely used in psychopharmacology research (1=normal not at all ill, 7=among most extremely ill). This outcome is a measure of effect size between the two trial groups and the placebo group, with the placebo effect size value used as a reference. |
| Comparison of the Change in DRSP Symptom Scores Among Groups | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | DRSP = Daily Record of Severity of Problems, which combines responses to 21 items each with scale: 1=no symptoms, 6=extreme. This outcome is a measure of effect size between the two trial groups and the placebo group, with the placebo effect size value used as a reference. |
| Comparison of the Change in CGI Improvement Scores Among Groups | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | CGI-I = Clinical Global Impression Improvement: the improvement subscale of CGI measuring change at each visit as compared to visit 1 (1=very much improved, 7=very much worse). This outcome is a measure of effect size between the two trial groups and the placebo group, with the placebo effect size value used as a reference. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With DRSP LOCF Response to Treatment (50% Improvement) | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | DRSP: Daily Record of Severity of Problems, which combines responses to 21 items each with scale: 1=no symptoms, 6=extreme. LOCF: the last observation carried forward. |
| Proportion of Patients With PMTS Visit-wise Response to Treatment (50% Improvement) | over duration of treatment from baseline to visit 5, including 4 menstrual cycles averaging 4 months after baseline visit | Visit-wise response considers participants who remained in the study until Visit 5 and provided data for the visit. PMTS = Premenstrual Tension Syndrome (Observer Rating) Scale: a clinician-administered retrospective scale developed for the study of PMS, a sum of responses to 10 items each with 4 points (0=no symptoms, 40=most severe). |
| Proportion of Participants With IDS LOCF Response to Treatment (50% Improvement) | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | IDS: Inventory of Depressive Symptomatology: measures depressive symptoms during the previous premenstrual phase with high internal consistency: sum of responses to 28 of 30 possible items each scored 0 to 3 points with total scoring (0=least severe, 84=most severe). LOCF: last observation carried forward. |
| Proportion of Participants With PMTS LOCF Response to Treatment (50% Improvement) | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | PMTS: Premenstrual Tension Syndrome (Observer Rating) Scale: a clinician-administered retrospective scale developed for the study of PMS, a sum of responses to 10 items each with 4 points (0=no symptoms, 40=most severe). LOCF: last observation carried forward. |
| Proportion of Participants With DRSP Visit-wise Response to Treatment (50% Improvement) | over duration of treatment from baseline to visit 5, including 4 menstrual cycles averaging 4 months after baseline visit | Visit-wise response considers participants who remained in the study until Visit 5 and provided data for the visit. DRSP = Daily Record of Severity of Problems, which combines responses to 21 items each with scale: 1=no symptoms, 6=extreme. |
| Proportion of Patients With IDS Visit-wise Response to Treatment (50% Improvement) | over duration of treatment from baseline to visit 5, including 4 menstrual cycles averaging 4 months after baseline visit | Visit-wise response considers participants who remained in the study until Visit 5 and provided data for the visit. IDS = Inventory of Depressive Symptomatology: measures depressive symptoms during the previous premenstrual phase with high internal consistency, sum of responses to 28 of 30 possible items each scored 0 to 3 points with total scoring (0=no symptoms, 84=most severe). |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred through on-site screening in private gynecological practices and community advertisements. Recruitment occurred between 2001-2005 in Providence, Rhode Island and between 2001-2009 in New Haven, Connecticut. Potential subjects provided consent for screening and assessment.
Participants by arm
| Arm | Count |
|---|---|
| I: Fluoxetine Fluoxetine : Fluoxetine 20 mg per day for 4 menstrual cycles. | 13 |
| II: Calcium Calcium : 1200 mg of calcium to be taken for 4 menstrual cycles. | 13 |
| III: Placebo Placebo : For 4 cycles, women will receive placebo. | 13 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 0 |
Baseline characteristics
| Characteristic | I: Fluoxetine | II: Calcium | III: Placebo | Total |
|---|---|---|---|---|
| Age, Customized 25-29 years old | 1 participants | 1 participants | 2 participants | 4 participants |
| Age, Customized 30-39 years old | 11 participants | 6 participants | 7 participants | 24 participants |
| Age, Customized 40-45 years old | 1 participants | 6 participants | 4 participants | 11 participants |
| Baseline Symptom Scores Clinical Global Impression - Severity (CGI-S) | 4.92 units on a scale STANDARD_DEVIATION 0.95 | 4.46 units on a scale STANDARD_DEVIATION 1.27 | 4.15 units on a scale STANDARD_DEVIATION 1.28 | 4.51 units on a scale STANDARD_DEVIATION 0.68 |
| Baseline Symptom Scores Daily Record of Severity of Problems (DRSP) | 2.16 units on a scale STANDARD_DEVIATION 0.86 | 1.12 units on a scale STANDARD_DEVIATION 0.38 | 1.29 units on a scale STANDARD_DEVIATION 0.6 | 1.52 units on a scale STANDARD_DEVIATION 0.37 |
| Baseline Symptom Scores Inventory of Depressive Symptomatology (IDS-C30) | 31.85 units on a scale STANDARD_DEVIATION 9.14 | 30.92 units on a scale STANDARD_DEVIATION 7.62 | 28.85 units on a scale STANDARD_DEVIATION 9.97 | 30.54 units on a scale STANDARD_DEVIATION 5.17 |
| Baseline Symptom Scores Premenstrual Tension Syndrome-Observer (PMTS-O) | 24.15 units on a scale STANDARD_DEVIATION 5.4 | 21.58 units on a scale STANDARD_DEVIATION 3.73 | 20.85 units on a scale STANDARD_DEVIATION 6.62 | 22.19 units on a scale STANDARD_DEVIATION 3.11 |
| Concurrent oral contraceptive use | 4 participants | 3 participants | 3 participants | 10 participants |
| Ever spoken to a doctor about PMS | 4 participants | 5 participants | 6 participants | 15 participants |
| Marital Status Married | 7 participants | 8 participants | 9 participants | 24 participants |
| Marital Status Not collected | 1 participants | 0 participants | 0 participants | 1 participants |
| Marital Status Single/Divorced/Widowed | 5 participants | 5 participants | 4 participants | 14 participants |
| Number of pregnancies 0 pregnancies | 6 participants | 3 participants | 5 participants | 14 participants |
| Number of pregnancies 1 pregnancy | 3 participants | 1 participants | 0 participants | 4 participants |
| Number of pregnancies 2+ pregnancies | 4 participants | 9 participants | 8 participants | 21 participants |
| OB-GYN asked about PMS | 2 participants | 5 participants | 2 participants | 9 participants |
| Race/Ethnicity, Customized Black | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 0 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Not collected | 1 participants | 2 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized Other/Mixed | 2 participants | 1 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized White | 8 participants | 10 participants | 10 participants | 28 participants |
| Region of Enrollment United States | 13 participants | 13 participants | 13 participants | 39 participants |
| Sex: Female, Male Female | 13 Participants | 13 Participants | 13 Participants | 39 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Thought about getting help for PMS | 7 participants | 7 participants | 6 participants | 20 participants |
| Years with PMS >10 years | 3 participants | 5 participants | 6 participants | 14 participants |
| Years with PMS <4 years | 6 participants | 2 participants | 6 participants | 14 participants |
| Years with PMS 5-10 years | 3 participants | 6 participants | 1 participants | 10 participants |
| Years with PMS Number of years not collected | 1 participants | 0 participants | 0 participants | 1 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 10 | 8 / 11 | 2 / 11 |
| serious Total, serious adverse events | 0 / 10 | 0 / 11 | 0 / 11 |
Outcome results
Primary
Comparison of the Change in CGI Improvement Scores Among Groups
CGI-I = Clinical Global Impression Improvement: the improvement subscale of CGI measuring change at each visit as compared to visit 1 (1=very much improved, 7=very much worse). This outcome is a measure of effect size between the two trial groups and the placebo group, with the placebo effect size value used as a reference.
Time frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit
Population: Intention to treat cohort.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| I: Fluoxetine | Comparison of the Change in CGI Improvement Scores Among Groups | Visit 1 | NA units on CGI Improvement scale | — |
| I: Fluoxetine | Comparison of the Change in CGI Improvement Scores Among Groups | Visit 4 | 1.75 units on CGI Improvement scale | Standard Deviation 1.16 |
| I: Fluoxetine | Comparison of the Change in CGI Improvement Scores Among Groups | Visit 3 | 1.67 units on CGI Improvement scale | Standard Deviation 0.87 |
| I: Fluoxetine | Comparison of the Change in CGI Improvement Scores Among Groups | Visit 5 | 1.88 units on CGI Improvement scale | Standard Deviation 0.64 |
| I: Fluoxetine | Comparison of the Change in CGI Improvement Scores Among Groups | Visit 2 | 2.23 units on CGI Improvement scale | Standard Deviation 0.83 |
| II: Calcium | Comparison of the Change in CGI Improvement Scores Among Groups | Visit 5 | 2.45 units on CGI Improvement scale | Standard Deviation 0.82 |
| II: Calcium | Comparison of the Change in CGI Improvement Scores Among Groups | Visit 1 | NA units on CGI Improvement scale | — |
| II: Calcium | Comparison of the Change in CGI Improvement Scores Among Groups | Visit 2 | 3.46 units on CGI Improvement scale | Standard Deviation 0.78 |
| II: Calcium | Comparison of the Change in CGI Improvement Scores Among Groups | Visit 3 | 2.30 units on CGI Improvement scale | Standard Deviation 0.82 |
| II: Calcium | Comparison of the Change in CGI Improvement Scores Among Groups | Visit 4 | 2.36 units on CGI Improvement scale | Standard Deviation 1.03 |
| III: Placebo | Comparison of the Change in CGI Improvement Scores Among Groups | Visit 2 | 3.00 units on CGI Improvement scale | Standard Deviation 1.35 |
| III: Placebo | Comparison of the Change in CGI Improvement Scores Among Groups | Visit 5 | 2.83 units on CGI Improvement scale | Standard Deviation 1.19 |
| III: Placebo | Comparison of the Change in CGI Improvement Scores Among Groups | Visit 4 | 2.77 units on CGI Improvement scale | Standard Deviation 1.17 |
| III: Placebo | Comparison of the Change in CGI Improvement Scores Among Groups | Visit 1 | NA units on CGI Improvement scale | — |
| III: Placebo | Comparison of the Change in CGI Improvement Scores Among Groups | Visit 3 | 3.08 units on CGI Improvement scale | Standard Deviation 1.5 |
p-value: 0.0495% CI: [-1.7, -0.35]Mixed Models Analysis
p-value: 0.5495% CI: [-0.86, 0.46]Mixed Models Analysis
p-value: 0.04Mixed Models Analysis
p-value: 0.54Mixed Models Analysis
Primary
Comparison of the Change in CGI-S Symptom Scores Among Groups
CGI-S = Clinical Global Impression-Severity: a severity scale widely used in psychopharmacology research (1=normal not at all ill, 7=among most extremely ill). This outcome is a measure of effect size between the two trial groups and the placebo group, with the placebo effect size value used as a reference.
Time frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit
Population: Intention to treat cohort.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| I: Fluoxetine | Comparison of the Change in CGI-S Symptom Scores Among Groups | Visit 4 | 2.56 units on CGI-S scale | Standard Deviation 1.13 |
| I: Fluoxetine | Comparison of the Change in CGI-S Symptom Scores Among Groups | Visit 3 | 2.33 units on CGI-S scale | Standard Deviation 1 |
| I: Fluoxetine | Comparison of the Change in CGI-S Symptom Scores Among Groups | Visit 1 | 4.92 units on CGI-S scale | Standard Deviation 0.95 |
| I: Fluoxetine | Comparison of the Change in CGI-S Symptom Scores Among Groups | Visit 2 | 2.54 units on CGI-S scale | Standard Deviation 1.13 |
| I: Fluoxetine | Comparison of the Change in CGI-S Symptom Scores Among Groups | Visit 5 | 2.50 units on CGI-S scale | Standard Deviation 0.76 |
| II: Calcium | Comparison of the Change in CGI-S Symptom Scores Among Groups | Visit 3 | 3.00 units on CGI-S scale | Standard Deviation 1.1 |
| II: Calcium | Comparison of the Change in CGI-S Symptom Scores Among Groups | Visit 1 | 4.46 units on CGI-S scale | Standard Deviation 1.27 |
| II: Calcium | Comparison of the Change in CGI-S Symptom Scores Among Groups | Visit 2 | 4.23 units on CGI-S scale | Standard Deviation 1.01 |
| II: Calcium | Comparison of the Change in CGI-S Symptom Scores Among Groups | Visit 4 | 2.73 units on CGI-S scale | Standard Deviation 0.9 |
| II: Calcium | Comparison of the Change in CGI-S Symptom Scores Among Groups | Visit 5 | 2.91 units on CGI-S scale | Standard Deviation 1.04 |
| III: Placebo | Comparison of the Change in CGI-S Symptom Scores Among Groups | Visit 5 | 3.17 units on CGI-S scale | Standard Deviation 1.47 |
| III: Placebo | Comparison of the Change in CGI-S Symptom Scores Among Groups | Visit 4 | 2.92 units on CGI-S scale | Standard Deviation 1.5 |
| III: Placebo | Comparison of the Change in CGI-S Symptom Scores Among Groups | Visit 1 | 4.15 units on CGI-S scale | Standard Deviation 1.28 |
| III: Placebo | Comparison of the Change in CGI-S Symptom Scores Among Groups | Visit 3 | 3.38 units on CGI-S scale | Standard Deviation 1.98 |
| III: Placebo | Comparison of the Change in CGI-S Symptom Scores Among Groups | Visit 2 | 3.38 units on CGI-S scale | Standard Deviation 1.66 |
p-value: 0.0795% CI: [-0.73, 0.03]Mixed Models Analysis
p-value: 0.3695% CI: [-0.54, 0.2]Mixed Models Analysis
p-value: 0.07Mixed Models Analysis
p-value: 0.36Mixed Models Analysis
Primary
Comparison of the Change in DRSP Symptom Scores Among Groups
DRSP = Daily Record of Severity of Problems, which combines responses to 21 items each with scale: 1=no symptoms, 6=extreme. This outcome is a measure of effect size between the two trial groups and the placebo group, with the placebo effect size value used as a reference.
Time frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit
Population: Intention to treat cohort.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| I: Fluoxetine | Comparison of the Change in DRSP Symptom Scores Among Groups | Visit 4 | 0.72 units on DRSP scale | Standard Deviation 0.78 |
| I: Fluoxetine | Comparison of the Change in DRSP Symptom Scores Among Groups | Visit 3 | 0.27 units on DRSP scale | Standard Deviation 0.78 |
| I: Fluoxetine | Comparison of the Change in DRSP Symptom Scores Among Groups | Visit 1 | 2.16 units on DRSP scale | Standard Deviation 0.86 |
| I: Fluoxetine | Comparison of the Change in DRSP Symptom Scores Among Groups | Visit 2 | 0.97 units on DRSP scale | Standard Deviation 0.72 |
| I: Fluoxetine | Comparison of the Change in DRSP Symptom Scores Among Groups | Visit 5 | 0.44 units on DRSP scale | Standard Deviation 0.34 |
| II: Calcium | Comparison of the Change in DRSP Symptom Scores Among Groups | Visit 3 | 0.61 units on DRSP scale | Standard Deviation 0.78 |
| II: Calcium | Comparison of the Change in DRSP Symptom Scores Among Groups | Visit 1 | 1.12 units on DRSP scale | Standard Deviation 0.38 |
| II: Calcium | Comparison of the Change in DRSP Symptom Scores Among Groups | Visit 2 | 0.76 units on DRSP scale | Standard Deviation 0.78 |
| II: Calcium | Comparison of the Change in DRSP Symptom Scores Among Groups | Visit 4 | 0.51 units on DRSP scale | Standard Deviation 0.33 |
| II: Calcium | Comparison of the Change in DRSP Symptom Scores Among Groups | Visit 5 | 0.75 units on DRSP scale | Standard Deviation 0.42 |
| III: Placebo | Comparison of the Change in DRSP Symptom Scores Among Groups | Visit 5 | 0.74 units on DRSP scale | Standard Deviation 0.54 |
| III: Placebo | Comparison of the Change in DRSP Symptom Scores Among Groups | Visit 4 | 0.59 units on DRSP scale | Standard Deviation 0.63 |
| III: Placebo | Comparison of the Change in DRSP Symptom Scores Among Groups | Visit 1 | 1.29 units on DRSP scale | Standard Deviation 0.6 |
| III: Placebo | Comparison of the Change in DRSP Symptom Scores Among Groups | Visit 3 | 1.19 units on DRSP scale | Standard Deviation 1.06 |
| III: Placebo | Comparison of the Change in DRSP Symptom Scores Among Groups | Visit 2 | 0.93 units on DRSP scale | Standard Deviation 0.54 |
p-value: 0.0295% CI: [-0.53, -0.04]Mixed Models Analysis
p-value: 0.5895% CI: [-0.16, 0.28]Mixed Models Analysis
p-value: 0.02Mixed Models Analysis
p-value: 0.58Mixed Models Analysis
Primary
Comparison of the Change in IDS Symptom Scores Among Groups
IDS = Inventory of Depressive Symptomatology: measures depressive symptoms during the previous premenstrual phase with high internal consistency: sum of responses to 28 of 30 possible items each scored 0 to 3 points with total scoring (0=no symptoms, 84=most severe). This outcome is a measure of effect size between the two trial groups and the placebo group, with the placebo effect size value used as a reference.
Time frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit
Population: Intention to treat cohort.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| I: Fluoxetine | Comparison of the Change in IDS Symptom Scores Among Groups | Visit 4 | 11.78 units on IDS scale | Standard Deviation 8.5 |
| I: Fluoxetine | Comparison of the Change in IDS Symptom Scores Among Groups | Visit 3 | 11.44 units on IDS scale | Standard Deviation 7.94 |
| I: Fluoxetine | Comparison of the Change in IDS Symptom Scores Among Groups | Visit 1 | 31.85 units on IDS scale | Standard Deviation 9.14 |
| I: Fluoxetine | Comparison of the Change in IDS Symptom Scores Among Groups | Visit 2 | 14.08 units on IDS scale | Standard Deviation 9.53 |
| I: Fluoxetine | Comparison of the Change in IDS Symptom Scores Among Groups | Visit 5 | 10.00 units on IDS scale | Standard Deviation 6.41 |
| II: Calcium | Comparison of the Change in IDS Symptom Scores Among Groups | Visit 3 | 18.55 units on IDS scale | Standard Deviation 10.4 |
| II: Calcium | Comparison of the Change in IDS Symptom Scores Among Groups | Visit 1 | 30.92 units on IDS scale | Standard Deviation 7.62 |
| II: Calcium | Comparison of the Change in IDS Symptom Scores Among Groups | Visit 2 | 25.77 units on IDS scale | Standard Deviation 7.74 |
| II: Calcium | Comparison of the Change in IDS Symptom Scores Among Groups | Visit 4 | 18.50 units on IDS scale | Standard Deviation 9.01 |
| II: Calcium | Comparison of the Change in IDS Symptom Scores Among Groups | Visit 5 | 19.55 units on IDS scale | Standard Deviation 9.04 |
| III: Placebo | Comparison of the Change in IDS Symptom Scores Among Groups | Visit 5 | 18.08 units on IDS scale | Standard Deviation 9.17 |
| III: Placebo | Comparison of the Change in IDS Symptom Scores Among Groups | Visit 4 | 16.46 units on IDS scale | Standard Deviation 11 |
| III: Placebo | Comparison of the Change in IDS Symptom Scores Among Groups | Visit 1 | 28.85 units on IDS scale | Standard Deviation 9.97 |
| III: Placebo | Comparison of the Change in IDS Symptom Scores Among Groups | Visit 3 | 20.15 units on IDS scale | Standard Deviation 14.25 |
| III: Placebo | Comparison of the Change in IDS Symptom Scores Among Groups | Visit 2 | 20.69 units on IDS scale | Standard Deviation 12.2 |
p-value: 0.0795% CI: [-5.51, 0.24]Mixed Models Analysis
p-value: 0.9495% CI: [-2.85, 2.65]Mixed Models Analysis
p-value: 0.07Mixed Models Analysis
p-value: 0.94Mixed Models Analysis
Primary
Comparison of the Change in PMTS Symptom Scores Among Groups
PMTS = Premenstrual Tension Syndrome (Observer Rating) Scale: a clinician-administered retrospective scale developed for the study of PMS, a sum of responses to 10 items each with 4 points (0=no symptoms, 40=most severe). This outcome is a measure of effect size between the two trial groups and the placebo group, with the placebo effect size value used as a reference.
Time frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit
Population: Intention to treat cohort.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| I: Fluoxetine | Comparison of the Change in PMTS Symptom Scores Among Groups | Visit 4 | 12.11 units on PMTS scale | Standard Deviation 7.13 |
| I: Fluoxetine | Comparison of the Change in PMTS Symptom Scores Among Groups | Visit 3 | 10.33 units on PMTS scale | Standard Deviation 6.4 |
| I: Fluoxetine | Comparison of the Change in PMTS Symptom Scores Among Groups | Visit 1 | 24.15 units on PMTS scale | Standard Deviation 5.4 |
| I: Fluoxetine | Comparison of the Change in PMTS Symptom Scores Among Groups | Visit 2 | 11.15 units on PMTS scale | Standard Deviation 5.77 |
| I: Fluoxetine | Comparison of the Change in PMTS Symptom Scores Among Groups | Visit 5 | 10.13 units on PMTS scale | Standard Deviation 3.56 |
| II: Calcium | Comparison of the Change in PMTS Symptom Scores Among Groups | Visit 3 | 13.36 units on PMTS scale | Standard Deviation 5.75 |
| II: Calcium | Comparison of the Change in PMTS Symptom Scores Among Groups | Visit 1 | 21.58 units on PMTS scale | Standard Deviation 3.73 |
| II: Calcium | Comparison of the Change in PMTS Symptom Scores Among Groups | Visit 2 | 18.54 units on PMTS scale | Standard Deviation 5.36 |
| II: Calcium | Comparison of the Change in PMTS Symptom Scores Among Groups | Visit 4 | 12.83 units on PMTS scale | Standard Deviation 4.73 |
| II: Calcium | Comparison of the Change in PMTS Symptom Scores Among Groups | Visit 5 | 11.91 units on PMTS scale | Standard Deviation 4.48 |
| III: Placebo | Comparison of the Change in PMTS Symptom Scores Among Groups | Visit 5 | 14.58 units on PMTS scale | Standard Deviation 7.58 |
| III: Placebo | Comparison of the Change in PMTS Symptom Scores Among Groups | Visit 4 | 12.77 units on PMTS scale | Standard Deviation 8.21 |
| III: Placebo | Comparison of the Change in PMTS Symptom Scores Among Groups | Visit 1 | 20.85 units on PMTS scale | Standard Deviation 6.62 |
| III: Placebo | Comparison of the Change in PMTS Symptom Scores Among Groups | Visit 3 | 16.38 units on PMTS scale | Standard Deviation 10.52 |
| III: Placebo | Comparison of the Change in PMTS Symptom Scores Among Groups | Visit 2 | 16.00 units on PMTS scale | Standard Deviation 8.15 |
p-value: 0.195% CI: [-3.6, 0.34]Mixed Models Analysis
p-value: 0.495% CI: [-2.71, 1.09]Mixed Models Analysis
p-value: 0.1Mixed Models Analysis
p-value: 0.4Mixed Models Analysis
Secondary
Proportion of Participants With DRSP LOCF Response to Treatment (50% Improvement)
DRSP: Daily Record of Severity of Problems, which combines responses to 21 items each with scale: 1=no symptoms, 6=extreme. LOCF: the last observation carried forward.
Time frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit
Population: Response analysis includes all data from all subjects with the last observation carried forward to Visit 5.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| I: Fluoxetine | Proportion of Participants With DRSP LOCF Response to Treatment (50% Improvement) | 0.80 proportion of participants |
| II: Calcium | Proportion of Participants With DRSP LOCF Response to Treatment (50% Improvement) | 0.42 proportion of participants |
| III: Placebo | Proportion of Participants With DRSP LOCF Response to Treatment (50% Improvement) | 0.42 proportion of participants |
p-value: 0.15Chi-squared
Secondary
Proportion of Participants With DRSP Visit-wise Response to Treatment (50% Improvement)
Visit-wise response considers participants who remained in the study until Visit 5 and provided data for the visit. DRSP = Daily Record of Severity of Problems, which combines responses to 21 items each with scale: 1=no symptoms, 6=extreme.
Time frame: over duration of treatment from baseline to visit 5, including 4 menstrual cycles averaging 4 months after baseline visit
Population: For fluoxetine, calcium and placebo groups, 8, 11 and 12 participants remained in the trial until Visit 5. However, Visit 5 DRSP calendars were missing for an additional 3 subjects in the fluoxetine group and for one subject in each of the calcium and placebo cells.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| I: Fluoxetine | Proportion of Participants With DRSP Visit-wise Response to Treatment (50% Improvement) | 1.00 proportion of participants |
| II: Calcium | Proportion of Participants With DRSP Visit-wise Response to Treatment (50% Improvement) | 0.50 proportion of participants |
| III: Placebo | Proportion of Participants With DRSP Visit-wise Response to Treatment (50% Improvement) | 0.33 proportion of participants |
p-value: 0.09Chi-squared
Secondary
Proportion of Participants With IDS LOCF Response to Treatment (50% Improvement)
IDS: Inventory of Depressive Symptomatology: measures depressive symptoms during the previous premenstrual phase with high internal consistency: sum of responses to 28 of 30 possible items each scored 0 to 3 points with total scoring (0=least severe, 84=most severe). LOCF: last observation carried forward.
Time frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit
Population: Response analysis includes all data from all subjects with the last observation carried forward to Visit 5.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| I: Fluoxetine | Proportion of Participants With IDS LOCF Response to Treatment (50% Improvement) | 0.77 proportion of participants |
| II: Calcium | Proportion of Participants With IDS LOCF Response to Treatment (50% Improvement) | 0.31 proportion of participants |
| III: Placebo | Proportion of Participants With IDS LOCF Response to Treatment (50% Improvement) | 0.31 proportion of participants |
p-value: 0.05Chi-squared
Secondary
Proportion of Participants With PMTS LOCF Response to Treatment (50% Improvement)
PMTS: Premenstrual Tension Syndrome (Observer Rating) Scale: a clinician-administered retrospective scale developed for the study of PMS, a sum of responses to 10 items each with 4 points (0=no symptoms, 40=most severe). LOCF: last observation carried forward.
Time frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit
Population: Response analysis includes all data from all subjects with the last observation carried forward to Visit 5.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| I: Fluoxetine | Proportion of Participants With PMTS LOCF Response to Treatment (50% Improvement) | 0.62 proportion of participants |
| II: Calcium | Proportion of Participants With PMTS LOCF Response to Treatment (50% Improvement) | 0.33 proportion of participants |
| III: Placebo | Proportion of Participants With PMTS LOCF Response to Treatment (50% Improvement) | 0.16 proportion of participants |
p-value: 0.06Chi-squared
Secondary
Proportion of Patients With IDS Visit-wise Response to Treatment (50% Improvement)
Visit-wise response considers participants who remained in the study until Visit 5 and provided data for the visit. IDS = Inventory of Depressive Symptomatology: measures depressive symptoms during the previous premenstrual phase with high internal consistency, sum of responses to 28 of 30 possible items each scored 0 to 3 points with total scoring (0=no symptoms, 84=most severe).
Time frame: over duration of treatment from baseline to visit 5, including 4 menstrual cycles averaging 4 months after baseline visit
Population: For fluoxetine, calcium and placebo groups, 8, 11 and 12 participants remained in the trial until Visit 5.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| I: Fluoxetine | Proportion of Patients With IDS Visit-wise Response to Treatment (50% Improvement) | 1.00 proportion of participants |
| II: Calcium | Proportion of Patients With IDS Visit-wise Response to Treatment (50% Improvement) | 0.36 proportion of participants |
| III: Placebo | Proportion of Patients With IDS Visit-wise Response to Treatment (50% Improvement) | 0.33 proportion of participants |
p-value: 0.005Chi-squared
Secondary
Proportion of Patients With PMTS Visit-wise Response to Treatment (50% Improvement)
Visit-wise response considers participants who remained in the study until Visit 5 and provided data for the visit. PMTS = Premenstrual Tension Syndrome (Observer Rating) Scale: a clinician-administered retrospective scale developed for the study of PMS, a sum of responses to 10 items each with 4 points (0=no symptoms, 40=most severe).
Time frame: over duration of treatment from baseline to visit 5, including 4 menstrual cycles averaging 4 months after baseline visit
Population: For fluoxetine, calcium and placebo groups, 8, 11 and 12 participants remained in the trial until Visit 5.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| I: Fluoxetine | Proportion of Patients With PMTS Visit-wise Response to Treatment (50% Improvement) | 0.75 proportion of participants |
| II: Calcium | Proportion of Patients With PMTS Visit-wise Response to Treatment (50% Improvement) | 0.36 proportion of participants |
| III: Placebo | Proportion of Patients With PMTS Visit-wise Response to Treatment (50% Improvement) | 0.17 proportion of participants |
p-value: 0.04Chi-squared