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Comparison of Fluoxetine, Calcium and Placebo for the Treatment of Moderate to Severe Premenstrual Syndrome (PMS)

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ClinicalTrials.gov Identifier: NCT00965562
Recruitment Status : Completed
First Posted : August 25, 2009
Results First Posted : February 26, 2015
Last Update Posted : March 23, 2015
Sponsor:
Collaborator:
Yale University
Information provided by (Responsible Party):
Kimberly Yonkers, Yale University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Premenstrual Syndrome
Interventions Drug: Fluoxetine
Drug: Calcium
Drug: Placebo
Enrollment 49
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.
Pre-assignment Details  
Arm/Group Title I: Fluoxetine II: Calcium III: Placebo
Hide Arm/Group Description Fluoxetine : Fluoxetine 20 mg per day for 4 menstrual cycles. Calcium : 1200 mg of calcium to be taken for 4 menstrual cycles. Placebo : For 4 cycles, women will receive placebo.
Period Title: Overall Study
Started 16 17 16
Women With at Least 2 Follow up Visits 13 [1] 13 [2] 13 [3]
Women Who Participated Full Follow up 6 [4] 10 [5] 11 [6]
Completed 13 [7] 13 [7] 13 [7]
Not Completed 3 4 3
Reason Not Completed
Lost to Follow-up             1             2             3
Withdrawal by Subject             2             2             0
[1]
3 patients with no follow up visits: 1 out of contact, 2 patient requests
[2]
4 patients with no follow up visits: 2 out of contact, 2 patient requests
[3]
3 patients with no follow up visits: 3 out of contact
[4]
7 patients discontinued intervention: 2 out of contact, 4 patient requests, 1 suspended by IRB
[5]
3 patients discontinued intervention: 1 out of contact, 2 patient requests
[6]
2 patients discontinued intervention: 2 patient requests
[7]
Participants who completed at least 2 visits were analyzed.
Arm/Group Title I: Fluoxetine II: Calcium III: Placebo Total
Hide Arm/Group Description Fluoxetine : Fluoxetine 20 mg per day for 4 menstrual cycles. Calcium : 1200 mg of calcium to be taken for 4 menstrual cycles. Placebo : For 4 cycles, women will receive placebo. Total of all reporting groups
Overall Number of Baseline Participants 13 13 13 39
Hide Baseline Analysis Population Description
Participants with at least 2 follow up visits were included in analysis.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 13 participants 39 participants
25-29 years old 1 1 2 4
30-39 years old 11 6 7 24
40-45 years old 1 6 4 11
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 13 participants 39 participants
Female
13
 100.0%
13
 100.0%
13
 100.0%
39
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 13 participants 39 participants
White 8 10 10 28
Black 1 0 0 1
Hispanic 1 0 1 2
Other/Mixed 2 1 1 4
Not collected 1 2 1 4
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 13 participants 13 participants 13 participants 39 participants
13 13 13 39
Marital Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 13 participants 39 participants
Married 7 8 9 24
Single/Divorced/Widowed 5 5 4 14
Not collected 1 0 0 1
Number of pregnancies  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 13 participants 39 participants
0 pregnancies 6 3 5 14
1 pregnancy 3 1 0 4
2+ pregnancies 4 9 8 21
Years with PMS   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 13 participants 39 participants
<4 years 6 2 6 14
5-10 years 3 6 1 10
>10 years 3 5 6 14
Number of years not collected 1 0 0 1
[1]
Measure Description: PMS= premenstrual syndrome.
Ever spoken to a doctor about PMS   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 13 participants 39 participants
4 5 6 15
[1]
Measure Description: PMS= premenstrual syndrome. Only participants who indicated that they had spoken to a doctor about their PMS were included in this affirmative measure.
OB-GYN asked about PMS   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 13 participants 39 participants
2 5 2 9
[1]
Measure Description: PMS= premenstrual syndrome. Only participants who indicated that their OB-GYN had asked about PMS were included in this affirmative measure.
Thought about getting help for PMS   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 13 participants 39 participants
7 7 6 20
[1]
Measure Description: PMS= premenstrual syndrome. Only participants who indicated that they had thought about getting help for their PMS symptoms were included in this affirmative measure.
Concurrent oral contraceptive use   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 13 participants 39 participants
4 3 3 10
[1]
Measure Description: Only participants who indicated that they were concurrently taking contraceptives were included in this affirmative measure.
Baseline Symptom Scores   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 13 participants 13 participants 13 participants 39 participants
Inventory of Depressive Symptomatology (IDS-C30) 31.85  (9.14) 30.92  (7.62) 28.85  (9.97) 30.54  (5.17)
Premenstrual Tension Syndrome-Observer (PMTS-O) 24.15  (5.40) 21.58  (3.73) 20.85  (6.62) 22.19  (3.11)
Daily Record of Severity of Problems (DRSP) 2.16  (0.86) 1.12  (0.38) 1.29  (0.60) 1.52  (0.37)
Clinical Global Impression - Severity (CGI-S) 4.92  (0.95) 4.46  (1.27) 4.15  (1.28) 4.51  (0.68)
[1]
Measure Description: IDS= sum of responses to 28 of 30 possible items each scored 0 to 3 points (0=least severe 84= most severe); PMTS= total score 10 items, each with 4 points (0 is no symptom and 40 total = most severe); CGI-S= illness severity (1=normal 7=among most critically ill) . The IDS, PMTS, and CGI-S were scored on the basis of severity during the prior premenstrual phase. DRSP= 21 items each with scale (1=no symptom 6=extreme); The DRSP score was generated by subtracting average follicular phase severity from average luteal phase severity, and averaging these phase change means across symptoms.
1.Primary Outcome
Title Comparison of the Change in IDS Symptom Scores Among Groups
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to treat cohort.
Arm/Group Title I: Fluoxetine II: Calcium III: Placebo
Hide Arm/Group Description:
Fluoxetine : Fluoxetine 20 mg per day for 4 menstrual cycles.
Calcium : 1200 mg of calcium to be taken for 4 menstrual cycles.
Placebo : For 4 cycles, women will receive placebo.
Overall Number of Participants Analyzed 13 13 13
Mean (Standard Deviation)
Unit of Measure: units on IDS scale
Visit 1 31.85  (9.14) 30.92  (7.62) 28.85  (9.97)
Visit 2 14.08  (9.53) 25.77  (7.74) 20.69  (12.20)
Visit 3 11.44  (7.94) 18.55  (10.40) 20.15  (14.25)
Visit 4 11.78  (8.50) 18.50  (9.01) 16.46  (11.00)
Visit 5 10.00  (6.41) 19.55  (9.04) 18.08  (9.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -2.63
Confidence Interval (2-Sided) 95%
-5.51 to 0.24
Estimation Comments Slope represents average change in fluoxetine group IDS score as compared to placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-2.85 to 2.65
Estimation Comments Slope represents average change in calcium group IDS scores as compared to placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cohen's d effect size
Estimated Value 1.15
Estimation Comments Cohen's d effect sizes were calculated by subtracting the difference between changes in the fluoxetine group between visits 1 and 5 and changes in the placebo group between Visits 1 and 5, divided by the std dev in the placebo group at Visit 5
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cohen's d effect size
Estimated Value 0.10
Estimation Comments Cohen's d effect sizes were calculated by subtracting the difference between changes in the calcium group between visits 1 and 5 and changes in the placebo group between Visits 1 and 5, divided by the std dev in the placebo group at Visit 5
2.Primary Outcome
Title Comparison of the Change in PMTS Symptom Scores Among Groups
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to treat cohort.
Arm/Group Title I: Fluoxetine II: Calcium III: Placebo
Hide Arm/Group Description:
Fluoxetine : Fluoxetine 20 mg per day for 4 menstrual cycles.
Calcium : 1200 mg of calcium to be taken for 4 menstrual cycles.
Placebo : For 4 cycles, women will receive placebo.
Overall Number of Participants Analyzed 13 13 13
Mean (Standard Deviation)
Unit of Measure: units on PMTS scale
Visit 1 24.15  (5.40) 21.58  (3.73) 20.85  (6.62)
Visit 2 11.15  (5.77) 18.54  (5.36) 16.00  (8.15)
Visit 3 10.33  (6.40) 13.36  (5.75) 16.38  (10.52)
Visit 4 12.11  (7.13) 12.83  (4.73) 12.77  (8.21)
Visit 5 10.13  (3.56) 11.91  (4.48) 14.58  (7.58)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.10
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -1.63
Confidence Interval (2-Sided) 95%
-3.60 to 0.34
Estimation Comments Slope represents average change in fluoxetine group PMTS scores as compared to placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.40
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.81
Confidence Interval (2-Sided) 95%
-2.71 to 1.09
Estimation Comments Slope represents average change in calcium group PMTS scores as compared to placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.10
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cohen's d effect size
Estimated Value 1.06
Estimation Comments Cohen's d effect sizes were calculated by subtracting the difference between changes in the fluoxetine group between visits 1 and 5 and changes in the placebo group between Visits 1 and 5, divided by the std dev in the placebo group at Visit 5
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.40
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cohen's d effect size
Estimated Value 0.37
Estimation Comments Cohen's d effect sizes were calculated by subtracting the difference between changes in the calcium group between visits 1 and 5 and changes in the placebo group between Visits 1 and 5, divided by the std dev in the placebo group at Visit 5
3.Primary Outcome
Title Comparison of the Change in CGI-S Symptom Scores Among Groups
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to treat cohort.
Arm/Group Title I: Fluoxetine II: Calcium III: Placebo
Hide Arm/Group Description:
Fluoxetine : Fluoxetine 20 mg per day for 4 menstrual cycles.
Calcium : 1200 mg of calcium to be taken for 4 menstrual cycles.
Placebo : For 4 cycles, women will receive placebo.
Overall Number of Participants Analyzed 13 13 13
Mean (Standard Deviation)
Unit of Measure: units on CGI-S scale
Visit 1 4.92  (0.95) 4.46  (1.27) 4.15  (1.28)
Visit 2 2.54  (1.13) 4.23  (1.01) 3.38  (1.66)
Visit 3 2.33  (1.00) 3.00  (1.10) 3.38  (1.98)
Visit 4 2.56  (1.13) 2.73  (0.90) 2.92  (1.50)
Visit 5 2.50  (0.76) 2.91  (1.04) 3.17  (1.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-0.73 to 0.03
Estimation Comments Slope represents average change in fluoxetine group CGI-S scores as compared to placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.36
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.54 to 0.20
Estimation Comments Slope represents average change in calcium group CGI-S scores as compared to placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cohen's d effect size
Estimated Value 0.92
Estimation Comments Cohen's d effect sizes were calculated by subtracting the difference between changes in the fluoxetine group between visits 1 and 5 and changes in the placebo group between Visits 1 and 5, divided by the std dev in the placebo group at Visit 5
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.36
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cohen's d effect size
Estimated Value 0.44
Estimation Comments Cohen's d effect sizes were calculated by subtracting the difference between changes in the calcium group between visits 1 and 5 and changes in the placebo group between Visits 1 and 5, divided by the std dev in the placebo group at Visit 5
4.Primary Outcome
Title Comparison of the Change in DRSP Symptom Scores Among Groups
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to treat cohort.
Arm/Group Title I: Fluoxetine II: Calcium III: Placebo
Hide Arm/Group Description:
Fluoxetine : Fluoxetine 20 mg per day for 4 menstrual cycles.
Calcium : 1200 mg of calcium to be taken for 4 menstrual cycles.
Placebo : For 4 cycles, women will receive placebo.
Overall Number of Participants Analyzed 13 13 13
Mean (Standard Deviation)
Unit of Measure: units on DRSP scale
Visit 1 2.16  (0.86) 1.12  (0.38) 1.29  (0.60)
Visit 2 0.97  (0.72) 0.76  (0.78) 0.93  (0.54)
Visit 3 0.27  (0.78) 0.61  (0.78) 1.19  (1.06)
Visit 4 0.72  (0.78) 0.51  (0.33) 0.59  (0.63)
Visit 5 0.44  (0.34) 0.75  (0.42) 0.74  (0.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.53 to -0.04
Estimation Comments Slope represents average change in fluoxetine group DRSP scores as compared to placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.58
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.16 to 0.28
Estimation Comments Slope represents average change in calcium group DRSP scores as compared to placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cohen's d effect size
Estimated Value 2.08
Estimation Comments Cohen's d effect sizes were calculated by subtracting the difference between changes in the fluoxetine group between visits 1 and 5 and changes in the placebo group between Visits 1 and 5, divided by the std dev in the placebo group at Visit 5
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.58
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cohen's d effect size
Estimated Value 0.18
Estimation Comments Cohen's d effect sizes were calculated by subtracting the difference between changes in the calcium group between visits 1 and 5 and changes in the placebo group between Visits 1 and 5, divided by the std dev in the placebo group at Visit 5
5.Primary Outcome
Title Comparison of the Change in CGI Improvement Scores Among Groups
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to treat cohort.
Arm/Group Title I: Fluoxetine II: Calcium III: Placebo
Hide Arm/Group Description:
Fluoxetine : Fluoxetine 20 mg per day for 4 menstrual cycles.
Calcium : 1200 mg of calcium to be taken for 4 menstrual cycles.
Placebo : For 4 cycles, women will receive placebo.
Overall Number of Participants Analyzed 13 13 13
Mean (Standard Deviation)
Unit of Measure: units on CGI Improvement scale
Visit 1 NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Visit 2 2.23  (0.83) 3.46  (0.78) 3.00  (1.35)
Visit 3 1.67  (0.87) 2.30  (0.82) 3.08  (1.50)
Visit 4 1.75  (1.16) 2.36  (1.03) 2.77  (1.17)
Visit 5 1.88  (0.64) 2.45  (0.82) 2.83  (1.19)
[1]
at first visit, improvement since last visit cannot be scored
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -1.03
Confidence Interval (2-Sided) 95%
-1.70 to -0.35
Estimation Comments Slope represents average change in fluoxetine group CGI Improvement scores as compared to placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.54
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-0.86 to 0.46
Estimation Comments Slope represents average change in calcium group CGI Improvement scores as compared to placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cohen's d effect size
Estimated Value 0.80
Estimation Comments Cohen's d effect sizes were calculated by subtracting the difference between changes in the fluoxetine group between visits 2 and 5 and changes in the placebo group between Visits 2 and 5, divided by the std dev in the placebo group at Visit 5
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.54
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cohen's d effect size
Estimated Value 0.32
Estimation Comments Cohen's d effect sizes were calculated by subtracting the difference between changes in the calcium group between visits 2 and 5 and changes in the placebo group between Visits 2 and 5, divided by the std dev in the placebo group at Visit 5
6.Secondary Outcome
Title Proportion of Participants With DRSP LOCF Response to Treatment (50% Improvement)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Response analysis includes all data from all subjects with the last observation carried forward to Visit 5.
Arm/Group Title I: Fluoxetine II: Calcium III: Placebo
Hide Arm/Group Description:
Fluoxetine : Fluoxetine 20 mg per day for 4 menstrual cycles.
Calcium : 1200 mg of calcium to be taken for 4 menstrual cycles.
Placebo : For 4 cycles, women will receive placebo.
Overall Number of Participants Analyzed 10 12 12
Measure Type: Number
Unit of Measure: proportion of participants
0.80 0.42 0.42
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
7.Secondary Outcome
Title Proportion of Participants With IDS LOCF Response to Treatment (50% Improvement)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Response analysis includes all data from all subjects with the last observation carried forward to Visit 5.
Arm/Group Title I: Fluoxetine II: Calcium III: Placebo
Hide Arm/Group Description:
Fluoxetine : Fluoxetine 20 mg per day for 4 menstrual cycles.
Calcium : 1200 mg of calcium to be taken for 4 menstrual cycles.
Placebo : For 5 cycles, women will receive placebo.
Overall Number of Participants Analyzed 13 13 13
Measure Type: Number
Unit of Measure: proportion of participants
0.77 0.31 0.31
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
8.Secondary Outcome
Title Proportion of Participants With PMTS LOCF Response to Treatment (50% Improvement)
Hide Description 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
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Hide Analysis Population Description
Response analysis includes all data from all subjects with the last observation carried forward to Visit 5.
Arm/Group Title I: Fluoxetine II: Calcium III: Placebo
Hide Arm/Group Description:
Fluoxetine : Fluoxetine 20 mg per day for 4 menstrual cycles.
Calcium : 1200 mg of calcium to be taken for 4 menstrual cycles.
Placebo : For 4 cycles, women will receive placebo.
Overall Number of Participants Analyzed 13 12 13
Measure Type: Number
Unit of Measure: proportion of participants
0.62 0.33 0.16
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.06
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
9.Secondary Outcome
Title Proportion of Participants With DRSP Visit-wise Response to Treatment (50% Improvement)
Hide Description 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
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Hide Analysis Population Description
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/Group Title I: Fluoxetine II: Calcium III: Placebo
Hide Arm/Group Description:
Fluoxetine : Fluoxetine 20 mg per day for 4 menstrual cycles.
Calcium : 1200 mg of calcium to be taken for 4 menstrual cycles.
Placebo : For 5 cycles, women will receive placebo.
Overall Number of Participants Analyzed 5 8 6
Measure Type: Number
Unit of Measure: proportion of participants
1.00 0.50 0.33
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.09
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
10.Secondary Outcome
Title Proportion of Patients With IDS Visit-wise Response to Treatment (50% Improvement)
Hide Description

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
For fluoxetine, calcium and placebo groups, 8, 11 and 12 participants remained in the trial until Visit 5.
Arm/Group Title I: Fluoxetine II: Calcium III: Placebo
Hide Arm/Group Description:
Fluoxetine : Fluoxetine 20 mg per day for 4 menstrual cycles.
Calcium : 1200 mg of calcium to be taken for 4 menstrual cycles.
Placebo : For 4 cycles, women will receive placebo.
Overall Number of Participants Analyzed 8 11 12
Measure Type: Number
Unit of Measure: proportion of participants
1.00 0.36 0.33
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
11.Secondary Outcome
Title Proportion of Patients With PMTS Visit-wise Response to Treatment (50% Improvement)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
For fluoxetine, calcium and placebo groups, 8, 11 and 12 participants remained in the trial until Visit 5.
Arm/Group Title I: Fluoxetine II: Calcium III: Placebo
Hide Arm/Group Description:
Fluoxetine : Fluoxetine 20 mg per day for 4 menstrual cycles.
Calcium : 1200 mg of calcium to be taken for 4 menstrual cycles.
Placebo : For 4 cycles, women will receive placebo.
Overall Number of Participants Analyzed 8 11 12
Measure Type: Number
Unit of Measure: proportion of participants
0.75 0.36 0.17
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection I: Fluoxetine, II: Calcium, III: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Time Frame From patient randomization to completion of study
Adverse Event Reporting Description Final adverse event data were only available for the 32 patients randomized at the Yale site. There were no severe adverse events by self-report. Events were uncommon and occurred in all 3 groups with a numerically higher number in the calcium group.
 
Arm/Group Title I: Fluoxetine II: Calcium III: Placebo
Hide Arm/Group Description Fluoxetine : Fluoxetine 20 mg per day for 4 menstrual cycles. Calcium : 1200 mg of calcium to be taken for 4 menstrual cycles. Placebo : For 4 cycles, women will receive placebo.
All-Cause Mortality
I: Fluoxetine II: Calcium III: Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
I: Fluoxetine II: Calcium III: Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      0/11 (0.00%)      0/11 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
I: Fluoxetine II: Calcium III: Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/10 (40.00%)      8/11 (72.73%)      2/11 (18.18%)    
Gastrointestinal disorders       
Abdominal ache   0/10 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Burping   0/10 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Constipation   1/10 (10.00%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Decreased appetite   0/10 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Diarrhea   1/10 (10.00%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Nausea   1/10 (10.00%)  1 4/11 (36.36%)  4 2/11 (18.18%)  2
General disorders       
Feeling spacy   0/10 (0.00%)  0 2/11 (18.18%)  2 0/11 (0.00%)  0
Difficulty Concentrating   0/10 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Dizziness   1/10 (10.00%)  1 2/11 (18.18%)  2 0/11 (0.00%)  0
Dry mouth   2/10 (20.00%)  2 0/11 (0.00%)  0 0/11 (0.00%)  0
Fatigue   0/10 (0.00%)  0 1/11 (9.09%)  1 1/11 (9.09%)  1
Headache   1/10 (10.00%)  1 3/11 (27.27%)  3 2/11 (18.18%)  2
Irritability   0/10 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Sweating   0/10 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Vertigo   0/10 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Reproductive system and breast disorders       
Cramps   1/10 (10.00%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Decreased sex drive   0/10 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Kimberly Yonkers
Organization: Donaghue Medical Research Foundation
Phone: 1-203-764-6621
Responsible Party: Kimberly Yonkers, Yale University
ClinicalTrials.gov Identifier: NCT00965562     History of Changes
Obsolete Identifiers: NCT00683605
Other Study ID Numbers: 0001011511
First Submitted: August 24, 2009
First Posted: August 25, 2009
Results First Submitted: July 2, 2013
Results First Posted: February 26, 2015
Last Update Posted: March 23, 2015