Premenstrual Dysphoric Disorder
Conditions
Keywords
Premenstrual Syndrome
Brief summary
This study will evaluate the effectiveness of sertraline in reducing symptoms in women diagnosed with premenstrual dysphoric disorder.
Detailed description
Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). PMDD affects nearly 5 percent of menstruating women in the United States. This disorder is very disruptive and can affect a woman's performance at work and her relationships with friends and family. Symptoms typically occur 10 to 14 days before the start of a woman's period and dissipate soon after. Sadness, rapid changes in mood, anxiety, and irritability are common symptoms associated with PMDD. Sertraline is a selective serotonin reuptake inhibitor (SSRI) that has been approved by the U.S. Food and Drug Administration (FDA) to treat PMDD. This study will evaluate the effectiveness of sertraline in reducing symptoms in women diagnosed with PMDD. All participants will begin this study by recording their symptoms for two complete menstrual cycles. At a baseline study visit, participants will then be randomly assigned to receive either sertraline or placebo for six menstrual cycles. At the onset of PMDD symptoms, participants will take two pills of their assigned treatment daily. Once symptoms have dissipated, usually around the first or second day of the menstrual cycle, participants will stop taking their assigned treatment for that cycle. For the next 4 months, participants will attend study visits on the fifth day of each monthly menstrual cycle. For the following 2 months, participants will be contacted by telephone. Participants will be asked to rate their mood and symptoms at each contact. A final study visit will be scheduled on the first day of the seventh menstrual cycle. At this point, all participants will be offered sertraline for an additional three menstrual cycles, dosed on a daily basis. Two study visits will be scheduled over the course of the three cycles to evaluate the effectiveness of sertraline when dosed continuously. Urine collection and pregnancy tests may occur at selected times during the study.
Interventions
DRUGSertraline
50 mg of sertraline will be taken at the onset of premenstrual symptoms through the first few days of menses. If a participant shows an insufficient response to this dose, the dose may be increased to 100 mg. Women who report moderate to severe side effects will be allowed to reduce their dose to 25 mg of sertraline and to increase the dose at the next cycle unless rate-limiting side effects continue.
DRUGPlacebo
50 mg of placebo will be taken at the onset of premenstrual symptoms through the first few days of menses. If a participant shows an insufficient response to this dose, the dose may be increased to 100 mg.
Sponsors
National Institute of Mental Health (NIMH)
Yale University
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
* Menstruating and has cycles between 21 and 35 days * Meets DSM-IV criteria for PMDD * Experienced symptoms of PMDD in at least 9 of 12 menstrual cycles within 1 year of study entry * Willing to use an effective form of birth control throughout the study
Exclusion criteria
* Meets MINI DSM-IV criteria for major depressive episode, substance abuse, bulimia nervosa, anorexia, bipolar disorder, or a psychotic disorder, such as schizophrenia or schizoaffective disorder, within 6 months of study entry * Meets MINI DSM-IV criteria for a substance dependence disorder within 12 months of study entry * Shows follicular phase symptoms consistent with a diagnosis of major depression * Shows symptoms consistent with bipolar disorder * Diagnosed with a severe, clinically significant co-existing condition that may prevent study participation * Suicidal * Taking ongoing antidepressant or other psychotropic medication * History of hypersensitivity or an adverse reaction to sertraline * Pregnant or breastfeeding * Currently undergoing treatment with a depot hormonal preparation or any other medication that would lead to a lack of menses or markedly irregular menses * Using a hormonal contraceptive pill or hormonal device within 6 months of study entry * Taking a hormonal contraceptive pill that includes 20 micrograms of ethinyl estradiol and 3 micrograms of drospirenone * Has been in individual psychotherapy or individual counseling for 3 months or less at study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DRSP | Baseline to Cycle 6 | DRSP (Daily Rating of Severity Problems) is composed of 21 items reflecting the 11 candidate symptoms for PMDD according to DSM IV and DSM V. Each symptom is scored 1-6. A diagnosis of PMDD requires a minimum average luteal phase score of greater than or equal to 3 (mild) for at least 5 PMDD symptoms during the five most symptomatic of the final seven luteal phase days and the first two days of menses onset, and we require that the average follicular phase score not be \>2 on these same items. The minimum score is 0 and maximum is 126 for the total score. A higher score indicates greater severity of symptoms. |
| Premenstrual Tension Scale (PMTS) | Measured from baseline to Cycle 6 | The PMTS is a 10-item scale constructed to study premenstrual syndromes. It is sensitive to change with treatment. It includes items of irritability-hostility, tension, efficiency, dysphoria, motor coordination, mental-cognitive functioning, eating habits, social impairment, sex drive, and physical symptoms. PMTS-O or PMTS-SR? Min=0 (asymptomatic), Max=40 (Highly symptomatic), higher scores indicate most severe problems |
| Inventory of Depression Symptoms (IDS-C) | Measured from baseline to Cycle 6 | Inventory of Depressive Symptomatology-Clinician version (IDS-C) - a depression measure that has 28 items and detects appropriate variations between follicular and luteal phases in subjects with PMDD. Min score is 0, max is 84.Lower score is less symptomatic. |
| Michelson SSRI Withdrawal Checklist | Measured from Cycle 1 to Cycle 6 | Michelson SSRI Withdrawal Checklist - 16-item (not exactly 17-item, mood swings and crying were in DRSP) including dizziness, nausea, unusual dreams, chills, increased sweating, loose stools, agitation, ringing or noises in the ears. Items were summed for 3 days after pill-taking ended for each menstrual cycle.Scale is 0-80 for total range of the scale with lower less severe. There are no units |
| Number of Days Pills Were Taken | Measured from Cycle 1 to Cycle 6 | The number of days that pills were taken on. |
| Number of Symptomatic Days Before Pills Were Taken | Cycle 1 to Cycle 6 | Symptomatic days were those that participant experienced at least 3 symptoms at a severity of at least 3, which is a mean of at least mild. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Severity (CGI-S) | Baseline through Cycle 6 | Clinical Global Impressions-Severity is measured on a scale of 1-7, with 7 as most severe. |
| DRSP Depression Subscale | Baseline to Cycle 6 | Depressive symptoms included: felt depressed, felt hopeless, felt worthless or guilt, slept more, trouble sleeping, felt overwhelmed. Symptoms were scored on a scale of 1-6 The score range is 0-36 with higher indicating greater severity. |
| DRSP Physical Subscale | Baseline to Cycle 6 | Physical symptoms included breast tenderness, bloating, headache, joint or muscle pain. Symptoms were scored on a scale of 1-6. The severity range is 0-24 with 24 being more symptomatic. |
| DRSP Anger/Irritability Subscale | Baseline to Cycle 6 | Anger/irritability included anger/irritability and conflicts with people. Symptoms were scored on a scale 1-6. The range is 0 to 12 with a higher score indicating greater symptom severity. |
| Clinical Global Impressions-Improvement (CGI-I) | Cycle 1 to Cycle 6 | The Clinical Global Impressions-Improvement (CGI-I) scale is a 7-point scale with 7 being the least improvement. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Baseline through Cycle 6 | A measurement of frequency of adverse events by random assignment |
Countries
United States
Participant flow
Recruitment details
Three-center study; New Haven, CT; New York City, NY; Richmond, VA. Participants recruited via direct mail and advertisements. Assessed initially over phone, then face-to-face screening office visit. Screening took place between September 2007 and February 2012.
Participants by arm
| Arm | Count |
|---|---|
| Sertraline Participants will take sertraline that is dosed between 50 and 100 mgs during the symptomatic period
Sertraline: 50 mg of sertraline will be taken at the onset of premenstrual symptoms through the first few days of menses. If a participant shows an insufficient response to this dose, the dose may be increased to 100 mg. Women who report moderate to severe side effects will be allowed to reduce their dose to 25 mg of sertraline and to increase the dose at the next cycle unless rate-limiting side effects continue. | 125 |
| Placebo Participants will take similarly looking placebo during the symptomatic period
Placebo: 50 mg of placebo will be taken at the onset of premenstrual symptoms through the first few days of menses. If a participant shows an insufficient response to this dose, the dose may be increased to 100 mg. | 127 |
| Total | 252 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Lost to Follow-up | 15 | 14 |
| Overall Study | Pregnancy | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Rescue | 3 | 9 |
| Overall Study | Withdrawal by Subject | 16 | 12 |
Baseline characteristics
| Characteristic | Sertraline | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 33.7 years STANDARD_DEVIATION 6.71 | 34.6 years STANDARD_DEVIATION 6.9 | 34.17 years STANDARD_DEVIATION 6.82 |
| Baseline Length of Menstrual Cycle | 27.92 days STANDARD_DEVIATION 5.26 | 27.02 days STANDARD_DEVIATION 4.58 | 27.4 days STANDARD_DEVIATION 4.9 |
| Baseline Luteal Phase Daily Rating of Severity of Problems Score | 61.20 units on a scale STANDARD_DEVIATION 20.09 | 60.37 units on a scale STANDARD_DEVIATION 17.37 | 60.8 units on a scale STANDARD_DEVIATION 18.7 |
| Education College/graduate or professional school | 73 participants | 94 participants | 167 participants |
| Education Missing | 1 participants | 0 participants | 1 participants |
| Education Some college | 40 participants | 22 participants | 62 participants |
| Education Some high school/high school graduate | 11 participants | 11 participants | 22 participants |
| Marital status Divorced/separated | 11 participants | 14 participants | 25 participants |
| Marital status Living with partner | 14 participants | 20 participants | 34 participants |
| Marital status Married | 51 participants | 42 participants | 93 participants |
| Marital status Never married | 49 participants | 51 participants | 100 participants |
| Past Psychiatric Conditions: Major Depressive Disorder No | 90 participants | 84 participants | 174 participants |
| Past Psychiatric Conditions: Major Depressive Disorder Yes | 35 participants | 43 participants | 78 participants |
| Race/Ethnicity, Customized Asian/mixed/other | 5 participants | 5 participants | 10 participants |
| Race/Ethnicity, Customized Black | 19 participants | 20 participants | 39 participants |
| Race/Ethnicity, Customized Hispanic | 15 participants | 13 participants | 28 participants |
| Race/Ethnicity, Customized White | 86 participants | 89 participants | 175 participants |
| Region of Enrollment United States | 125 participants | 127 participants | 252 participants |
| Sex: Female, Male Female | 125 Participants | 127 Participants | 252 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 48 / 125 | 40 / 127 |
| serious Total, serious adverse events | 0 / 125 | 0 / 127 |
Outcome results
Primary
DRSP
DRSP (Daily Rating of Severity Problems) is composed of 21 items reflecting the 11 candidate symptoms for PMDD according to DSM IV and DSM V. Each symptom is scored 1-6. A diagnosis of PMDD requires a minimum average luteal phase score of greater than or equal to 3 (mild) for at least 5 PMDD symptoms during the five most symptomatic of the final seven luteal phase days and the first two days of menses onset, and we require that the average follicular phase score not be \>2 on these same items. The minimum score is 0 and maximum is 126 for the total score. A higher score indicates greater severity of symptoms.
Time frame: Baseline to Cycle 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sertraline | DRSP | Baseline | 60.3 units on a scale | Standard Deviation 19.5 |
| Sertraline | DRSP | Cycle 1 | 43.7 units on a scale | Standard Deviation 17.4 |
| Sertraline | DRSP | Cycle 2 | 38.7 units on a scale | Standard Deviation 15.8 |
| Sertraline | DRSP | Cycle 3 | 36.8 units on a scale | Standard Deviation 15.7 |
| Sertraline | DRSP | Cycle 4 | 35.3 units on a scale | Standard Deviation 12.2 |
| Sertraline | DRSP | Cycle 5 | 31.7 units on a scale | Standard Deviation 10.5 |
| Sertraline | DRSP | Cycle 6 | 32.2 units on a scale | Standard Deviation 10.4 |
| Sertraline | DRSP | Average change from baseline | -29.7 units on a scale | Standard Deviation 18.8 |
| Placebo | DRSP | Average change from baseline | -22.4 units on a scale | Standard Deviation 16 |
| Placebo | DRSP | Baseline | 59.5 units on a scale | Standard Deviation 17.3 |
| Placebo | DRSP | Cycle 4 | 36.9 units on a scale | Standard Deviation 11.3 |
| Placebo | DRSP | Cycle 1 | 46.1 units on a scale | Standard Deviation 17.2 |
| Placebo | DRSP | Cycle 6 | 36.1 units on a scale | Standard Deviation 13.6 |
| Placebo | DRSP | Cycle 2 | 44.4 units on a scale | Standard Deviation 17.5 |
| Placebo | DRSP | Cycle 5 | 35.2 units on a scale | Standard Deviation 12.7 |
| Placebo | DRSP | Cycle 3 | 40.7 units on a scale | Standard Deviation 14.7 |
Comparison: Group comparisonp-value: 0.83ANOVA
Comparison: Change over time in both groupsp-value: <0.001ANOVA
Comparison: Group by time: comparison rates of changep-value: 0.02ANOVA
Comparison: Estimated mean difference from baseline to end point between active vs. placebop-value: 0.16995% CI: [0.96, 1.25]Mixed Models Analysis
Primary
Inventory of Depression Symptoms (IDS-C)
Inventory of Depressive Symptomatology-Clinician version (IDS-C) - a depression measure that has 28 items and detects appropriate variations between follicular and luteal phases in subjects with PMDD. Min score is 0, max is 84.Lower score is less symptomatic.
Time frame: Measured from baseline to Cycle 6
Population: all participants enrolled were analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sertraline | Inventory of Depression Symptoms (IDS-C) | Cycle 4 | 17.3 units on a scale | Standard Deviation 11.1 |
| Sertraline | Inventory of Depression Symptoms (IDS-C) | Cycle 2 | 21.0 units on a scale | Standard Deviation 11.7 |
| Sertraline | Inventory of Depression Symptoms (IDS-C) | Cycle 5 | 15.2 units on a scale | Standard Deviation 9.9 |
| Sertraline | Inventory of Depression Symptoms (IDS-C) | Cycle 1 | 23.7 units on a scale | Standard Deviation 12.3 |
| Sertraline | Inventory of Depression Symptoms (IDS-C) | Cycle 6 | 15.5 units on a scale | Standard Deviation 10.7 |
| Sertraline | Inventory of Depression Symptoms (IDS-C) | Cycle 3 | 19.2 units on a scale | Standard Deviation 13.1 |
| Sertraline | Inventory of Depression Symptoms (IDS-C) | Average change from baseline | -20.0 units on a scale | Standard Deviation 11.4 |
| Sertraline | Inventory of Depression Symptoms (IDS-C) | Baseline | 35.4 units on a scale | Standard Deviation 10.7 |
| Placebo | Inventory of Depression Symptoms (IDS-C) | Average change from baseline | -15.3 units on a scale | Standard Deviation 12.5 |
| Placebo | Inventory of Depression Symptoms (IDS-C) | Cycle 1 | 24.0 units on a scale | Standard Deviation 11.4 |
| Placebo | Inventory of Depression Symptoms (IDS-C) | Cycle 2 | 22.8 units on a scale | Standard Deviation 10.6 |
| Placebo | Inventory of Depression Symptoms (IDS-C) | Cycle 3 | 19.6 units on a scale | Standard Deviation 10 |
| Placebo | Inventory of Depression Symptoms (IDS-C) | Cycle 4 | 19.1 units on a scale | Standard Deviation 9.9 |
| Placebo | Inventory of Depression Symptoms (IDS-C) | Cycle 5 | 16.7 units on a scale | Standard Deviation 10.4 |
| Placebo | Inventory of Depression Symptoms (IDS-C) | Cycle 6 | 17.8 units on a scale | Standard Deviation 11 |
| Placebo | Inventory of Depression Symptoms (IDS-C) | Baseline | 32.8 units on a scale | Standard Deviation 10.4 |
Comparison: Group comparisonp-value: 0.54ANOVA
Comparison: Change over time in both groupsp-value: <0.001ANOVA
Comparison: Group by time: comparison of rates of changep-value: 0.02ANOVA
Comparison: Estimated mean difference from baseline to end point between active vs. placebop-value: 0.001595% CI: [1.97, 8.31]Mixed Models Analysis
Primary
Michelson SSRI Withdrawal Checklist
Michelson SSRI Withdrawal Checklist - 16-item (not exactly 17-item, mood swings and crying were in DRSP) including dizziness, nausea, unusual dreams, chills, increased sweating, loose stools, agitation, ringing or noises in the ears. Items were summed for 3 days after pill-taking ended for each menstrual cycle.Scale is 0-80 for total range of the scale with lower less severe. There are no units
Time frame: Measured from Cycle 1 to Cycle 6
Population: all participants enrolled were analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sertraline | Michelson SSRI Withdrawal Checklist | Cycle 1 | 72.9 units on a scale | Standard Deviation 29.3 |
| Sertraline | Michelson SSRI Withdrawal Checklist | Cycle 2 | 73.4 units on a scale | Standard Deviation 29.9 |
| Sertraline | Michelson SSRI Withdrawal Checklist | Cycle 3 | 70.3 units on a scale | Standard Deviation 27.9 |
| Sertraline | Michelson SSRI Withdrawal Checklist | Cycle 4 | 62.3 units on a scale | Standard Deviation 25.1 |
| Sertraline | Michelson SSRI Withdrawal Checklist | Cycle 5 | 63.9 units on a scale | Standard Deviation 19.9 |
| Sertraline | Michelson SSRI Withdrawal Checklist | Cycle 6 | 67.5 units on a scale | Standard Deviation 22.1 |
| Placebo | Michelson SSRI Withdrawal Checklist | Cycle 5 | 62.1 units on a scale | Standard Deviation 24 |
| Placebo | Michelson SSRI Withdrawal Checklist | Cycle 1 | 68.1 units on a scale | Standard Deviation 25.4 |
| Placebo | Michelson SSRI Withdrawal Checklist | Cycle 4 | 65.4 units on a scale | Standard Deviation 25.3 |
| Placebo | Michelson SSRI Withdrawal Checklist | Cycle 2 | 75.2 units on a scale | Standard Deviation 33.1 |
| Placebo | Michelson SSRI Withdrawal Checklist | Cycle 6 | 76.2 units on a scale | Standard Deviation 34.1 |
| Placebo | Michelson SSRI Withdrawal Checklist | Cycle 3 | 71.7 units on a scale | Standard Deviation 39 |
Comparison: Group comparisonp-value: 0.46ANOVA
Comparison: Change over time in both groupsp-value: <0.0001ANOVA
Comparison: Group by time: comparison rates of changep-value: 0.69ANOVA
Comparison: Estimated mean difference from Cycle 1 to end point between active vs. placebop-value: 0.8495% CI: [0.83, 1.26]Mixed Models Analysis
Primary
Number of Days Pills Were Taken
The number of days that pills were taken on.
Time frame: Measured from Cycle 1 to Cycle 6
Population: all participants enrolled were analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sertraline | Number of Days Pills Were Taken | Cycle 6 | 6.9 number of days | Standard Deviation 3.8 |
| Sertraline | Number of Days Pills Were Taken | Cycle 4 | 7.0 number of days | Standard Deviation 3.8 |
| Sertraline | Number of Days Pills Were Taken | Cycle 2 | 7.4 number of days | Standard Deviation 3.3 |
| Sertraline | Number of Days Pills Were Taken | Cycle 5 | 7.6 number of days | Standard Deviation 4 |
| Sertraline | Number of Days Pills Were Taken | Cycle 1 | 6.5 number of days | Standard Deviation 3.4 |
| Sertraline | Number of Days Pills Were Taken | Average Change from Cycle 1 | 0.3 number of days | Standard Deviation 4.2 |
| Sertraline | Number of Days Pills Were Taken | Cycle 3 | 8.2 number of days | Standard Deviation 3.7 |
| Placebo | Number of Days Pills Were Taken | Average Change from Cycle 1 | -0.3 number of days | Standard Deviation 3.6 |
| Placebo | Number of Days Pills Were Taken | Cycle 1 | 6.6 number of days | Standard Deviation 3.4 |
| Placebo | Number of Days Pills Were Taken | Cycle 2 | 6.7 number of days | Standard Deviation 3.3 |
| Placebo | Number of Days Pills Were Taken | Cycle 3 | 7.1 number of days | Standard Deviation 3.4 |
| Placebo | Number of Days Pills Were Taken | Cycle 4 | 6.9 number of days | Standard Deviation 3.4 |
| Placebo | Number of Days Pills Were Taken | Cycle 6 | 6.1 number of days | Standard Deviation 3.7 |
| Placebo | Number of Days Pills Were Taken | Cycle 5 | 6.7 number of days | Standard Deviation 3.4 |
Comparison: Group comparisonp-value: 0.3ANOVA
Comparison: Change over time in both groupsp-value: <0.01ANOVA
Comparison: Group by time: comparison rates of changep-value: 0.73ANOVA
Comparison: Estimated mean difference from baseline to end point between active vs. placebop-value: 0.0695% CI: [0.92, 1.35]Mixed Models Analysis
Primary
Number of Symptomatic Days Before Pills Were Taken
Symptomatic days were those that participant experienced at least 3 symptoms at a severity of at least 3, which is a mean of at least mild.
Time frame: Cycle 1 to Cycle 6
Population: all enrolled participants were analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sertraline | Number of Symptomatic Days Before Pills Were Taken | Cycle 3 | 1.9 days | Standard Deviation 2.8 |
| Sertraline | Number of Symptomatic Days Before Pills Were Taken | Cycle 5 | 1.9 days | Standard Deviation 2.9 |
| Sertraline | Number of Symptomatic Days Before Pills Were Taken | Cycle 2 | 2.0 days | Standard Deviation 2.2 |
| Sertraline | Number of Symptomatic Days Before Pills Were Taken | Cycle 6 | 1.7 days | Standard Deviation 2.3 |
| Sertraline | Number of Symptomatic Days Before Pills Were Taken | Cycle 4 | 2.0 days | Standard Deviation 2.7 |
| Sertraline | Number of Symptomatic Days Before Pills Were Taken | Average Change from Cycle 1 | -0.7 days | Standard Deviation 3.4 |
| Sertraline | Number of Symptomatic Days Before Pills Were Taken | Cycle 1 | 2.8 days | Standard Deviation 3 |
| Placebo | Number of Symptomatic Days Before Pills Were Taken | Average Change from Cycle 1 | -1.0 days | Standard Deviation 3.2 |
| Placebo | Number of Symptomatic Days Before Pills Were Taken | Cycle 1 | 2.6 days | Standard Deviation 3 |
| Placebo | Number of Symptomatic Days Before Pills Were Taken | Cycle 2 | 2.7 days | Standard Deviation 3.1 |
| Placebo | Number of Symptomatic Days Before Pills Were Taken | Cycle 3 | 2.0 days | Standard Deviation 2.7 |
| Placebo | Number of Symptomatic Days Before Pills Were Taken | Cycle 4 | 2.0 days | Standard Deviation 2.9 |
| Placebo | Number of Symptomatic Days Before Pills Were Taken | Cycle 5 | 1.8 days | Standard Deviation 2.4 |
| Placebo | Number of Symptomatic Days Before Pills Were Taken | Cycle 6 | 2.0 days | Standard Deviation 3.2 |
Comparison: Group comparisonp-value: 0.8ANOVA
Comparison: Change over time in both groupsp-value: <0.001ANOVA
Comparison: Group by time: comparison rates of changep-value: 0.43ANOVA
Comparison: Estimated mean difference from baseline to endpoint between active vs. placebop-value: 0.6195% CI: [0.85, 1.45]Mixed Models Analysis
Primary
Premenstrual Tension Scale (PMTS)
The PMTS is a 10-item scale constructed to study premenstrual syndromes. It is sensitive to change with treatment. It includes items of irritability-hostility, tension, efficiency, dysphoria, motor coordination, mental-cognitive functioning, eating habits, social impairment, sex drive, and physical symptoms. PMTS-O or PMTS-SR? Min=0 (asymptomatic), Max=40 (Highly symptomatic), higher scores indicate most severe problems
Time frame: Measured from baseline to Cycle 6
Population: all randomized participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sertraline | Premenstrual Tension Scale (PMTS) | Cycle 4 | 12.9 units on a scale | Standard Deviation 6.7 |
| Sertraline | Premenstrual Tension Scale (PMTS) | Cycle 1 | 15.6 units on a scale | Standard Deviation 7.3 |
| Sertraline | Premenstrual Tension Scale (PMTS) | Cycle 5 | 11.4 units on a scale | Standard Deviation 6.3 |
| Sertraline | Premenstrual Tension Scale (PMTS) | Baseline | 22.3 units on a scale | Standard Deviation 4.8 |
| Sertraline | Premenstrual Tension Scale (PMTS) | Cycle 6 | 11.7 units on a scale | Standard Deviation 6.8 |
| Sertraline | Premenstrual Tension Scale (PMTS) | Cycle 3 | 13.0 units on a scale | Standard Deviation 8 |
| Sertraline | Premenstrual Tension Scale (PMTS) | Average change from baseline | -10.6 units on a scale | Standard Deviation 6.6 |
| Sertraline | Premenstrual Tension Scale (PMTS) | Cycle 2 | 14.1 units on a scale | Standard Deviation 6.9 |
| Placebo | Premenstrual Tension Scale (PMTS) | Average change from baseline | -8.9 units on a scale | Standard Deviation 7.4 |
| Placebo | Premenstrual Tension Scale (PMTS) | Baseline | 21.4 units on a scale | Standard Deviation 4.5 |
| Placebo | Premenstrual Tension Scale (PMTS) | Cycle 2 | 15.6 units on a scale | Standard Deviation 6.1 |
| Placebo | Premenstrual Tension Scale (PMTS) | Cycle 3 | 14.0 units on a scale | Standard Deviation 5.8 |
| Placebo | Premenstrual Tension Scale (PMTS) | Cycle 4 | 13.9 units on a scale | Standard Deviation 6.3 |
| Placebo | Premenstrual Tension Scale (PMTS) | Cycle 5 | 12.4 units on a scale | Standard Deviation 6.3 |
| Placebo | Premenstrual Tension Scale (PMTS) | Cycle 6 | 12.8 units on a scale | Standard Deviation 6.9 |
| Placebo | Premenstrual Tension Scale (PMTS) | Cycle 1 | 16.8 units on a scale | Standard Deviation 6 |
Comparison: Group comparisonp-value: 0.21ANOVA
Comparison: Change over time in both groupsp-value: <0.001ANOVA
Comparison: Group by time: comparison of rates of changep-value: 0.06ANOVA
Comparison: Estimated mean difference from baseline to endpoint between active vs. placebop-value: 0.04995% CI: [0.01, 3.75]Mixed Models Analysis
Secondary
Clinical Global Impressions-Improvement (CGI-I)
The Clinical Global Impressions-Improvement (CGI-I) scale is a 7-point scale with 7 being the least improvement.
Time frame: Cycle 1 to Cycle 6
Population: all participants who were measured at a visit past baseline were analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sertraline | Clinical Global Impressions-Improvement (CGI-I) | Cycle 6 | 1.8 units on a scale | Standard Deviation 0.9 |
| Sertraline | Clinical Global Impressions-Improvement (CGI-I) | Cycle 1 | 2.7 units on a scale | Standard Deviation 1.1 |
| Sertraline | Clinical Global Impressions-Improvement (CGI-I) | Cycle 2 | 2.4 units on a scale | Standard Deviation 1 |
| Sertraline | Clinical Global Impressions-Improvement (CGI-I) | Cycle 3 | 2.3 units on a scale | Standard Deviation 1.3 |
| Sertraline | Clinical Global Impressions-Improvement (CGI-I) | Cycle 4 | 2.1 units on a scale | Standard Deviation 1.2 |
| Sertraline | Clinical Global Impressions-Improvement (CGI-I) | Cycle 5 | 2.0 units on a scale | Standard Deviation 1 |
| Sertraline | Clinical Global Impressions-Improvement (CGI-I) | Average change from Cycle 1 | -0.9 units on a scale | Standard Deviation 1.2 |
| Placebo | Clinical Global Impressions-Improvement (CGI-I) | Cycle 6 | 2.2 units on a scale | Standard Deviation 1.3 |
| Placebo | Clinical Global Impressions-Improvement (CGI-I) | Cycle 4 | 2.5 units on a scale | Standard Deviation 1.3 |
| Placebo | Clinical Global Impressions-Improvement (CGI-I) | Cycle 1 | 3.2 units on a scale | Standard Deviation 1 |
| Placebo | Clinical Global Impressions-Improvement (CGI-I) | Average change from Cycle 1 | -0.8 units on a scale | Standard Deviation 1.4 |
| Placebo | Clinical Global Impressions-Improvement (CGI-I) | Cycle 2 | 2.7 units on a scale | Standard Deviation 1.1 |
| Placebo | Clinical Global Impressions-Improvement (CGI-I) | Cycle 5 | 2.1 units on a scale | Standard Deviation 1.2 |
| Placebo | Clinical Global Impressions-Improvement (CGI-I) | Cycle 3 | 2.4 units on a scale | Standard Deviation 1 |
Comparison: Group comparisonp-value: 0.01Chi-squared
Comparison: Group by time: comparison rates of changep-value: <0.001Chi-squared
Comparison: Estimated mean difference between active and placebo groups at end-point onlyp-value: 0.05695% CI: [0.3, 1.02]Mixed Models Analysis
Secondary
Clinical Global Severity (CGI-S)
Clinical Global Impressions-Severity is measured on a scale of 1-7, with 7 as most severe.
Time frame: Baseline through Cycle 6
Population: all participants enrolled analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sertraline | Clinical Global Severity (CGI-S) | Cycle 3 | 2.8 units on a scale | Standard Deviation 1.3 |
| Sertraline | Clinical Global Severity (CGI-S) | Cycle 6 | 2.2 units on a scale | Standard Deviation 1.1 |
| Sertraline | Clinical Global Severity (CGI-S) | Baseline | 4.5 units on a scale | Standard Deviation 0.7 |
| Sertraline | Clinical Global Severity (CGI-S) | Cycle 4 | 2.6 units on a scale | Standard Deviation 1.2 |
| Sertraline | Clinical Global Severity (CGI-S) | Cycle 2 | 3.1 units on a scale | Standard Deviation 1.2 |
| Sertraline | Clinical Global Severity (CGI-S) | Cycle 5 | 2.4 units on a scale | Standard Deviation 1 |
| Sertraline | Clinical Global Severity (CGI-S) | Average change from baseline | -2.3 units on a scale | Standard Deviation 1.2 |
| Sertraline | Clinical Global Severity (CGI-S) | Cycle 1 | 3.4 units on a scale | Standard Deviation 1 |
| Placebo | Clinical Global Severity (CGI-S) | Average change from baseline | -1.9 units on a scale | Standard Deviation 1.4 |
| Placebo | Clinical Global Severity (CGI-S) | Baseline | 4.5 units on a scale | Standard Deviation 0.6 |
| Placebo | Clinical Global Severity (CGI-S) | Cycle 1 | 3.8 units on a scale | Standard Deviation 0.9 |
| Placebo | Clinical Global Severity (CGI-S) | Cycle 2 | 3.3 units on a scale | Standard Deviation 1.1 |
| Placebo | Clinical Global Severity (CGI-S) | Cycle 3 | 3.0 units on a scale | Standard Deviation 1 |
| Placebo | Clinical Global Severity (CGI-S) | Cycle 6 | 2.5 units on a scale | Standard Deviation 1.3 |
| Placebo | Clinical Global Severity (CGI-S) | Cycle 4 | 2.9 units on a scale | Standard Deviation 1.2 |
| Placebo | Clinical Global Severity (CGI-S) | Cycle 5 | 2.7 units on a scale | Standard Deviation 1.1 |
Comparison: Group comparisonp-value: 0.01Chi-squared
Comparison: Change over time in both groupsp-value: <0.001Chi-squared
Comparison: Group by time: comparison rates of changep-value: 0.28Chi-squared
Comparison: Estimated mean difference from baseline to end point between active vs. placebop-value: 0.05695% CI: [0.3, 1.19]Mixed Models Analysis
Secondary
DRSP Anger/Irritability Subscale
Anger/irritability included anger/irritability and conflicts with people. Symptoms were scored on a scale 1-6. The range is 0 to 12 with a higher score indicating greater symptom severity.
Time frame: Baseline to Cycle 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sertraline | DRSP Anger/Irritability Subscale | Baseline | 6.4 units on a scale | Standard Deviation 2.2 |
| Sertraline | DRSP Anger/Irritability Subscale | Cycle 1 | 4.1 units on a scale | Standard Deviation 1.9 |
| Sertraline | DRSP Anger/Irritability Subscale | Cycle 2 | 3.5 units on a scale | Standard Deviation 1.7 |
| Sertraline | DRSP Anger/Irritability Subscale | Cycle 3 | 3.3 units on a scale | Standard Deviation 1.7 |
| Sertraline | DRSP Anger/Irritability Subscale | Cycle 4 | 3.2 units on a scale | Standard Deviation 1.4 |
| Sertraline | DRSP Anger/Irritability Subscale | Cycle 5 | 2.9 units on a scale | Standard Deviation 1.3 |
| Sertraline | DRSP Anger/Irritability Subscale | Cycle 6 | 2.8 units on a scale | Standard Deviation 1.4 |
| Sertraline | DRSP Anger/Irritability Subscale | Average change from baseline | -3.7 units on a scale | Standard Deviation 2.2 |
| Placebo | DRSP Anger/Irritability Subscale | Average change from baseline | -2.8 units on a scale | Standard Deviation 1.9 |
| Placebo | DRSP Anger/Irritability Subscale | Baseline | 6.3 units on a scale | Standard Deviation 2.1 |
| Placebo | DRSP Anger/Irritability Subscale | Cycle 4 | 3.8 units on a scale | Standard Deviation 1.6 |
| Placebo | DRSP Anger/Irritability Subscale | Cycle 1 | 4.6 units on a scale | Standard Deviation 2.1 |
| Placebo | DRSP Anger/Irritability Subscale | Cycle 6 | 3.5 units on a scale | Standard Deviation 1.5 |
| Placebo | DRSP Anger/Irritability Subscale | Cycle 2 | 4.5 units on a scale | Standard Deviation 2.3 |
| Placebo | DRSP Anger/Irritability Subscale | Cycle 5 | 3.5 units on a scale | Standard Deviation 1.7 |
| Placebo | DRSP Anger/Irritability Subscale | Cycle 3 | 4.0 units on a scale | Standard Deviation 1.9 |
Comparison: Group comparisonp-value: <0.001ANOVA
Comparison: Change over time in both groupsp-value: <0.001ANOVA
Comparison: Group by time: comparison rates of changep-value: <0.01ANOVA
Comparison: Estimated mean difference from baseline to end point between active vs. placebop-value: 0.02795% CI: [1.05, 1.41]Mixed Models Analysis
Secondary
DRSP Depression Subscale
Depressive symptoms included: felt depressed, felt hopeless, felt worthless or guilt, slept more, trouble sleeping, felt overwhelmed. Symptoms were scored on a scale of 1-6 The score range is 0-36 with higher indicating greater severity.
Time frame: Baseline to Cycle 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sertraline | DRSP Depression Subscale | Average change from baseline | -4.0 units on a scale | Standard Deviation 4 |
| Sertraline | DRSP Depression Subscale | Cycle 3 | 4.6 units on a scale | Standard Deviation 2.7 |
| Sertraline | DRSP Depression Subscale | Cycle 1 | 5.5 units on a scale | Standard Deviation 3 |
| Sertraline | DRSP Depression Subscale | Cycle 4 | 4.3 units on a scale | Standard Deviation 1.9 |
| Sertraline | DRSP Depression Subscale | Baseline | 7.5 units on a scale | Standard Deviation 4 |
| Sertraline | DRSP Depression Subscale | Cycle 5 | 3.9 units on a scale | Standard Deviation 1.6 |
| Sertraline | DRSP Depression Subscale | Cycle 2 | 4.8 units on a scale | Standard Deviation 2.7 |
| Sertraline | DRSP Depression Subscale | Cycle 6 | 3.9 units on a scale | Standard Deviation 2 |
| Placebo | DRSP Depression Subscale | Cycle 2 | 4.9 units on a scale | Standard Deviation 2.4 |
| Placebo | DRSP Depression Subscale | Average change from baseline | -2.7 units on a scale | Standard Deviation 3 |
| Placebo | DRSP Depression Subscale | Baseline | 7.2 units on a scale | Standard Deviation 3.5 |
| Placebo | DRSP Depression Subscale | Cycle 1 | 5.7 units on a scale | Standard Deviation 8.4 |
| Placebo | DRSP Depression Subscale | Cycle 6 | 4.2 units on a scale | Standard Deviation 2 |
| Placebo | DRSP Depression Subscale | Cycle 3 | 4.6 units on a scale | Standard Deviation 2 |
| Placebo | DRSP Depression Subscale | Cycle 4 | 4.3 units on a scale | Standard Deviation 1.5 |
| Placebo | DRSP Depression Subscale | Cycle 5 | 4.2 units on a scale | Standard Deviation 1.8 |
Comparison: Group comparisonp-value: 0.37ANOVA
Comparison: Change over time in both groupsp-value: <0.001ANOVA
Comparison: Group by time: comparison rates of changep-value: 0.73ANOVA
Comparison: Estimated mean difference from baseline to end point between active vs. placebop-value: 0.1395% CI: [0.91, 1.28]Mixed Models Analysis
Secondary
DRSP Physical Subscale
Physical symptoms included breast tenderness, bloating, headache, joint or muscle pain. Symptoms were scored on a scale of 1-6. The severity range is 0-24 with 24 being more symptomatic.
Time frame: Baseline to Cycle 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sertraline | DRSP Physical Subscale | Baseline | 10.6 units on a scale | Standard Deviation 3.6 |
| Sertraline | DRSP Physical Subscale | Cycle 1 | 8.4 units on a scale | Standard Deviation 3.5 |
| Sertraline | DRSP Physical Subscale | Cycle 2 | 8.2 units on a scale | Standard Deviation 3.7 |
| Sertraline | DRSP Physical Subscale | Cycle 3 | 7.8 units on a scale | Standard Deviation 3.2 |
| Sertraline | DRSP Physical Subscale | Cycle 4 | 7.4 units on a scale | Standard Deviation 3.2 |
| Sertraline | DRSP Physical Subscale | Cycle 5 | 6.9 units on a scale | Standard Deviation 2.7 |
| Sertraline | DRSP Physical Subscale | Cycle 6 | 6.9 units on a scale | Standard Deviation 2.6 |
| Sertraline | DRSP Physical Subscale | Average change from baseline | -4.2 units on a scale | Standard Deviation 3.8 |
| Placebo | DRSP Physical Subscale | Average change from baseline | -2.9 units on a scale | Standard Deviation 3.5 |
| Placebo | DRSP Physical Subscale | Baseline | 10.6 units on a scale | Standard Deviation 3.9 |
| Placebo | DRSP Physical Subscale | Cycle 4 | 7.3 units on a scale | Standard Deviation 2.8 |
| Placebo | DRSP Physical Subscale | Cycle 1 | 8.4 units on a scale | Standard Deviation 3.6 |
| Placebo | DRSP Physical Subscale | Cycle 6 | 7.4 units on a scale | Standard Deviation 2.9 |
| Placebo | DRSP Physical Subscale | Cycle 2 | 8.8 units on a scale | Standard Deviation 3.8 |
| Placebo | DRSP Physical Subscale | Cycle 5 | 7.1 units on a scale | Standard Deviation 3 |
| Placebo | DRSP Physical Subscale | Cycle 3 | 8.1 units on a scale | Standard Deviation 3.4 |
Comparison: Group comparisonp-value: 0.31ANOVA
Comparison: Change over time in both groupsp-value: <0.001ANOVA
Comparison: Group by time: comparison rates of changep-value: 0.46ANOVA
Comparison: Estimated mean difference from baseline to end point between active vs. placebop-value: 0.9495% CI: [0.96, 1.23]Mixed Models Analysis
Other Pre-specified
Adverse Events
A measurement of frequency of adverse events by random assignment
Time frame: Baseline through Cycle 6
Population: all enrolled participants were analyzed
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sertraline | Adverse Events | Mouth dryness | 5 participants |
| Sertraline | Adverse Events | Headache | 19 participants |
| Sertraline | Adverse Events | Difficulty concentrating | 9 participants |
| Sertraline | Adverse Events | Diarrhea | 14 participants |
| Sertraline | Adverse Events | Anxiety, agitation | 6 participants |
| Sertraline | Adverse Events | Insomnia | 9 participants |
| Sertraline | Adverse Events | Diaphoresis | 10 participants |
| Sertraline | Adverse Events | Nausea | 15 participants |
| Sertraline | Adverse Events | Dizziness/lightheadedness | 6 participants |
| Sertraline | Adverse Events | Fatigue | 14 participants |
| Placebo | Adverse Events | Dizziness/lightheadedness | 9 participants |
| Placebo | Adverse Events | Nausea | 35 participants |
| Placebo | Adverse Events | Diarrhea | 22 participants |
| Placebo | Adverse Events | Headache | 14 participants |
| Placebo | Adverse Events | Insomnia | 22 participants |
| Placebo | Adverse Events | Mouth dryness | 13 participants |
| Placebo | Adverse Events | Difficulty concentrating | 8 participants |
| Placebo | Adverse Events | Anxiety, agitation | 10 participants |
| Placebo | Adverse Events | Diaphoresis | 6 participants |
| Placebo | Adverse Events | Fatigue | 15 participants |