Official Title: “A Placebo-Controlled Study to Investigate the Onset of Action of Paroxetine When Used for the Treatment of Premenstrual Dysphoria”

The objective of this study is to explore the onset of action when serotonin reuptake inhibitors are used to treat premenstrual dysphoric disorder

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Whereas serotonin reuptake inhibitors (SRIs) usually require weeks of treatment to effectively counteract depressed mood or anxiety, several studies suggest that they may reduce the symptoms irritability and anger more rapidly. In line with this, SRIs have been shown to reduce certain symptoms, including irritability, in women with premenstrual dysphoric disorder (PMDD) when the drug only is administered from ovulation to menstruation only, which indicates an onset of action of 10 days or less. How fast this effect appears in terms of hours or days is, however, not known. The objective of this study was to explore this issue.

Intervention(s) in this Clinical Trial

• Drug: paroxetine
  • Capsules containing either placebo or paroxetine 20 mg. The treatment start after ovulation and when the subject has experienced premenstrual irritability for 2 days. The dosage is one capsule daily at 8 AM

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Paroxetine 20mg during the luteal phase of the menstrual cycle
• Placebo Comparator: 2
  • Placebo during the luteal phase of the menstrual cycle

Primary Measures

• The number of patients reaching sustained remission (irritability) for each time point

Secondary Measures

• Self rated irritability at each time point

Inclusion Criteria:

• The patient should have participated in an ongoing placebo-controlled trial regarding the effect of paroxetine in PMD; to be included in that trial, she must have fulfilled the diagnostic criteria A-C of PMDD in DSM-IV and certain other inclusion and exclusion criteria which are listed in appendix 1.
• The patient should a) have been given paroxetine during the previous trial, b) have reported that she has been "much improved" or "very much improved" by this treatment, c) have displayed a marked reduction in VAS-rated irritability during treatment, and d) have reported that she has found the side-effects tolerable.
• The patient should display at least a 50% increase in VAS-rated irritability during the luteal phase (mean of last five days prior to menses) as compared the follicular phase (days 6-10) during one cycle of pretreatment symptom rating (without medication).
• The patient should have given written informed consent to participate in the study.

Exclusion Criteria:

• Any concomitant psychiatric disorder for which SRIs are known to be effective.
• Any other concomitant psychiatric disorder that, in the investigator's opinion, would render the patient unsuitable for the study.
• Any somatic disorder that, in the investigator's opinion, would render the patient unsuitable for the study.
• Any ongoing medication which, in the opinion of the investigator, would render the patient unsuitable for the study. Examples of medications that preclude participation in the study are: 1) any psychotropic drug, with the exception of the occasional use of hypnotics, 2) any hormonal preparation, with the exception of thyroid hormone, 3) anti-coagulants, and 4) 5HT1D agonists. Occasional use of analgesic compounds does not preclude participation.
• Patient characteristics which, in the opinion of the investigator, are likely to reduce compliance with the protocol.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Karolinska Institutet

Overall Clinical Trial Officials and Contacts

Mikael SG Landen, MD, PhD Principal Investigator Karolinska Institutet, Stockholm, Sweden  

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00516113

Study ID Number: L&E-5

ClinicalTrials.gov Identifier: NCT00516113

Health Authority: Sweden: Medical Products Agency