A Placebo-Controlled Study to Investigate the Onset of Action of Paroxetine in Premenstrual Dysphoria

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 Overview

• Status: Completed
• Conditions: Premenstrual Dysphoric Disorder; Premenstrual Syndrome
• Intervention / Treatment: Drug: paroxetine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Göteborg, Sweden, SE43180
    • The Psychiatric clinic, Sahlgrenska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Paroxetine 20mg during the luteal phase of the menstrual cycle	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
Placebo Comparator: 2; Placebo during the luteal phase of the menstrual cycle	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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Self rated irritability at each time point

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Novo Nordisk A/S; GlaxoSmithKline; Göteborg University
• Investigators: Principal Investigator: Mikael SG Landen, MD, PhD, Karolinska Institutet, Stockholm, Sweden

Study record dates

Study Major Dates

• Study Start: October 1, 2000
• Study Completion (Actual): November 1, 2002

Study Registration Dates

• First Submitted: August 13, 2007
• First Submitted That Met QC Criteria: August 13, 2007
• First Posted (Estimate): August 14, 2007

Study Record Updates

• Last Update Posted (Estimate): December 7, 2007
• Last Update Submitted That Met QC Criteria: December 6, 2007
• Last Verified: August 1, 2007

More Information

Terms related to this study

• Keywords: paroxetine; onset of action; serotonin reuptake inhibitors
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Mood Disorders; Depressive Disorder; Menstruation Disturbances; Premenstrual Dysphoric Disorder; Premenstrual Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Paroxetine
• Other Study ID Numbers: L&E-5