Pearlstein 2005.

Methods	Randomised, double‐blind, placebo‐controlled 3‐arm parallel trial. Paroxetine CR 12.5 mg versus 25 mg versus placebo
Participants	Country: USA and Canada Site: 47 outpatient centres Recruitment: 1974 women screened, 371 randomised to Pearlstein. 125 randomised to paroxetine 25mg and 82 completed; 125 randomised to placebo, 96 completed.Mean age paroxetine 25mg 36.5±4.87 years, mean age of placebo 35.8±5.79 years Inclusion: Women aged 18‐45 years with regular menstrual cycles (22‐35 days) and confirmed PMDD based on DSM‐IV. Symptoms to have been present for at least nine out of previous twelve cycles over the previous year. Onset of severe premenstrual symptoms (as recorded on a daily basis) during the luteal phase was followed by symptom subsidence during the follicular phase based on four core symptoms (irritability, tension, affective lability and depressed mood). Required to demonstrate a 200% worsening on one core symptom or a 100% worsening on two or more symptoms during the luteal phase relative to the follicular phase. Baseline Clinical Global Impressions of Severity scale score >/3. Exclusion: Meeting DSM‐IV criteria for other Axis 1 disorder except specific phobias in the previous six months, diagnosed with gynaecological or other clinically significant disease, clinically significant depressive symptomology during the follicular phase, suicide risk, taking medication for PMD, received previous adequate treatment or participated in a clinical trial for PMDD, breastfeeding or pregnant. Using oral or systemic contraception.
Interventions	Screening: Two screening cycles Placebo run in: One cycle Intervention: Paroxetine 25mg taken orally in the morning throughout the cycle for three cycles versus placebo taken orally in the morning throughout the cycle for three cycles Timing of administration: No details as to which day of the cycle medication commenced. Placebo taken orally in the morning throughout the cycle for three cycles Summary measures: Treatment cycle 3 LOCF data
Outcomes	Visual Analogue Scale (VAS) recorded daily; Clinical Global Impressions of Severity scale (CGI‐S); Sheehan Disability Scale (SDS)
Notes	Symptoms rated daily Mean VAS score calculated by averaging the item score over the last five days of the luteal phase prior to menstruation Authors contacted, no response Funding GlaxoSmithKline
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation
Allocation concealment (selection bias)	Unclear risk	Method not reported
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Double blind, similar appearing medication, no details as to whom was blinded. Evidence that patients were blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	371 randomised and 325 analysed by ITT (87%). 12.5 mg group: 105/121 analysed for response (6 excluded, 12 adverse events, 4 loss to follow up, 2 protocol deviation, 5 other reason, 3 lack of efficacy) 25 mg group: 102/125 analysed for response (5 excluded, 20 adverse events, 10 loss to follow up, 5 protocol deviation, 3 other reason) Placebo:118/125 analysed for response (1 excluded, 9 adverse events, 3 loss to follow up, 5 protocol deviation, 8 other reason, 3 lack of efficacy)
Selective reporting (reporting bias)	Unclear risk	Does not state how adverse events data were collected
Other bias	Unclear risk	Placebo responders apparently excluded