title: The treatment of premenstrual syndrome with preparations of Vitex agnus castus: a systematic review and meta-analysis.
abstract: Premenstrual syndrome is characterized by the cyclic occurrence of physical, behavioral and psychological symptoms during the luteal phase of the menstrual cycle disappearing within a few days of the onset of menstruation. Generally symptoms are mild, but 5-8% of women suffer from severe PMS. Apart from conventional drugs, like serotonin reuptake inhibitors and oral contraceptives, complementary and alternative medicines such as Vitex agnus castus are used by many women experiencing PMS.
  
  
  
  Our objective was to determine the efficacy, tolerability, and acceptability of Vitex agnus castus preparations for treatment of premenstrual syndrome.
  
  
  
  All journals in the Ovid software from inception through January 2016 were searched, including the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and PsycINFO. Gray literature was searched by Google Scholar and manufacturers of Vitex agnus castus preparations were contacted for information about unpublished trials. We included randomized controlled trials with Vitex agnus castus in women with premenstrual syndrome and/or premenstrual dysphoric disorder with a minimal duration of 2 menstrual cycles. The eligibility of the manuscripts was assessed by 2 reviewers independently. The data abstracted included characteristics of the study design, characteristics of the patient population, intervention details, type of comparator, method of diagnosis, and outcome measures. We adhered to the PRISMA guidelines.
  
  
  
  We found 17 randomized controlled trials of Vitex agnus castus in the treatment of premenstrual syndrome. Fourteen of these could be included in the quantitative analysis. Thirteen of 14 studies with placebo, dietary supplements, or herbal preparations as controls reported positive effects of Vitex agnus castus on total premenstrual syndrome symptoms. Unfortunately most of the trials are associated with a high risk of bias. The pooled effect of Vitex agnus castus in placebo-controlled trials was large (Hedges g, -1.21; 95% confidence interval, -1.53 to -0.88), but heterogeneity was extremely high (I2, 91%). We were unable to single out factors that could explain this heterogeneity satisfactorily. The funnel plot and Egger tests suggest the presence of publication bias.
  
  
  
  Although meta-analysis shows a large pooled effect of Vitex agnus castus in placebo-controlled trials, the high risk of bias, high heterogeneity, and risk of publication bias of the included studies preclude a definitive conclusion. The pooled treatment effects should be viewed as merely explorative and, at best, overestimating the real treatment effect of Vitex agnus castus for premenstrual syndrome symptoms. There is a clear need for high-quality trials of appropriate size examining the effect of standardized extracts of Vitex agnus castus in comparison to placebo, selective serotonin reuptake inhibitors, and oral contraceptives to establish relative efficacy.
authors.forename: Saskia
authors.initials: S
authors.lastname: Verkaik
authors.affiliation: Epidemiological and Social Psychiatric Research Institute, Rotterdam, The Netherlands; Department of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Kamperman
authors.affiliation: Department of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Roos
authors.initials: R
authors.lastname: van Westrhenen
authors.affiliation: Mental Health Service Noord-Holland Noord, Specialized Treatment Division, Treatment Center for Bipolar Disorders, Alkmaar, The Netherlands.
authors.forename: Peter F J
authors.initials: PFJ
authors.lastname: Schulte
mesh_terms: D005260:Female; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D011293:Premenstrual Syndrome / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D020950:Vitex
chemical_list: D010936:Plant Extracts
keywords: Vitex agnus castus; meta-analysis; premenstrual syndrome; systematic review