Myo-inositol in the treatment of premenstrual dysphoric disorder Carlomagno Gianfranco 1 *, Unfer Vittorio 1 , Buffo Silvia 2 and D’Ambrosio Francesco 3 1 AGUNCO Obstetrics and Gynecology Centre, via G. Cassiani, Rome, Italy 2 Casa di Cura Psichiatrica Colle Cesarano, Villa Adriana, Tivoli, Italy 3 Faculty of Medicine Tor Vergata University, Via Montpellier, Roma Objective Premenstrual dysphoric disorder (PMDD) is a mood disorder disrupting social and/or occupational life of affected women. Pre- menstrual dysphoric disorder etiology is unknown, although a pivotal role is played by the serotoninergic system. Indeed, one of the most effective treatments is selective serotonin reuptake inhibitors. Several studies have proposed a selective serotonin reuptake inhibitor-like role for myo-inositol, likely due to the fact that myo-inositol is the second messenger of serotonin. In the present study, we aimed to investigate the effect of myo-inositol in the treatment of PMDD. Methods We used a two-phase clinical trial approach (phase I: placebo washout; phase II: comparisons between treatment and placebo) and treated PMMD patients with two different myo-inositol formulations: powder or soft gel capsules. We decided to test these two formulations because according to the manufacturer, 0.6 g of myo-inositol in soft gel capsule has a pharmacokinetic equivalent to 2 g of myo-inositol in powder. Results Our results showed a significant improvement of three different scales: a reduction in the Daily Symptoms Records scale and an improvement of the Hamilton Depression Rating and Clinical Global Impression—Severity of Illness scales. Results were similar for both formulations. Conclusions In the present study, by using a new pharmaceutical formulation, we were able to clearly prove the efficacy of myo-inositol in PMDD. Copyright © 2011 John Wiley & Sons, Ltd. key words—myo-inositol; premenstrual dysphoric disorder; selective serotonin reuptake inhibitors; soft gel capsules INTRODUCTION Among all the natural molecules claiming to have an effect on mood disorders, myo-inositol is one of the few that has been proven effective (Saeed et al., 2007). The main challenge to the adoption of myo-inositol into clinical practice was the dosage. Indeed, several trials were performed using myo-inositol preparations ranging from 12 to 30 g, resulting in gastrointestinal side effects and reduced patients’ compliance (Rosel et al., 2000, Levine et al., 1995, Benjamin et al., 1995b, Carlomagno and Unfer, 2011). Premenstrual dysphoric disorder (PMDD) is a mood disorder affecting women during the last week of lu- teal phase (Zukov et al., 2010, Pearlstein and Steiner, 2008, Yang et al., 2008). PMDD is characterized by physical, affective, and behavioral symptoms, particu- larly anxiety and depressed mood that disrupt social and/or occupational functioning (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) (Halbreich et al., 2003, Chawla et al., 2002) (Borenstein et al ., 2005). PMDD affects from 2 to 8% of US or European women, and its diagnosis is based on two full monthly cycles of daily symptom charting (Cunningham et al ., 2009). Several studies suggest that the etiology of PMDD relies at least in part on decreases in serum progesterone and oestradiol levels; therefore, PMDD has been consid- ered to be a consequence of steroid withdrawal (Schmidt et al., 1998). Both animal experiments and clinical studies suggest that androgens may exaggerate irritabil- ity and aggression (Schmidt et al., 1998). Therefore, because irritability is the main symptom of PMDD (Schmidt et al., 1998), it has been suggested that PMDD may be partially due to enhanced androgenicity. Two lines of evidence support the assumption that the pathogenesis of PMDD may be related to changes in serotoninergic activity: first, the main symptoms of PMDD, such as irritability, anger, depressed mood, and carbohydrate craving are serotonin-dependent behaviors; second, aberrations in serotonergic transmis- sion were found in women with premenstrual syndrome/ *Correspondence to: C. Gianfranco, AGUNCO Obstetrics and Gynecology Centre, via G. Cassiani, Rome, 15–00155, Italy. E-mail: gianfranco. carlomagno@gmail.com Received 25 July 2011 Accepted 30 September 2011 Copyright © 2011 John Wiley & Sons, Ltd. human psychopharmacology Hum. Psychopharmacol Clin Exp 2011; 26: 526–530. Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/hup.1241