British Journal of Obstetrics and Gynaecology
The efficacy of fluoxetine in improving physical symptoms associated with premenstrual dysphoric disorder
Introduction
Premenstrual dysphoric disorder, as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition1, is a severe variant of premenstrual syndrome (PMS). Premenstrual dysphoric disorder affects from 3% to 8% of women in their reproductive years2., 3., 4.. Premenstrual dysphoric disorder is characterised by a significant mood disturbance that appears during the week prior to onset of menses (the late luteal phase) and remits following the start of menstrual flow. The diagnosis of premenstrual dysphoric disorder requires persistence of this luteal mood disturbance, which includes tension, irritability, affective lability, and depression. Physical symptoms, such as breast tenderness, bloating, headache, and joint and muscle pain, frequently accompany the prominent dysphoria of premenstrual dysphoric disorder and contribute to occupational and social impairment during the late luteal phase of the menstrual cycle.
Many treatments have been utilised in the management of premenstrual symptoms, including hormonal therapies and, in the most severe cases, surgical intervention. More recently, the serotonergic agents, including specific serotonic reuptake inhibitors, have been shown to be effective at improving the mood symptoms associated with premenstrual dysphoric disorder5., 6., 7., 8., 9., 10., 11., 12.. Less has been described regarding their efficacy at reducing accompanying physical complaints. The current study evaluates data from a multicenter trial of the specific serotonergic re-uptake inhibitor fluoxetine in the treatment of premenstrual dysphoric disorder, specifically addressing physical symptomatology.
Section snippets
Methods
This was a randomised, double-blind, placebo-controlled, parallel study of 405 women, of whom 320 were randomised, designed to evaluated the efficacy of fluoxetine 20 mg/day and 60 mg/day in the management of premenstrual dysphoric disorder. The women were randomised to six menstrual cycles of double-blind treatment following a two-cycle, single-blind, placebo run-in period (Fig. 1). A detailed description of the study has been published previously12.
Results
Three hundred and twenty women (mean age, 36 ±5 years) with prospectively confirmed premenstrual dysphoric disorder were randomised to one of three treatment sequence groups: fluoxetine 20 mg/day (n=104), or fluoxetine 60 mg/day (n=108), or placebo (n=108). The treatment groups were comparable at baseline with respect to demographics.
Discussion
Daily fluoxetine treatment improved physical symptoms in women with premenstrual dysphoric disorder when symptoms were measured using a VAS physical scale, the individual VAS items (except headache), and the PMTS-SR and PMTS-O physical symptoms subtotals. Fluoxetine 20 mg/day produced similar improvement compared with fluoxetine 60 mg/day. This is the largest trial to date documenting that, in addition to improving mood, fluoxetine improved physical discomfort associated with premenstrual
Conclusion
Daily fluoxetine treatment significantly improved physical symptoms in women with severe premenstrual dysphoria. Fluoxetine treatment at 20 mg/day was as efficacious as 60 mg/day and was more tolerable than the higher dose. Future studies are required to determine whether intermittent fluoxetine dosing is as efficacious as daily fluoxetine dosing in improving physical symptoms associated with the premenstruum.
Acknowledgements
This work was funded by Eli Lilly Co.
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The premenstrual tension syndrome rating scales: An updated version
2011, Journal of Affective DisordersCitation Excerpt :The PMTS-SR has been translated into Portugese (Novaes et al., 1998) and both scales have been translated into German (Bergant et al., 2004) and Chinese (He et al., 2009). Both scales have been used as diagnostic and/or outcome measures in PMS clinical trials (Bloch et al., 1998; Brown et al., 1994; Casper et al., 1989; Chandraiah et al., 1991; Chuong et al., 1994; Chuong et al., 1997; Chuong and Hsi, 1994; Condon, 1993a; Critchlow et al., 2001; Critchlow et al., 2002; Cross et al., 2001; Daly et al., 2001; Deicken, 1988; Fontaine and Seal, 1997; Hahn et al., 1995; Haskett and Abplanalp, 1983; Khine et al., 2006; Kirkham et al., 1991; Lam et al., 1999; Lamarche et al., 2007; Maddocks et al., 1986; Masson and Gilbert, 1999; Mauri et al., 1988; Metcalf et al., 1989; Metcalf et al., 1990; Metcalf et al., 1991a; Metcalf et al., 1991b; Metcalf and Livesey, 1995; Novaes et al., 1998; Parry et al., 1995; Pearlstein et al., 2005; Rausch et al., 1988; Ravindran et al., 2007; Reame et al., 1992; Reid et al., 1986; Roca et al., 2002; Schmidt et al., 1991; Schmidt et al., 1993a; Schmidt et al., 1993b; Schmidt et al., 1998; Smith et al., 1987; Smith et al., 2002; Smith et al., 2003; Smith et al., 2004; Spencer et al., 2004; Steiner et al., 1995; Steiner et al., 2001; Steiner et al., 2003; Su et al., 1997a; Su et al., 1997b; Taskin et al., 1998; Winther and Hedman, 2002; Yonkers et al., 2005; Yonkers et al., 2006). It has been suggested that the use of the PMTS-SR score criteria alone might be sufficient to identify women for studies of severe PMS (Haskett and Abplanalp, 1983).
Histories of major depression and premenstrual dysphoric disorder: Evidence for phenotypic differences
2010, Biological PsychologyHormonal management of premenstrual syndrome
2008, Best Practice and Research in Clinical Obstetrics and GynaecologyCitation Excerpt :As a result, the benefit of spironolactone as a treatment for PMS is controversial due to inconsistent findings in studies. SSRIs, such as fluoxetine, sertraline, citalopram and paroxetine, have been shown to be very effective in the management of both physical and behavioural symptoms of PMS.46–51 The benefit of SSRIs can be observed in the first month of commencing therapy.