Placebo-Controlled Trial Comparing Intermittent and Continuous Paroxetine in Premenstrual Dysphoric Disorder

Abstract

Serotonin reuptake inhibitors (SRIs) do not have to be administered continuously to be effective for premenstrual dysphoric disorder (PMDD), but can be given during luteal phases only. This is of practical importance, but also of theoretical interest since it suggests that the onset of action of SRIs is shorter in PMDD than in, for example depression. In this study, both continuous and intermittent SRI administration was compared with placebo, with the special purpose of analyzing if different PMDD symptoms respond differently depending on the treatment regimen. To this end, women meeting slightly modified DSM-IV criteria for PMDD (mean7SD age, 3776.3 years) were treated for three menstrual cycles with paroxetine continuously, paroxetine during the luteal phase only, or placebo, the population completing at least one treatment cycle comprising 55-56 subjects per group. Continuous treatment with paroxetine reduced premenstrual symptoms effectively with a response rate of 85%. The effect size was highest for irritability (1.4) and lowest for lack of energy (0.5). Intermittent treatment was as effective as continuous treatment in reducing irritability, affect lability, and mood swings, but had a somewhat weaker effect on depressed mood and somatic symptoms. The study indicates that the response rate when treating PMDD with SRIs is high, and that irritability is a key target symptom. Symptoms such as irritability, affect lability, and mood swings appear to be more inclined to respond rapidly to SRIs, enabling intermittent treatment, than are, for example, the somatic symptoms. Neuropsychopharmacology (2007) 32, 153-161.

Changes in mood, cognitive performance and appetite in the late luteal and follicular phases of the menstrual cycle in women with and without PMDD (premenstrual dysphoric disorder)

“…These dramatic cyclical changes in mood in women with PMDD have been well documented both clinically and in research studies (e.g. De Ronchi et al, 2005;Evans et al, 1998;Freeman et al 1985;Halbreich et al 1982;Landen et al, 2007;Rapkin et al 1989). …”

Premenstrual Dysphoric Disorder: Burden of Illness and Treatment Update

“…116 However, another study of 167 women with PMDD recently reported that, although both continuous and intermittent paroxetine were both superior to placebo for irritability, affect lability and mood swings, intermittent paroxetine was less effective than continuous paroxetine for depressed mood, low energy, food cravings and somatic premenstrual symptoms. 117 A recent meta-analysis of 29 SSRI studies in 2964 women concluded that continuous dosing is more effective than intermittent dosing for treatment of PMS and PMDD. 118 The seminal studies involving continuous dosing of SSRIs in PMDD involved relatively large samples.…”

Short Onset of Action of a Serotonin Reuptake Inhibitor When Used to Reduce Premenstrual Irritability

“…Suggesting that the onset of action of SRIs in PMDD is relatively short, it however soon became evident that a marked symptomreducing effect can be achieved also when the treatment is restricted to the interval during which symptoms are normally present. Such treatment, which starts at the time of ovulation, and stops shortly after the beginning of menses, is usually referred to as intermittent treatment (Sundblad et al, 1993;Halbreich and Smoller, 1997;Steiner et al, 1997Steiner et al, , 2005Jermain et al, 1999;Cohen et al, 2002;Freeman et al, 2004;Landén et al, 2006). It should however be noted that all premenstrual complaints are not equally inclined to respond to intermittent SRI administration.…”