A Review of Treatment and Management Modalities for Premenstrual Dysphoric Disorder

Transcription

1 A Review of Treatment and Management Modalities for Premenstrual Dysphoric Disorder KELLI KELDERHOUSE, MSN, RN, FNP-C JULIE SMITH TAYLOR, PhD, RN, WHNP-BC

2 Approximately 5 percent to 8 percent of women of childbearing age experience premenstrual dysphoric disorder (PMDD), which results in significant impairment of daily functioning during the week preceding menses each month. Abstract: Premenstrual dysphoric disorder (PMDD) affects 5 to 8 percent of women and can significantly decrease their quality of life. Symptoms generally present during the late luteal phase of the menstrual cycle and can affect women emotionally, behaviorally, cognitively and physiologically. This article reviews the clinical literature on PMDD and the evidence behind various methods of symptom management. Evidence suggests that a holistic approach, including lifestyle modifications, pharmacotherapy and cognitive behavioral therapy, is most beneficial for symptom reduction and improvement in daily functioning and quality of life. DOI: / X Keywords: PMDD PMS premenstrual dysphoric disorder

3 The burden of illness for women experiencing PMDD is significant and can disrupt parenting, relationships with significant others, career roles and work productivity (Pearlstein & Steiner, 2007). Differentiating between premenstrual syndrome (PMS) and PMDD has presented many challenges to researchers and clinicians. Diagnostic criteria differentiating PMS and PMDD have been outlined by the American Psychiatric Association (APA, 2000), the American College of Obstetricians and Gynecologists (ACOG, 2000) and the World Health Organization (WHO, 1992). While PMS presents many challenges with regard to diagnosis and treatment, the focus of this clinical review will be the treatment of PMDD. The ultimate goal of treatment for women affected by PMDD is for health care providers to rule out other diagnoses with similar symptomatology, so that individualized, effective management and treatment can be provided. Determining the most efficacious treatment has been disputed within the literature, as some women may not experience relief of symptoms despite purported effectiveness of a particular treatment in other women. Moreover, while some accepted pharmacologic therapies used in the treatment of PMDD have demonstrated success, many women remain without adequate relief from PMDD symptoms (Halbreich et al., 2006). With such a wide array of somatic and affective symptoms, effective treatment can be a challenge for clinicians, leaving many women without relief. To date, treatment options discussed in the research literature include pharmacologic agents (selective serotonin reuptake inhibitors [SSRIs], anxiolytics/benzodiazepines, nonsteroidal anti-inflammatory drugs, medications to suppress ovulation and combined oral contraceptive pills), cognitive behavioral therapy, lifestyle modifications, dietary alterations including supplements, stress management and exercise (Braverman, 2007). The purpose of this article is to review PMDD and provide an update for available PMDD treatment options. Literature Review Several Internet database search engines including Academic Search Premier, CINAHL with full text and EBSCO host were used to collect research reports to be included in this review. Key words included premenstrual dysphoric disorder, treatments, management and treatment guidelines. Additional information was collected using the North Carolina AHEC Kelli Kelderhouse, MSN, RN, FNP-C, is a family nurse practitioner at Wilmington Health Access for Teens in Wilmington, NC. Julie Smith Taylor, PhD, RN, WHNP-BC, is an associate professor and graduate coordinator in the School of Nursing at the University of North Carolina Wilmington in Wilmington, NC. The authors report no conflicts of interest or relevant financial relationships. Address correspondence to: taylorjs@uncw.edu. BOX 1 Physical, Psychological and Behavioral Symptoms of PMS and PMDD Physical Abdominal bloating Body aches Breast tenderness/fullness Cramps, abdominal pain Fatigue Headaches Nausea Swelling of extremities Weight gain Digital Library, including the PubMed database, using similar search terms as mentioned previously. Search dates were limited to the previous 5 years unless authoritative guideline revisions had not been published more recently. The majority of research information included in this review was obtained from evidence-based guidelines, systematic reviews, consensus statements and a few cohort and case controlled studies. Defi ning PMDD Psychological and Behavioral Anger, irritability Anxiety Changes in appetite (overeating, cravings) Changes in libido Depressed mood Feeling out of control Mood swings Poor sleep, or increased need of sleep Tension Social withdrawal from usual activities Note: The symptoms highlighted in bold lettering are comparable to the top four defining criteria for PMDD according to the DSM-IV-TR. Source: Biggs and Demuth (2011). PMDD refers to a set of negative physiologic, emotional, behavioral and cognitive symptomatic changes that significantly impair daily functioning during the late luteal phase of the menstrual cycle. The severity of symptoms and the significant impairment of daily functioning are what set PMDD apart from PMS. Some authors write about PMS and PMDD as one entity, while others clearly differentiate between the two disorders, and some view the two along a continuum. There are characteristic physical, psychological and behavioral symptoms characteristic of PMS and PMDD (see Box 1). 296 Nursing for Women s Health Volume 17 Issue 4

4 Specific criteria need to be present for a diagnosis of PMS and PMDD based on the number of symptoms present and the severity of the symptoms (Braverman, 2007). These criteria overlap with those in the DSM-IV-TR for PMDD; however, PMDD emphasizes problems with mood and highlights more severe mental health and emotional symptoms with a potential for more dysfunction within women s lives. Although many symptoms have been reported throughout the research in association with PMDD, at this time the diagnostic criteria set forth in the DSM-IV-TR best explain the inclusion criteria and length of time required to properly diagnose this disorder (see Box 2). cycle (Perez-Lopez, Chedraui, Perez-Roncero, Lopez-Baena, & Cuadros-Lopez, 2009). Much work has been done in the last 15 years to establish accurate diagnostic criteria, definitions and classifications of premenstrual disorders (O Brien et al., 2011). In September 2008, an inaugural meeting of the International Society for Premenstrual Disorders (ISPMD) was held in Montreal with experts among the field in women s health, particularly premenstrual disorders, to provide consensus on diagnostic criteria for premenstrual disorders, their quantification and guidelines on clinical trial design (O Brien et al., 2011). The primary aim of this group was to offer criteria to guide discussions of the next edition of the WHO s International Classification of Diseases (ICD-11), and the APA s Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V), currently under consideration at the time of this writing. Indeed, recommended criteria for PMDD for the DSM- V are recommended by the Mood Disorders Work Group as this The burden of illness for women experiencing PMDD is significant and can disrupt parenting, relationships with significant others, career roles and work productivity Diagnosing PMDD An accurate diagnosis of PMDD is facilitated by a 2-month record of prospective symptom charting by women, which affords clinicians the opportunity to determine the timing of symptoms and any cycle-to-cycle variability in symptomatology. The most well-established and widely used system for reporting symptomatology is the Daily Record of Severity of Problems (DRSP; O Brien et al., 2011). The primary focus of this instrument is on psychological symptoms, a hallmark of PMDD, and assists clinicians in determining the timing of symptoms, which usually start any time in the 2 weeks prior to the onset of menstruation, continuing to the start of flow and resolving within a day or two after this onset. Use of this instrument likewise provides documentation to rule out other affective disorders that may occur without relation to the menstrual disorder becomes a full diagnostic category, as opposed to listed in appendix B of the DSM-IV, Criterion Sets and Axes Provided for Further Study (Epperson et al., 2012). Again, this is important for many reasons, including the participation of women in more rigorous randomized clinical trials focused on pathophysiology, the addition of pharmacologic agents approved by the U.S. Food and Drug Administration (FDA), as well as agencies in other countries, thereby making PMDD a definitive diagnosis (Epperson et al.) possibly amenable to treatment (see Box 3). Etiology of PMDD The definite etiology of PMDD is not known and seems to be multifactorial. Biological theories include dysregulation of the serotonergic system, declining levels of ovarian steroid hormones during the late luteal phase of the cycle, endogenous opioid activity in the late luteal phase and genetic components (Di Giulio & Reissing, 2006). It is the change in, not the level of, reproductive hormones that triggers symptoms in those women with PMDD. Further, these women do not have abnormal August September 2013 Nursing for Women s Health 297

5 levels of reproductive hormones, but they are more sensitive to the shifts in them prior to menstruation (Anonymous, 2008). With regard to genetics, 93 percent concordance rates of PMS have been cited for monozygotic twins as compared to 44 percent among dizygotic twins (Braverman, 2007). While symptomatology was not specific to PMDD, Vigod, Ross, and Steiner (2009) found in a study of 1,000 female twins that there was an estimated hereditability rate of 50 percent of symptoms related to PMS. However, a prospective study following 1,488 women ages 14 to 24 over 42 months found environmental factors contributory to the development of PMDD, including traumatic events, such as sexual abuse in childhood, severe accidents and other physical threats (Braverman, 2007). Additionally, current research is examining the impact of specific genes in regards to certain personality traits of PMDD BOX 2 Diagnostic Criteria for PMDD A. Symptoms must occur during the week before menses and remit a few days after onset of menses. Five of the following symptoms must be present and include at least one of 1 to Depressed mood or dysphoria 2. Anxiety or tension 3. Affective lability 4. Irritability 5. Decreased interest in usual activities 6. Concentration difficulties 7. Marked lack of energy 8. Marked change in appetite, overeating or food cravings 9. Hypersomnia or insomnia 10. Feeling overwhelmed 11. Other physical symptoms (e.g., breast tenderness, bloating) B. Symptoms must interfere with work, school, usual activities or relationships. C. Symptoms must not merely be an exacerbation of another disorder. D. Criteria A, B and C must be confirmed by prospective daily ratings for at least two consecutive menstrual cycles. Source: Diagnostic and Statistical Manual of Mental Disorders (4th ed., text revision, 2000). Copyright 2000 by the American Psychiatric Association. patients (Gingnell, Comasco, Oreland, Fredrikson, & Sundstrom-Poromaa, 2010). These authors pose a genetic vulnerability for those with PMDD, and that development and severity of the disorder is related to neurobiological risk factors similar to major depression. The specific genetic coding for serotonergic 5HT1A receptor and the estrogen receptor alpha gene (ESR1) have shown potential genetic involvement from recent association studies (Cunningham, Yonkers, O Brien, & Eriksson, 2009). There may be a relationship between a polymorphism in the serotonin transporter gene and the severity of symptoms of PMDD (Taylor, 2005). Other authors propose that there is some evidence to suggest psychological involvement in the etiology of PMDD (Di Giulio & Reissing, 2006). To date, the most systematically studied treatments have been related to the elimination of hormonal fluctuations with ovulation suppression treatments, or the correction of neurotransmitter dysregulation with antidepressant or anxiolytic medications (Pearlstein & Steiner, 2007). However, much of the literature focuses on serotonin as the most recognized component involved in the etiology and treatment of PMDD with confirmation of SSRIs as a first-line pharmacologic treatment option. Burden of Illness PMDD is considered a chronic illness, not remitting until menopause (Johnson, 2004). The impact of PMDD on quality of life is an important aspect to the defining criteria of this disorder. Two studies were reviewed utilizing web-based methods with surveys and questionnaires evaluating the impact of PMDD on work absenteeism and productivity, and health-related quality of life, respectively. Yang et al. (2008) found that the burden of PMDD on health-related quality of life was greater than that of back pain, and similar to Type II diabetes, hypertension, rheumatoid arthritis and somewhat similar to depression. There are limitations to this study including a retrospective data collection process, questionable validity of data gathered online and the generalization of diseases used for comparison to PMDD with reference to gender and age. Heinemann, Minh, Filonenko, and Uhl-Hochgraber (2010) concluded that PMDD is associated with work productivity impairment and absenteeism, thus, posing a potential economic burden for society and women. Employed women who were classified as having moderate to severe PMS/PMDD had higher rates of productivity impairment and efficiency, as well as higher rates of absenteeism, as shown by results from all tools and questionnaires compared to those women with no symptoms or mild PMS. Limitations of this study also include generalizability to other settings, nonrandomized samples and a high dropout rate. Symptom Management Because the etiology of premenstrual disorders remains unclear, the goal of treatment is symptom management and reduction. 298 Nursing for Women s Health Volume 17 Issue 4

6 BOX 3 Recommended Criteria for the DSM-V by the Mood Disorders Work Group A. Symptoms must occur during the week before menses and remit a few days after onset of menses. Five of the following symptoms must be present and include at least one of 1 to Marked affective lability (e.g., mood swings; feeling suddenly sad or tearful or increased sensitivity to rejection) 2. Marked irritability or anger or increased interpersonal conflicts 3. Markedly depressed mood, hopelessness or self-deprecating thoughts 4. Marked anxiety, tension, feeling keyed up or on edge 5. Decreased interest in usual activities 6. Concentration difficulties 7. Marked lack of energy 8. Marked change in appetite, overeating or food cravings 9. Hypersomnia or insomnia 10. Feeling overwhelmed or out of control 11. Other physical symptoms (e.g., breast tenderness, bloating) B. Symptoms must interfere with work, school, usual activities or relationships (e.g., avoidance of social activities, decreased productivity and efficiency in any of the settings). C. Symptoms must not merely be an exacerbation of another disorder (although it may co-occur with other disorders). D. Criteria A, B and C must be confirmed by prospective daily ratings for at least two consecutive menstrual cycles. E. The symptoms are not due to the physiological effects of a substance (e.g., an abused drug, a medication or other treatment) or a general medical condition (e.g., hyperthyroidism). Note: Note the difference in the arrangement of 1 through 4 in Section A (from Box 2). Also, note the addition of letter E among the defining criteria. Source: Epperson et al. (2012). August September 2013 Nursing for Women s Health 299

7 While pharmacologic management of PMDD has been studied quite extensively, the first mode of treatment for PMDD is nonpharmacologic approaches, including lifestyle modification, dietary manipulation, herbal remedies, mineral supplementation and acupuncture. The literature suggests that these therapies may be most beneficial for those women with mild symptoms or who may not desire pharmaceutical methods. Lifestyle Lifestyle modification may include regular aerobic exercise for 30 minutes three to four times per week, avoiding stressful events and occasions leading up to the menstrual cycle and establishing a regular sleeping pattern, especially during the premenstrual period (Vigod, Ross, & Steiner, 2009). However, others have suggested that there is no evidence-based research to support exercise for the treatment of PMS and PMDD, but it may be recommended for overall good health (Biggs & Demuth, 2011). Additionally, self-help groups and professionally led counseling sessions incorporating diet, exercise and a positive reframing of a woman s perceptions of her menstrual cycle was beneficial in reducing symptoms when compared to a control group (Pearlstein & Steiner, 2007). These authors further state that there have been few studies on lifestyle modification and psychosocial treatments; therefore, it is difficult to determine which methods are most helpful. Diet and Supplements Dietary modification recommendations include limitation of salt, caffeine, chocolate, alcohol and fat (Andrzej & Diana, 2006). These recommendations are based on a literature review of current data and clinical experience and expertise. Furthermore, the dietary measures are advised for 2 to 3 months to alleviate or eradicate symptoms if they are mild, and until hormonal diagnosis can be made. These authors included PMS and PMDD together as one entity throughout their research and did not discuss the differentiation by severity of the conditions. Additionally, increasing the daily intake of complex carbohydrates may be helpful due to raising the levels of tryptophan, the precursor to serotonin, which is widely implicated in the etiology and treatment of PMDD (Cunningham et al., 2009). Dietary supplements have also been recommended for the treatment of PMDD, including calcium, magnesium, vitamin B6, tryptophan and vitamin E (Braverman, 2007). Pearlstein and Steiner (2007) report on the findings of various studies and found that calcium in a dose of 600 mg twice daily had an efficacy rate of 48 percent for emotional and physical symptoms of PMDD, compared with a rate of 30 percent for placebo, and they believe this supplement deserves further study. Additional evidence reported efficacy for tryptophan and vitamin E and suggest further study for replication for these supplements as well (Pearlstein & Steiner, 2007). Others report supplementation with high intake of calcium (1,200 mg) and vitamin D for symptom reduction of PMS and PMDD; however, the evidence is still considered quite limited (Biggs & Demuth, 2011). Large doses of vitamin B6 (greater than 300 mg) may be associated with peripheral neuropathy, and doses higher than 100 mg 300 Nursing for Women s Health Volume 17 Issue 4

8 showed no greater response than those below 100 mg; therefore, 50 to 100 mg per day may be recommended for premenstrual symptoms (Biggs & Demuth, 2011). Some herbal remedies may be useful in symptom reduction including Gingko biloba, Crocus sativus and the most extensively studied Vitex agnus castus (Dante & Facchinetti, 2011). In a randomized controlled trial, 40 drops of Vitex agnus castus administered for 6 days prior to menses, over six consecutive cycles, significantly reduced some premenstrual symptoms compared to placebo (Zamani, Neghab, & Torabian, 2012). Similarly, women treated with 20 mg of Vitex agnus castus per day were more likely to have a decrease in premenstrual symptoms including irritability, mood swings, anger, headache and breast fullness (Biggs & Demuth, 2011). Symptoms such as irritability and anger, especially prevalent with PMDD, may be amenable to the use of Vitex agnus castus as an adjunct to treatment. In contrast, St. John s Wort and evening primrose oil yielded no different results on effectiveness for symptom reduction as compared with placebo. effective results for women with PMDD since cognitive behavioral therapy is aimed at restructuring behaviors to improve daily functioning and the diagnostic criteria for PMDD include aspects of impaired functioning. Lustyk et al. (2009) performed a systematic review of seven peer-reviewed studies and reported efficacy of cognitive behavioral therapy for the treatment of PMS and PMDD; however, criticism of these studies included lack of control groups, the fact that only three were randomized controlled trials and effect sizes were small and not comparable to pharmacotherapy studies, thus, reducing reliability and validity. Pearlstein and Steiner (2007) also cite studies with documented effectiveness of cognitive behavioral therapy; however, another randomized controlled trial reported by these authors showed increased effectiveness is proven with combination therapy of SSRIs and 10 cognitive behavioral therapy sessions for PMDD when evaluated at 1 year poststudy, compared to treatment with an SSRI alone. Overall, it appears that evidence is suggestive of a therapeutic benefit for women receiving cognitive While pharmacologic management of PMDD has been studied quite extensively, the first mode of treatment for PMDD is nonpharmacologic approaches, including lifestyle modification, dietary manipulation, herbal remedies, mineral supplementation and acupuncture Acupuncture Acupuncture, as a complementary therapy, may be beneficial in alleviating milder symptoms associated with PMS. Symptom improvement has been documented in studies comparing actual acupuncture with sham acupuncture (Kim, Park, Lee, & Lee, 2011). Additionally, comparisons of acupuncture to different doses of progestin and anxiolytics also supported the use of this method. However, Kim et al. (2011) highlight methodologic flaws that weaken the evidence as presented. Cognitive Behavioral Therapy Cognitive behavioral therapy is a form of psychotherapy that focuses on the modification of disruptive thoughts, behaviors and emotions (Lustyk, Gerrish, Shaver, & Keys, 2009). Cognitive behavioral therapy can theoretically be effective in the treatment of PMS and PMDD because efficacy has been demonstrated in the management of other affective and somatic disorders, such as anxiety and pain. The goals of this form of therapy are to identify and restructure learned behaviors and thought processes that have proven disruptive, to help people recognize and cope with triggers, in hopes of improving daily functioning in problem areas. This would seem to provide behavioral therapy; however, study limitations have been cited. Additional evidence is suggestive of combination therapy with pharmacologic agents (SSRIs) and cognitive behavioral therapy. SSRIs The literature clearly emphasizes and supports the usage of SSRIs as first-line pharmacologic management of PMDD. The conclusions are multifaceted and efficacy of SSRIs on physical, behavioral and emotional symptoms is dependent upon type of medication, intermittent or continuous dosing schedules and various dosages of the particular SSRI medication utilized. Studies report efficacy rates of 60 percent to 90 percent for active treatment as compared with 30 percent to 40 percent for placebo (Cunningham et al., 2009). With regard to individualized treatment and specific symptom profiles, studies have shown higher efficacy rates, as high as 80 percent to 90 percent, for those women reporting irritability and related symptoms (Halbreich et al., 2006). Again, with irritability being a hallmark symptom of PMDD, these treatments might prove to be helpful in decreasing symptoms. Pearlstein and Steiner (2007) cite 12 trials with continuous dosing (full menstrual cycle) with fluoxetine, sertraline, August September 2013 Nursing for Women s Health 301

9 paroxetine, citalopram and fluvoxamine, and four trials with intermittent dosing schedules (from ovulation to onset of menstruation) of sertraline and citalopram. The review of these studies concluded equivalent efficacy for these two dosing schedules with the listed medications. Other studies reviewed by Pearlstein and Steiner (2007) have demonstrated lower success rates for intermittent dosing schedules with paroxetine for symptoms related to depressed mood, low energy, food cravings and somatic symptoms. In a meta-analysis including 29 SSRIs and 2,964 women, continuous dosing was shown to be more effective than intermittent schedules (Pearlstein & Steiner). These results indicate higher levels of evidence of care by utilizing meta-analysis, and good validity with a large sample size and the comparison of multiple drugs. With regard to specific dosages of SSRIs, some women may require lower dosages of these medications due to certain side effects. Two commonly reported side effects of SSRIs are decreased sexual desire and libido and weight gain. In a comparison trial between fluoxetine 20 mg and 60 mg, Pearlstein and Steiner (2007) found equal efficacy in the reduction of behavioral, physical and emotional symptoms, but the 20 mg dosage was better tolerated. Additionally, this was one of the first studies to demonstrate the more rapid onset of action in the reduction of physical symptoms related to PMDD. Indeed, SSRIs have been known to relieve irritability within days in women with PMDD; hence, the recommended luteal dosing schedules. However, researchers state the effects on other affective symptoms remain to be demonstrated (Steinberg, Cardoso, Martinez, Rubinow, & Schmidt, 2012). An improvement in sadness, anxiety and mood swings was noted in 12 women with PMDD who received 20 mg of fluoxetine during the luteal phase of menstruation, with peak improvements after 48 hours. Limitations to trials with SSRIs for the treatment of PMDD include the short-term duration of the studies, with most lasting 3 months. Long-term evidence-based treatment recommendations do not exist; therefore, further studies of pharmacologic treatments for PMDD are needed to evaluate long-term results. Women who discontinue taking SSRIs for PMDD may suffer recurrence of illness with exacerbation of symptoms. Drug effects such as tolerance to SSRIs, with women needing to switch medications and increase dosages, also would need to be examined in long-term trials. Finally, long-term adverse effects of these medications would need to be examined in relation to continuous versus intermittent dosing schedules as well as briefly mentioned titrated dosing throughout the cycle (Pearlstein & Steiner, 2007). A Cochrane review of SSRIs for reducing PMDD symptoms found that the evidence supports the use of these agents (Brown, O Brien, Marjoribanks, & Wyatt, 2009). Analyses found they were highly effective in treating physical, functional and behavioral symptoms. Additionally, both continuous and luteal phase dosing schedules were effective, and no influence of a placebo run-in period on the reduction in symptoms was observed. Fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and escitalopram were all effective in the reduction of symptoms. Combined Oral Contraceptives In reviewing the literature on combined oral contraceptives for the treatment of PMDD, the results were consistent and favorable for the usage of ethinyl estradiol and drospirenone (Pearlstein & Steiner, 2007). In 2006, the branded product YAZ received approval from the FDA for use as a treatment for PMDD for those women also desiring contraception. The pharmacologic constituents of YAZ are ethinyl estradiol 20 mcg and drospirenone 3 mg administered in a 24/4 day regimen. Although various dosages and intervals of ethinyl estradiol and drospirenone have been investigated, as well as intervals of pill versus placebo, women taking YAZ showed significant improvement of physical and mood-related symptoms when compared to those taking placebo (Pearlstein & Steiner). This may be due to an increased stability of hormone levels, as well as a reduction in withdrawal bleeding and related adverse symptoms (Pearlstein & Steiner). The pathophysiologic mechanism behind the efficacy of combined oral contraceptives for the treatment of PMDD has been attributed to antialdosterone and antiandrogenic properties of drospirenone, which blocks the androgenic hormone properties linked to increased irritability, a predominant symptom of true PMDD. Studies have investigated the effectiveness of combined oral contraceptives in PMDD and have included various symptoms and categories in their measurements. One particular investigation analyzed the largest study to investigate combined oral contraceptives to date and measured negative emotions, food cravings and water retention-related symptoms (Marr, Niknian, Shulman, & Lynen, 2011). Combined oral contraceptives were superior to placebo in the improvement of these symptoms during three cycles of treatment, with the greatest improvements observed in the first cycle. Another group of investigators compared oral contraceptives with and without drospirenone in the reduction of PMS and PMDD symptoms (Zervoudis et al., 2008). Breast tenderness and lack of self-control were both significantly reduced with both types of treatment. However, the subgroup taking the formulation with drospirenone did not show any premenstrual weight gain. Finally, Cochrane reviews on combined oral contraceptives containing drospirenone for premenstrual symptoms concluded that they may help in the treatment of PMDD (Lopez, Kaptein, & Helmerhorst, 2012). Two placebo-controlled trials using ethinyl estradiol and drospirenone found decreases after 3 months in impairment of productivity, social activities and relationships, all inherent to the psychological impairments of 302 Nursing for Women s Health Volume 17 Issue 4

10 PMDD. Lopez, Kaptein, and Helmerhorst (2012) concluded that placebo also had a large effect. They also suggested that evidence is lacking to determine the efficacy of combined oral contraceptives containing drospirenone after three cycles, in women with less severe symptoms, and if combined oral contraceptives are superior to other oral contraceptives. They recommend trials of better quality, both larger and longer, and using CONSORT guidelines (standards of research reporting). The National Guideline Clearinghouse includes the guideline title Non-contraceptive Uses of Hormonal Contraceptives (ACOG, 2010). PMDD is briefly mentioned in this guideline the percentage of women who responded favorably to SSRIs and combined oral contraceptives was actually less than the percentage of women with no response whatsoever. Therefore, alternative forms of treatment should be developed. Progesterone The Cochrane Collaboration has also reported on a review of progesterone for PMS (Ford, Lethaby, Roberts, & Mol, 2012). PMDD was not specifically mentioned in this review. Only two studies met the reviewer s inclusion criteria and both had significant limitations. The authors concluded that the trials did not show whether progesterone is an effective treatment for PMS, or if it is not. Neither trial revealed a subgroup of women who benefited from progesterone, nor examined claimed success with high doses. Cognitive behavioral therapy is a form of psychotherapy that focuses on the modification of disruptive thoughts, behaviors and emotions and includes the statement that combined oral contraceptives have been shown to reduce PMDD symptoms. One final note with regard to combined oral contraceptives for treating PMDD is the addition of ethinyl estradiol and drospirenone to the administration of antidepressants for premenstrual breakthrough depression (Cunningham et al., 2009). Although it may be appropriate to combine an oral contraceptive with an SSRI for those women with significant mood changes who have not responded to either treatment alone, there are limited data to support this recommendation (Pinkerton, Guico-Pabia, & Taylor, 2010). The combination of SSRIs and combined oral contraceptives in the treatment of PMDD has not shown better resolution of symptoms in numerous randomized controlled trials (Halbreich, 2008). Once the placebo effect was accounted for, Other Treatments Other forms of treatment for premenstrual symptoms have been studied; however, evidence-based data were lacking, or higher side-effect profiles were apparent. Some of these included gonadotropin-releasing hormone (GnRH) agonists, danazol, anxiolytics and bilateral oophorectomy (Pearlstein & Steiner, 2007). Anxiolytics have abuse potential, GnRH agonists and danazol must have add back estrogen replacement to prevent bone loss and are expensive, and surgery is invasive with its own unique set of risks and long-term morbidity and mortality. Additionally, other pharmacologic treatments have been mentioned in the literature, including spironolactone for swelling and bloating, as well as nonsteroidal anti-inflammatory drugs for body aches. Certainly, as with most distressing conditions, additional symptomatology can be addressed and treated with additional pharmacologic agents as appropriate. Implications for Clinicians Many women suffering from PMDD will first seek care from their primary health care providers for relief of their symptoms. August September 2013 Nursing for Women s Health 303

11 BOX 4 Interventions/Treatments for PMDD Interventions/Treatments Available SSRIs (luteal phase and continuous cycle dosing) (First-line pharmacotherapy) Combined oral contraceptives (First-line pharmacotherapy for women desiring contraception) Combination of SSRI and cognitive behavioral therapy (Increased effectiveness in combination) Vitex agnus castus (Evidence for adjunctive therapy) Dietary supplements (Calcium, magnesium, vitamin B6, tryptophan and vitamin E) Diet modifications (Limiting salt, caffeine, chocolate, alcohol and fat. Increasing complex carbohydrates raises levels of tryptophan, which is a precursor to serotonin) Lifestyle modifications (Regular aerobic exercise, avoid stress during luteal phase and good sleep hygiene) Evidence Available to Support Recommending Good Good Good Good Limited evidence, further study recommended Limited, recommended for milder symptoms often associated with PMS Limited, recommended for overall health Therefore, it is of utmost importance for clinicians, including nurses and advanced practice nurses, to stay abreast of current research in the field of women s health with regard to severe premenstrual related disorders. Unfortunately no universal treatment regimen for PMDD exists, and ideal algorithms and approaches are difficult to ascertain due to the many clusters of symptoms involved in this disorder (Perez-Lopez et al., 2009). The literature includes recommendations for the management of PMS and PMDD based mostly on expert opinion and experience. Most of these recommendations are given in a step-wise or hierarchal approach based on level of severity and symptomatology. Nurses and nurse practitioners are at the forefront of care and may often encounter patients who are suffering from PMDD. Women who receive evidence-based information and education will be more prepared to make treatment decisions most appropriate to their health belief system. Women who have suffered with PMDD symptomatology may feel despair if recommended treatments have not provided relief. It is only through continued, informed education, that women will continue to seek resolution of symptoms. Box 4 outlines existing strategies for treatment and management options available to women diagnosed with PMDD. Conclusion PMDD can have significant effects on quality of life for many women. Methods of managing the symptoms include lifestyle, cognitive behavioral therapy and pharmacologic agents, specifically SSRIs and combined oral contraceptives. Evidence obtained through randomized controlled trials indicates that the most effective interventions include pharmaceuticals that either inhibit serotonin reuptake or suppress ovulation (Pearlstein & Steiner, 2007). Although intermittent and continuous dosing schedules of SSRIs have been evaluated and shown to be effective, inconsistencies between studies exist. With many discrepancies and inconsistencies found in the published research literature, women s individual health histories and preferences should guide treatment. When nonpharmacologic management has been ineffective, pharmacologic management should be offered utilizing the lowest doses possible to minimize side effects. Nurses aware of the latest evidence can help counsel women in deciding on the most appropriate treatment regimen for them. NWH References American College of Obstetricians and Gynecologists (ACOG). (2000). ACOG practice bulletin: Premenstrual syndrome. Washington, DC: Author. American College of Obstetricians and Gynecologists (ACOG). (2010). ACOG practice bulletin: Noncontraceptive uses of hormonal contraceptives. Washington, DC: Author. American Psychiatric Association (APA). (2000). Diagnostic and statistical manual of mental disorders (4th ed.). DSM-IV-Text Revision. Washington, DC: Author. Andrzej, M., & Diana, J. (2006). Premenstrual syndrome: From etiology to treatment. Maturitas, 55(Suppl 1), S47 S54. doi: /j.maturitas Anonymous. (2008). Treatment for PMDD? New OC regime eyed. Contraceptive Technology Update, 29(11), Biggs, W. S., & Demuth, R. H. (2011). Premenstrual syndrome and premenstrual dysphoric disorder. American Family Physician, 84(8), Braverman, P. K. (2007). Premenstrual syndrome and premenstrual dysphoric disorder. Journal of Pediatric Adolescent Gynecology, 20, doi: /j.jpag Nursing for Women s Health Volume 17 Issue 4

12 Brown, J., O Brien, P. M. S., Marjoribanks, J., & Wyatt, K. (2009). Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database of Systematic Reviews, 2. doi: / cd pub.2. Cunningham, J., Yonkers, K. A., O Brien, S., & Eriksson, E. (2009). Update on research and treatment of premenstrual dysphoric disorder. Harvard Review of Psychiatry, 17(2), doi: / Dante, G., & Facchinetti, F. (2011). Herbal treatments for alleviating premenstrual symptoms: A systematic review. Journal of Psychosomatic Obstetrics and Gynecology, 32(1), Di Giulio, G., & Reissing, E. D. (2006). Premenstrual dysphoric disorder: Prevalence, diagnostic considerations, and controversies. Journal of Psychosomatic Obstetrics and Gynecology, 27(4), doi: / Epperson, C. N., Steiner, M., Hartlage, S. A., Eriksson, E., Schmidt, P. J., Jones, I., & Yonkers, K. A. (2012). Premenstrual dysphoric disorder: Evidence for a new category for DSM-5. American Journal of Psychiatry, 169(5), Ford, O., Lethaby, A., Roberts, H., & Mol, B. (2012). Progesterone for premenstrual syndrome. Cochrane Database of Systematic Reviews, 3. doi: / cd pub4. Gingnell, M., Camasco, E., Oreland, L., Fredrikson, M., & Sundstrom-Poromaa, I. (2010). Neuroticism-related traits are related to symptom severity in patients with premenstrual dysphoric disorder and to the serotonin transporter gene-linked polymorphism 5-HTTPLPR. Archives of Women s Mental Health, 13, doi: /s Halbreich, U. (2008). Selective serotonin reuptake inhibitors and initial oral contraceptives for the treatment of PMDD: Effective but not enough. CNS Spectrums: The International Journal of Neuropsychiatric Medicine, 13(7), Halbreich, U., O Brien, P., Eriksson, E., Bäckström, T., Yonkers, K. A., & Freeman, E. W. (2006). Are there differential symptom profiles that improve in response to different pharmacological treatments of premenstrual syndrome/premenstrual dysphoric disorder? CNS Drugs, 20(7), Heinemann, L. A., Minh, T. D., Filonenko, A., & Uhl-Hochgr aber, K. (2010). Explorative evaluation of the impact of severe premenstrual disorders on work absenteeism and productivity. Women s Health Issues, 20, doi: /j.whi Johnson, S. R. (2004). Premenstrual syndrome, premenstrual dysphoric disorder, and beyond: A clinical primer for practitioners. Obstetrics & Gynecology, 104(4), Kim, S. Y., Park, H. J., Lee, H., & Lee, H. (2011). Acupuncture for premenstrual syndrome: A systematic review and meta-analysis of randomized controlled trials. BJOG: An International Journal of Obstetrics & Gynaecology, 118(8), Lopez, L. M., Kaptein, A. A., & Helmerhorst, F. M. (2012). Oral contraceptives containing drospirenone for premenstrual syndrome. Cochrane Database of Systemtic Reviews, 2. doi: / cd pub4. Lustyk, M. K. B., Gerrish, W. G., Shaver, S., & Keys, S. L. (2009). Cognitive-behavioral therapy for premenstrual syndrome and premenstrual dysphoric disorder: A systematic review. Archives of Women s Mental Health, 12(2), doi: /s y Marr, J., Niknian, M., Shulman, L. P., & Lynen, R. (2011). Premenstrual dysphoric disorder symptom cluster improvement by cycle with the combined oral contraceptive ethinyl estradiol 20 mcg plus drospirenone 3 mg administered in a 24/4 regimen. Contraception, 84(1), doi: /j.contraception O Brien, P. M., Bäckström, T., Brown, C., Dennerstein, L., Endicott, J. Epperson, C. N., Yonkers, K. (2011). Towards a consensus on diagnostic criteria, measurement and trial design of the premenstrual disorders: The ISPMD Montreal consensus. Archives of Women s Mental Health, 14(1), doi: / s Pearlstein, T., & Steiner, M. (2007). Premenstrual dysphoric disorder: Burden of illness and treatment update. Journal of Psychiatry and Neuroscience, 33 (4), Perez-Lopez, F. R., Chedraui, P., Perez-Roncero, G., Lopez-Baena, M. T., & Cuadros-Lopez, J. L. (2009). Premenstrual syndrome and premenstrual dysphoric disorder: Symptoms and cluster influences. Open Psychiatry Journal, 3, Pinkerton, J. V., Guico-Pabia, C. J., & Taylor, H. S. (2010). Menstrual cycle-related exacerbation of disease. American Journal of Obstetrics & Gynecology, 202(3), doi: /j. ajog Steinberg, E. M., Cardoso, G., Martinez, P. E., Rubinow, D. R., & Schmidt, P. J. (2012). Rapid response to fluoxetine in women with premenstrual dysphoric disorder. Depression and Anxiety, 29, Taylor, D. (2005). Perimenstrual symptoms and syndromes: Guidelines for symptom management and self-care. Obstetrics & Gynecology, 5(5), Vigod, S. N., Ross, L. E., & Steiner, M. (2009). Understanding and treating premenstrual dysphoric disorder: An update for the women s health practitioner. Obstetrics & Gynecology Clinics of North America, 36(4), doi: /j.ogc World Health Organization (WHO). (1992). The ICD-10 Classification of mental and behavioral disorders. Clinical descriptions and diagnostic guidelines. Retrieved from Yang, M., Wallenstein, G., Hagan, M., Guo, A., Chang, J., & Kornstein, S. (2008). Burden of premenstrual dysphoric disorder on health-related quality of life. Journal of Women s Health, 17(1), doi: /jwh Zamani, M., Neghab, N., & Torabian, S. (2012). Therapeutic effect of Vitex agnus castus in patients with premenstrual syndrome. Acta Medica Iranica, 50(2), Zervoudis, S., Vladareanu, R., Galazios, G., Liberis, V., Tsikouras, P., & Veduta, A. (2008). Oral contraceptives with and without drospirenone in the treatment of premenstrual syndrome and premenstrual dysphoric disorder a multicentric study of 92 cases. Acta Endocrinologica ( ), 4(1), August September 2013 Nursing for Women s Health 305