Effects of Antidepressants on Quality of Life in Women with Premenstrual Dysphoric Disorder

Transcription

1 Pharmacoeconomics 2005; 23 (5): CURRENT OPINION /05/ /$34.95/ Adis Data Information BV. All rights reserved. Effects of Antidepressants on Quality of Life in Women with Premenstrual Dysphoric Disorder Ellen W. Freeman Departments of Obstetrics/Gynecology and Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA Abstract This review examines the effects of antidepressant medications on premenstrual dysphoric disorder (PMDD) and the diminished quality of life (QOL) that accompanies the disorder. PMDD is a chronic condition in women that emerges in the second half of the menstrual cycle and remits during the menstrual period. The affective and behavioural symptoms of PMDD adversely affect functioning and QOL to a disabling degree, particularly in the domains of family and personal relationships, work productivity and social activities. The serotonergic antidepressants, specifically the selective serotonin reuptake inhibitors (SSRIs), are effective for PMDD. Continuous and luteal-phase dosing regimens with SSRIs are similarly effective and well tolerated. Treatment of PMDD with a serotonergic antidepressant significantly improves functioning and QOL in all studies that have systematically examined QOL issues in this disorder. Although the data show that PMDD is effectively treated with serotonergic antidepressants and that functional impairment that accompanies the disorder is also improved with treatment, the social and economic burden of PMDD continues to be widely unrecognised. Greater awareness of the effectiveness of treatments and reliable measures of the direct and indirect healthcare costs of the disorder when it remains untreated are needed. tioning to a disabling degree. The long-term nature of PMDD indicates the importance of effective treatment, not only for symptom reduction, but also for the impact on quality of life (QOL). The concept of health-related QOL (HR-QOL) has become a measure of growing importance in assessing healthcare interventions. QOL assess- ments are a means of identifying how the patient Premenstrual dysphoric disorder (PMDD) is a chronic disorder that is linked to women s menstrual cycles. The hallmark of PMDD is the occurrence of symptoms that emerge in the premenstrual phase of the cycle and remit following menses. Although many women experience premenstrual symptoms to a varying extent, PMDD is defined by affective and behavioural symptoms that adversely affect func-

2 434 Freeman criteria for a diagnosis of PMDD include the follow- ing: at least 5 of 11 indicated symptoms, including at least one of the mood symptoms, are severe premenstrually and abate postmenstrually; the symptoms markedly impair functioning; the symptoms are not an exacerbation of another physical or mental disorder; the symptoms are confirmed by daily ratings for at least two consecutive menstrual cycles. The 11 PMDD symptoms are depressed mood, anxiety/tension, mood swings, irritability/marked anger, decreased interest, difficulty concentrating, fatigue, appetite changes, sleep difficulties, feeling out of control and physical symptoms (evaluated as a single entity). In addition to the requisite symptom pattern linked to the menstrual cycle, the PMDD diagnosis requires functional impairment resulting from the symptoms and the exclusion of other emotional or physical disorders that could account for the symp- toms. It is this functional impairment, usually in the domains of personal relationships, work, school or social activities, that can lead to diminished QOL and has fuelled the search for treatments to provide symptom relief. The diagnosis of PMDD continues to be based on the patient s report of symptoms, with confirmation by prospective daily symptom reports maintained for two or more menstrual cycles. No laboratory test or other physiological measures identify the disor- der. By definition, women with PMDD have regular menstrual cycles, and ovarian hormone levels are usually in the normal range. Functional impairment is based on the patient s report of diminished abilities or increased distress in her personal relationships, work performance or ability to carry out daily activities. The mean age in most clinical samples of women with PMS/PMDD is in the mid-thirties, although these women typically report that the symptoms feels and functions in daily life, where not only the signs and symptoms of the disease but also changes in physical, psychological or social functioning or overall well-being are important. These domains of feeling and functioning are incorporated in the determination of HR-QOL. Moreover, because a diagnosis of PMDD includes the criterion of functional impairment, a determination of whether functioning has improved is a highly relevant measure of the success of treatment. This report reviews use of antidepressant medications in the treatment of PMDD with a focus on the effects on QOL, based on the current clinical litera- ture. The studies included in this review were identi- fied through searches of MEDLINE, EMBASE, PubMed (The National Center for Biotechnology Information), Science Citation Index, national meeting abstracts and reference lists. The search terms were premenstrual syndrome or premenstrual dysphoric disorder, with date limits of The term premenstrual syndrome (PMS) continues to be widely used in the medical literature, and the American College of Obstetrics and Gyne- cology recently issued clinical practice guidelines for the diagnosis and treatment of PMS. [1] For this reason, results from studies of antidepressant treat- ments for women with clinically significant or severe PMS were also included. The term PMDD is used where the PMDD diagnosis was clearly de- fined in the report. The term PMS is used when the study was defined as a study of PMS or when there was no clear diagnostic distinction between PMS and PMDD. More information on the respective definitions is provided in section Diagnosis and Epidemiology of Premenstrual Dysphoric Disorder (PMDD) The diagnostic criteria for PMDD are presented in the Diagnostic and Statistical Manual of Mental Disorders (4th Edition) [DSM-IV] [2] and are intended to diagnose a severe dysphoric form of PMS. The

3 Antidepressants and Quality of Life in PMDD 435 started as much as a decade earlier. [3] Although little women who completed prospective daily ratings for information is available from prospective, longitudi- two menstrual cycles), 5% met criteria for PMDD. [6] nal studies, clinical evidence suggests that PMDD An additional 13% had severe PMS symptoms but tends to be a chronic disorder that continues until did not have five symptoms to meet the requirement menopause. PMDD may theoretically begin at any for PMDD. In yet another community-based, pro- time after menarche, and significant premenstrual spective, longitudinal survey, 8% of menstruating symptoms have been identified in adolescents, [4,5] women had severe and 14% had moderate premen- but little else is known about the disorder in this age strual symptoms that were significantly associated group. The symptoms of PMDD are believed to with functional impairment. [11] In a population- remit during pregnancy but return with the resumpand based sample of 4164 women, 976 were interviewed tion of menstrual cycles. a subgroup of 513 women completed prospec- Although there is great variability among women tive daily symptom ratings for one menstrual cycle. in the type, severity and duration of symptoms, PMDD was confirmed in 6.4% of the women with individual cases appear to be stable from cycle to prospective symptom ratings. [12] In a survey of Ca- cycle in the short term, [6,7] although in the long term nadian women, 5% met the criteria for a diagnosis of there is frequently a gradual worsening over time. PMDD; an additional 21% marginally met the Longitudinal epidemiological data over a 4-year PMDD criteria by having the required number of symptoms rated moderate to severe. [13] These estiperiod indicated that there was <10% remission in mates are notably consistent, and are also consistent the baseline cases. [4] Several pilot studies of drug with clinical evidence that shows 3 8% of patients treatment showed that premenstrual symptoms remeet strict criteria for PMDD. [14] Many more woturned swiftly after discontinuation of medication. men experience clinically significant symptoms but In a double-blind, placebo-controlled trial, Yonkers fail to meet the specific criteria of the PMDD diaget al. [8] reported relapse rates after discontinuation of nosis. sertraline of 66% after three cycles with no medica- The incidence of PMDD and its clinical presentation, 66% after six cycles and 60% after nine cycles. tion in different cultures has not been systematically In another pilot study, PMDD patients who stopped studied. Available data suggest that PMS/PMDD fluoxetine after 6 months of treatment often relapsed occurs across cultures at similar rates, [15-19] although within one cycle. [9] In a 1-year naturalistic follow-up specific symptoms may be reported in one culture of PMS patients who were treated with sertraline, more than another. 77% of the women who discontinued sertraline reported [20-22] moderate-to-severe PMS symptoms after [20-22] 2. Productivity Loss, Resource Use and treatment withdrawal; 83% of those who reported a Costs Associated with PMDD return of symptoms indicated that this occurred within 3 months of stopping medication. [10] The morbidity of PMDD results from the severity The prevalence of PMDD in the population of of the symptoms, the chronic nature of the disorder, reproductive-age women was recently estimated at and the resulting impairment in work, relationships 6%, with an additional 19% identified as near- and activities. The level of impairment in the sympthreshold cases that failed to meet the strict PMDD tomatic phase of PMDD is significantly greater than criteria in a prospective longitudinal survey. [4] In community norms for a population sample, and is another study of menstrually related symptoms in a similar to that of women with depressive disorhealth maintenance organisation population (1194 ders. [23] The impairment of PMDD is significantly

4 436 Freeman correlated with the dysphoric mood symptoms of the severity of premenstrual symptoms increased, the disorder, [23,24] but does not appear to be associated likelihood of healthcare service use also increased with decrements in memory or learning. [25,26] for visits to the emergency department, obstetrician/ Women with PMS/PMDD report that of all areas gynaecologist or alternative medicine providers. [24] of impairment, the greatest impairment is in personhealthcare Women with PMS made significantly more visits to al relationships [23,27-29] and compromised work providers and were more likely to accrue levels. [23,28,30] One study found that 3.9% of the visit costs of over $US500 in a 2-year period women with PMS were absent from work once, and ( ) compared with women without PMS 2.1% were absent more than twice in a 6-month in a cross-sectional cohort study. [30] period. [31] Using a 1-year time frame, another study reported that half of women with PMDD indicated 3. Antidepressant Treatment for PMDD they missed work at least once and 6.5% missed work two to three times per month due to premen- 3.1 Serotonergic Antidepressants strual symptoms. [27] However, in another population-based study that included prospective daily Clinical Efficacy symptoms ratings to assess PMDD, there was little The serotonergic antidepressants, particularly the evidence of reduced time at work or other activities selective serotonin reuptake inhibitors (SSRIs) are in spite of decreased productivity and role limitathe first-line treatment for PMDD at this time. The tion. [24] US FDA has approved three SSRIs for the indica- Decreased productivity and role limitation clear- tion of PMDD: fluoxetine, sertraline and paroxetine. ly compromise the functioning of women with Modulating serotonergic function is consistent with PMDD. Halbreich et al. [32] calculated the burden of the dominant theoretical view that the normal gona- PMS/PMDD based on the Global Burden of Disease dal steroid fluctuations of the menstrual cycle trigmodel [33] and estimated 3.8 years of disability over ger an abnormal serotonergic response in vulnerable the reproductive years for each women with PMDD, women. [41] a sizable burden in public health that has received A meta-analysis of randomised, controlled trials little recognition to date. [32] of SSRIs for the treatment of PMS/PMDD conclud- Inadequate treatment of mood disorders in- ed that these drugs were an effective first-line thercreases the costs of medical care and lost productivi- apy, with a standard mean difference in favour of ty. [34,35] Even subsyndromal symptoms of dysphoric SSRIs equivalent to an odds ratio of 6.91 in terms of mood disorders are associated with increased medi- reducing overall PMS symptoms. [42] Secondary cal and mental health services. [36,37] Women who analysis showed that the SSRIs were as effective in report menstrual-related symptoms have poorer treating physical symptoms as behavioural symphealth status than women who do not report men- toms. [43] Efficacy in treating PMS/PMDD has been strual symptoms. [38] In another study, women who clearly shown in randomised, placebo-controlled, had lower scores on general well-being and had double-blind trials for the SSRIs fluoxetine, [44-50] premenstrual symptoms were more depressed 1 year sertraline, [51-56] paroxetine [57] and citalopram, [58] and later. [39] Results in a preliminary study indicated that venlafaxine [59] (which increases central activity of women with a diagnosis of PMDD were likely to both serotonin and norepinephrine [noradrenaline]) have a major depressive episode within 2 years. [40] A and clomipramine [60,61] (a tricyclic antidepressant population-based study of PMDD showed that as the with strong serotonergic activity). Small, open-label

5 Antidepressants and Quality of Life in PMDD 437 studies showed that the frequency of response to the review of 26 randomised, controlled trials of comserotonin receptor modulator nefazodone [62] and the plementary and alternative therapies concluded that SSRI fluvoxamine [63] for treatment of PMS was there was no convincing evidence of efficacy for similar to that of the placebo-controlled studies of PMS. [80] SSRIs Dosing Strategies and Tolerability of Selective While SSRIs are the first-line therapy for PMDD Serotonin Reuptake Inhibitors at this time, hormonal treatments, particularly oral Effective doses of SSRIs in reports of PMS/ contraceptives, are often prescribed, although con- PMDD treatment are consistently at the low end of sistent scientific evidence of efficacy for PMDD is the dose range for depression. [81] Response is usuallacking. A triphasic oral contraceptive was more ly swift, with evidence of improvement in the first effective than placebo only for the physical sympmenstrual cycle of treatment followed by smaller toms of breast pain and bloating. [64] A recent trial of increments of improvement with continued use or an oral contraceptive containing a new progestin, an dose adjustments in the next one to two cycles. An analogue of spironolactone, showed a consistent individual patient may respond better to one SSRI reduction of both physical and behavioural sympthan another and if the response is inadequate after toms including dysphoric mood, [65] but further study two to three cycles, a second SSRI should be trialwith sufficient statistical power is needed to confirm led. [82] No clear predictors of either response or or refute these findings. Gonadotropin-releasing adverse effects have been identified for SSRI treathormone agonists such as depot leuprorelin ment of PMDD at this time. [83] A thorough review of (leuprolide) [66,67] and intranasal buserelin [68,69] effecthe diagnosis and adjustments of the doses of meditively reduce PMS symptoms but are of limited use cation for the primary disorder should be considered because of the health risks associated with maintainbefore pursuing other treatments for PMDD. There ing low oestrogen levels. Although progesterone are no data available yet to show that non-respondtreatment for PMS has been advocated for many ers to SSRIs respond to other potentially useful years, more than 14 randomised, controlled trials medications such as anxiolytics or hormonal treathave failed to show improvement greater than placements, but this may be a logical next step for indibo for the mood and behavioural symptoms of vidual patients. PMS. [70] Limiting the period of administration of SSRIs Anxiolytics, specifically alprazolam and bus- such as fluoxetine [50] and sertraline [51,52] to the pirone, have shown modest efficacy for PMS in symptomatic luteal phase has been shown to be as some studies, [71-75] but not others. [76,77] These medi- effective as continuous dosing regimens for cations offer a possible alternative to SSRIs, but it is PMDD. [42] This avoids administration of medication important to recognise the conflicting and essential- during the symptom-free interval each month and ly weak results and the possible risk of dependency the choice of an intermittent or continuous dosing for alprazolam. regimen can be based on patient/clinician prefer- Numerous nonpharmacological approaches have ence. [84] Once-weekly administration in the two lubeen advocated for PMS, but few are supported by teal phase weeks with a sustained-release formulasolid empirical evidence. Calcium supplementation tion of fluoxetine (90mg, enteric coated) has also (1200 mg/day) reduced premenstrual symptoms been shown to be effective. [85] Several studies are more than placebo, [78] and several reports of cogni- currently investigating the efficacy of starting treattive therapies showed improvement of PMS. [79] A ment at symptom onset, which for many women

6 438 Freeman with PMS/PMDD is an even shorter time period than the 2-week luteal phase. This rapid response of PMS/PMDD patients to an SSRI is not well understood but suggests that the mechanisms of the disorder differ from those of major depression, which often requires weeks to achieve an effective response to SSRIs. The intermittent use of an SSRI only during the luteal phase raises questions about discontinuation symptoms that are known to occur with use of SSRIs in depression. [86] Discontinuation symptoms have not been reported in the published studies of this intermittent dosing regimen for PMS/PMDD, [52,87] but longer-term data specifically investigating this issue are still needed. Adverse effects of SSRIs when used for PMDD, although common, are typically transient, disappearing within the first one to two cycles of treat- ment. The most frequent adverse effects include headache, nausea, insomnia, fatigue or lethargy, di- arrhoea, decreased concentration, dizziness and decreased libido or delayed orgasm. [81] While sexual difficulties may emerge with the use of SSRIs, it is often difficult to determine wheth- er these are medication induced, particularly if there is no information about the status of the woman s sexual functioning prior to initiating the drug regimen. The incidence of decreased sexual interest or delayed orgasm associated with antidepressant treatment in the few published reports of patients with PMS/PMDD ranges from approximately 6% to 15%. [10,50] This incidence is notably lower than the rates of 36 43% in the general population of SSRI users. [88] In a multicentre trial of fluoxetine in an intermittent dose regimen for PMDD, systematic assessment of sexual function with the Arizona Sexual Experience Scale showed no significant impair- ment in sexual functioning compared with placebo. [50] Moreover, some women treated with an SSRI for PMS/PMDD report that sexual adverse effects diminish with time and adjustment to the medication although others do not. Diminished sexual function that results from antidepressant use may itself diminish QOL and also lead to discontinuation of a medication that had improved QOL by reducing PMDD symptoms. At this time, the information about sexual adverse effects related to use of an- tidepressants in women with PMS/PMDD is from short-term treatment trials and the extent of sexual dysfunction associated with long-term use of an- tidepressant medication in women with PMS/ PMDD warrants further study. 3.2 Other Antidepressants The antidepressant response in PMS and PMDD appears to be associated with potent serotonergic activity and is not a general antidepressant effect. This is indicated in clinical trials of tricyclic or other antidepressants, which are clearly effective for depressive disorders, but were not any more effective that placebo in studies of PMS/PMDD. The studied antidepressants that have not shown efficacy for PMS/PMDD include desipramine (a tricyclic noradrenergic antidepressant), [52] bupropion (a weak inhibitor of both serotonin and norepinephrine reuptake), [48] and maprotiline (a selective norepinephrine reuptake inhibitor). [57] 4. Antidepressant Treatment for PMDD and Quality of Life A number of reports have shown that PMDD impairs daily functioning, particularly relationships with family and coworkers, work productivity and other social activities. [27,32,38,89] The psychosocial burden of PMS/PMDD is similar to other depressive disorders. [23] Studies that have assessed the effects of SSRIs on QOL when used in the treatment of PMS or PMDD are summarised in table I. Substantial improvement in functional impair- ment was reported in randomised, placebo-con- trolled trials of sertraline for PMDD. [23,51-53,96] Func-

7 Table I. Summary of studies that measured quality of life (QOL) with antidepressant treatment for premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD). All studies were randomised and placebo controlled. All agents were given orally Diagnosis No. of Duration Drug Dosage QOL measure QOL results References subjects (menstrual cycles) PMDD Sertraline mg/day SAS, [90] Q-LES-Q [91] Significant improvement vs placebo for 23,53 DRSP [92] total scores, work, social activity, marital relationship, family unit and global QOL rating PMDD Sertraline mg/day SAS, [90] Q-LES-Q [91] Significant improvement vs placebo on 51 DRSP [92] total scores, productivity, interpersonal relationships and social activities PMS/PMDD Sertraline vs mg/day QOLS; [91] Global Sertraline but not desipramine showed 52 desipramine rating scales of significant improvement vs placebo for functioning QOLS, family relationships, work and social activity PMDD Fluoxetine 20 or 60 mg/day PMTS-SR [93] Significant improvement vs placebo on 89 overall functioning and work capacity for both dosages of fluoxetine PMDD Fluoxetine 90mg od or bid Sheehan Disability Significant difference vs placebo in twice- 85 Scale [94] daily dose group for work, social life and family life PMDD 17 6 Fluoxetine mg/day VAS Significant improvement vs placebo in 49 social impairment and work inefficiency PMDD Fluoxetine 10 or 20 mg/day DRSP; [92] ASEX [95] Significant improvement vs placebo in 50 social functioning; no significant changes in sexual experience items PMDD Fluoxetine 90mg at day 14 DRSP [92] Significant improvement vs placebo in 85 and day 21 social functioning in the group that received both doses ASEX = The Arizona Sexual Experience Scale; bid = twice daily; DRSP = Daily Record of Severity of Problems; od = once daily; PMTS-SR = Premenstrual Tension Scale selfrating; Q-LES-Q = Quality of Life Enjoyment and Satisfaction Questionnaire; QOLS = Quality of Life Scale; SAS = Social Adjustment Scale; VAS = visual analogue scale. Antidepressants and Quality of Life in PMDD 439

8 440 Freeman tional improvement was documented as significant surveys consistently show that functioning is imeffects on the following: all domains of the Social paired premenstrually, particularly in the domains of Adjustment Scale (SAS), [90] which assesses marital, family and personal relationships, work productivity parental and family relationships, work, housework and social activities. Clinical trials that have exand social activities; the Quality of Life Enjoyment amined functional status and QOL in PMS/PMDD and Satisfaction Questionnaire (Q-LES-Q); [91] and patients indicate that treatment with a serotonergic on patients global reports of functioning in relation- antidepressant improves functioning and QOL. Imships, productivity and social activities. [51-53] provement in these domains generally follows Within three cycles of treatment, 63% of patients symptom improvement and is relatively swift in receiving sertraline, compared with 46% of the pla- shorter-term treatment trials, which are typically of cebo group, were within 10% of the community 2 3 months duration. norm on the Q-LES-Q (significant with a chi-square 5. The Continuing Burden of test). [51] In a secondary analysis, functional improve- Premenstrual Syndrome/PMDD ment swiftly followed symptom improvement, which occurred in the first treatment cycle with Although data show that PMS/PMDD is effecactive medication. [23] In a comparison of luteal- tively treated with SSRIs and that functional impairphase versus continuous treatment with sertraline ment of the disorder is also improved, the burden of for PMDD, both treatment regimens resulted in sig- PMS/PMDD remains largely unrecognised. [32] Renificant improvement in QOL and functioning as sults of a survey that examined the diagnosis and assessed by the SAS and Q-LES-Q. [96] In this study, treatment of PMS in the US indicated that only one early symptom improvement (in the first cycle of in four physicians provided adequate treatment for active medication) significantly predicted improved PMS. [97] QOL. One issue that impedes recognition of the burden Fluoxetine has also been shown to improve funcdiagnosis of this disorder is the ongoing debate about the tioning of PMDD patients in randomised, placebofunctional of PMS and the extent to which it involves controlled trials. [49,50,85,89] Work capacity, as asthreshold impairment. Many women with a subcontrolled sessed by eight items from the self-rated Premenpremenstrual PMDD diagnosis seek treatment for their strual Tension Scale (PMTS-SR), [93] improved symptoms and report functional imstrual swiftly in the first fluoxetine-treated cycle and not in pairment. The numbers of women who fail to meet the placebo-treated cycles. [89] Social functioning as the stringent PMDD criteria suggest that the burden assessed by the Daily Record of Severity of is considerably greater than that identified by Problems (DRSP) improved significantly more with PMDD. [4,6,11,13,32] fluoxetine than placebo treatment. [50,85] Work, family life and social life as assessed by the Sheehan 6. Conclusions Disability Scale [94] improved significantly more Serotonergic antidepressants are currently the with fluoxetine than placebo treatment. [85] Patient first-line treatment for PMDD. Both continuous and daily ratings of social isolation and work inefficien- intermittent (only in the symptomatic luteal phase) cy showed significantly greater improvement with dosing regimens are similarly effective and well fluoxetine than with placebo. [49] tolerated by patients with clearly diagnosed PMS/ In summary, measures of functioning of PMDD PMDD. Response to an SSRI is rapid and the dose patients prior to treatment or in community-based required is usually at the low end of the range

9 Antidepressants and Quality of Life in PMDD Yonkers KA, Barnett LK, Carmody T, et al. Serial discontinuation of SSRI treatment for PMDD [abstract]. Biol Psych 1998; indicated for depressive disorders. There is consid- erable functional impairment associated with 43 Suppl. 8: 358 PMDD, being at a level similar to the impairment of depressive disorders. Studies that have systematical- Luso Esp Neurol Psiquiatr Cienc Afines 1997; 25: ly examined functional impairment in PMS/PMDD show that functioning and QOL improve following short-term treatment with an SSRI. Improved func tioning follows symptom improvement, and both occur swiftly with SSRI treatment. 2001; 104: The improvement in functioning and QOL that is experienced with SSRI treatment warrants further efforts to provide effective treatment for this disor- cycles. J Affect Disord 2002; 70 (2): der. The reported impact of PMDD on functional impairment and diminished QOL also indicates a Health 2003; 6: need for increased documentation of the economic and social costs of PMS/PMDD when the disorder 304 remains untreated. Acknowledgements 9. de la Gandara Martin JJ. Premenstrual dysphoric disorder: longterm treatment with fluoxetine and discontinuation. Actas 10. Freeman EW, Sondheimer SJ, Rickels K, et al. A pilot naturalistic follow-up of extended sertraline treatment for severe premenstrual syndrome. J Clin Psychopharm 2004; 24 (3): 11. Angst J, Sellara R, Stolar M, et al. The epidemiology of peri- menstrual psychological symptoms. Acta Psychiatr Scand 12. Cohen LS, Soares CN, Otto MW, et al. Prevalence and predictors of premenstrual dysphoric disorder (PMDD) in old- er premenopausal women: the Harvard study of moods and 13. Steiner M, Macdougall M, Brown E. The premenstrual symp- toms screening tool (PSST) for clinicians. Arch Women Ment 14. Steiner M, Born L. Advances in the diagnosis and treatment of premenstrual dysphoria. CNS Drugs 2000 Apr; 13 (4): Banerjee N, Roy KK, Takkar D. Premenstrual dysphoric disorder: a study from India. Int J Fertil Womens Med 2000 Sep- Oct; 45 (5): Khella AK. Epidemiologic study of premenstrual symptoms. J Egypt Public Health Assoc 1992; 67 (1-2): The author has received previous grant support for antide- 17. McMaster J, Cormie K, Pitts M. Menstrual and premenstrual experiences of women in a developing country. Health Care pressant treatment of PMS/PMDD from Pfizer, Lilly, Wyeth, Women Int 1997 Nov-Dec; 18 (6): Forest and SmithKline Beecham. No outside sources of fundstrual 18. Montero P, Bernis C, Loukid M, et al. Characteristics of mening were used for the preparation of this manuscript. cycles in Moroccan girls: prevalence of dysfunctions and associated behaviours. Ann Hum Biol 1999 May-Jun; 26 (3): References 19. van den Akker OB, Eves FF, Service S, et al. Menstrual cycle symptom reporting in three British ethnic groups. Soc Sci Med 1. ACOG Practice Bulletin. Premenstrual syndrome. Int J Gynecol 1995 May; 40 (10): Obstet 2001 May; 73 (2): Chandra PS, Chaturvedi SK. Cultural variations of premenstrual 2. American Psychiatric Association. Diagnostic and statistical experience. Int J Soc Psychiatry 1989 winter; 35 (4): manual of mental disorders. 4th ed. Washington, DC: Ameri- 21. Chang AM, Holroyd E, Chau JP. Premenstrual syndrome in can Psychiatric Association, 1994: 350 employed Chinese women in Hong Kong. Health Care Women 3. Freeman EW, Rickels K, Schweizer E, et al. Relationships Int 1995 Nov-Dec; 16 (6): between age and symptom severity among women seeking 22. Merikangas KR, Foeldenyi M, Angst J. The Zurich Study. XIX. medical treatment for premenstrual symptoms. Psychol Med Patterns of menstrual disturbances in the community: results of 1995 Mar; 25 (2): the Zurich Cohort Study. Eur Arch Psychiatry Clin Neurosci 4. Wittchen HU, Becker E, Leib R, et al. Prevalence, incidence and 1993; 243 (1): stability of premenstrual dysphoric disorder in the community. 23. Pearlstein TB, Halbreich U, Batzar ED, et al. Psychosocial Psychol Med 2002 Jan; 32 (1): functioning in women with premenstrual dysphoric disorder 5. Freeman EW, Rickels K, Sondheimer SJ. Premenstrual symp- before and after treatment with sertraline or placebo. J Clin toms and dysmenorrhea in relation to emotional distress factors Psychiatry 2000; 61: in adolescents. J Psychosom Obstet Gynecol 1993; 14 (1): 24. Chawla A, Swindle R, Long S. Premenstrual dysphoric disor der: is there an economic burden of illness? Med Care 2002; Sternfeld B, Swindle R, Chawla A, et al. Severity of premenstrual (11): symptoms in a health maintenance organization popula- 25. Morgan M, Rapkin AJ, D Elia L, et al. Cognitive functioning in tion. Obstet Gynecol 2002; 99: premenstrual syndrome. Obstet Gynecol 1996; 88: Roca CA, Schmidt PJ, Rubinow DR. A follow-up study of 26. Resnick A, Perry W, Parry B, et al. Neuropsychological perpremenstrual syndrome. J Clin Psychiatry 1999; 60: formance across the menstrual cycle in women with and with-

10 442 Freeman out premenstrual dysphoric disorder. Psychiatry Res 1998; 77: 44. Steiner M, Steinberg S, Stewart D, et al. Fluoxetine in the treatment of premenstrual dysphoria. N Engl J Med 1995; 332: 27. Robinson RL, Swindle RW. Premenstrual symptom severity: impact on social functioning and treatment-seeking behaviors. 45. Wood SH, Mortola JF, Chan YF, et al. Treatment of premen- J Womens Health 2000; 9 (7): strual syndrome with fluoxetine: a double-blind, placebo-con- 28. Campbell EM, Peterkin D, O Grady K, et al. Premenstrual trolled, crossover study. Obstet Gynecol 1992; 80: symptoms in general practice patients: prevalence and treatsevere 46. Menkes DB, Taghavi E, Mason PA. Fluoxetine treatment of ment. J Reprod Med 1997; 42: premenstrual syndrome. BMJ 1992; 305: Kuczmierczyk AR, Labrum AH, Johnson CC. Perception of 47. Ozeren S, Corakci A, Yucesoy I, et al. Fluoxetine in the treatfamily and work environments in women with premenstrual ment of premenstrual syndrome. Eur J Obstet Gynecol Reprod syndrome. J Psychosom Res 1992; 36: Biol 1997; 73: Borenstein JE, Dean BB, Endicott J, et al. Health and economic 48. Pearlstein TB, Stone AB, Lund SA. Comparison of fluoxetine, impact of the premenstrual syndrome. J Reprod Med 2003; 48: bupropion, and placebo in the treatment of premenstrual dysphoric disorder. J Clin Psychopharmacol 1997; 17: Hallman J, Georgiev N. The premenstrual syndrome and abtreatment 49. Su TP, Schmidt PJ, Danaceau MA, et al. Fluoxetine in the sence from work due to illness. J Psychosom Obstet Gynaecol of premenstrual dysphoria. Neuropsychopharmacol- 1987; 6: ogy 1997; 16: Halbreich U, Borenstein J, Pearlstein T, et al. The prevalence, 50. Cohen LS, Miner C, Brown E, et al. Premenstrual daily fluoxeimpairment, impact, and burden of premenstrual dysphoric tine for premenstrual dysphoric disorder: a placebo-controlled, disorder (PMS/PMDD). Psychoneuroendocrinology 2003; 28: clinical trial using computerized diaries. Obstet Gynecol 2002; : Murray CJL, Lopez AD. The global burden of disease: a comintermittent, luteal phase sertraline treatment of premenstrual 51. Halbreich U, Bergeron R, Yonkers KA, et al. Efficacy of prehensive assessment of mortality and disability from diseasdysphoric disorder. Obstet Gynecol 2002 Dec; 100 (6): es, injuries, and risk factors in 1990 and projected to Global burden of disease and injury series. Boston: The 29 Harvard School of Public Health, on behalf of the World 52. Freeman EW, Rickels K, Sondheimer SJ, et al. Differential Health Organization and the World Bank, 1996 response to antidepressants in women with premenstrual syndrome/premenstrual dysphoric disorder. Arch Gen Psychiatry 34. Hall RCW, Wise MG. The clinical and financial burden of 1999; 56: mood disorders: cost and outcome. Psychosomatics 1995; 36 (2): S Yonkers KA, Halbreich U, Freeman E, et al. Symptomatic improvement of premenstrual dysphoric disorder with ser- 35. Simon GE, Vonkorff M, Barlow W. Health-care costs of primatraline treatment: a randomized controlled trial. JAMA 1997; ry-care patients with recognized depression. Arch Gen Psychi- 278: atry 1995; 52 (10): Young SA, Hurt PH, Benedek DM, et al. Treatment of premen- 36. Johnson J, Weissman MM, Klerman GL. Service utilization and strual dysphoric disorder with sertraline during the luteal social morbidity associated with depressive symptoms in the phase: a randomized, double-blind, placebo-controlled crosscommunity. JAMA 1992; 267: over trial. J Clin Psychiatry 1998; 59: Horwath E, Johnson J, Klerman GL, et al. Depressive symptoms 55. Jermain DM, Preece CK, Sykes RL, et al. Luteal phase seras relative and attributable risk factors for first-onset major traline treatment for premenstrual dysphoric disorder: results depression. Arch Gen Psychiatry 1992; 49: of a double-blind, placebo-controlled, crossover study. Arch 38. Barnard K, Frayne SM, Skinner KM, et al. Health status among Fam Med 1999; 8: women with menstrual symptoms. J Womens Health 2003; Halbreich U, Smoller JW. Intermittent luteal phase sertraline (9): treatment of dysphoric premenstrual syndrome. J Clin Psychia- 39. Rosen LN, Moghadam LZ, Endicott J. Relationship between try 1997; 58: premenstrual symptoms and general well-being. Psychosomat- 57. Eriksson E, Hedberg A, Andersch B, et al. The SRI paroxetine is ics 1990 Winter; 31 (1): superior to the noradrenaline reuptake inhibitor maprotiline in 40. Hartlage SA, Arduino KE, Gehlert S. Premenstrual dysphoric the treatment of premenstrual syndrome: a placebo-controlled disorder and risk for major depressive disorder: a preliminary trial. Neuropsychopharmacology 1995; 12: study. J Clin Psychol 2001; 57 (12): Wikander I, Sundblad C, Andersch B, et al. Citalopram in 41. Rubinow DR, Schmidt PJ, Roca CA. Estrogen-serotonin inter- premenstrual dysphoria: is intermittent treatment during luteal actions: implications for affective regulation. Biol Psychiatry phases more effective than continuous medication throughout 1998; 44: the menstrual cycle? J Clin Psychopharmacol 1998; 18: Dimmock PW, Wyatt KM, Jones PW, et al. Efficacy of selective 59. Freeman EW, Rickels K, Yonkers KA, et al. Venlafaxine in the serotonin-reuptake inhibitors in premenstrual syndrome: a sys- treatment of premenstrual dysphoric disorder. Obstet Gynecol tematic review. Lancet 2000; 256: ; 98: Wyatt KM, Dimmock PW, O Brien PM. Selective serotonin 60. Sundblad C, Modigh K, Andersch B, et al. Clomipramine effecreuptake inhibitors for premenstrual syndrome. Cochrane tively reduces premenstrual irritability and dysphoria: a place- Database Syst Rev 2002; (4): CD bo-controlled trial. Acta Psychiatr Scand 1992; 85: 39-47

11 Antidepressants and Quality of Life in PMDD Sundblad C, Hedberg M, Eriksson E. Clomipramine adminis- 77. Schmidt PJ, Grover GN, Rubinow DR. Alprazolam in the treattered during the luteal phase reduces the symptoms of premen- ment of premenstrual syndrome: a double-blind, placebo-construal syndrome: a placebo controlled trial. Neuropsychophar- trolled trial. Arch Gen Psychiatry 1993 Jun; 50 (6): macology 1993; 9: Thys-Jacobs S, Starkey P, Bernstein D, et al. Calcium carbonate 62. Freeman EW, Rickels K, Sondheimer SJ, et al. Nefazodone in and the premenstrual syndrome: effects on premenstrual and the treatment of premenstrual syndrome: a preliminary study. J menstrual symptoms. Premenstrual Syndrome Study Group. Clin Psychopharmacol 1994; 14: Am J Obstet Gynecol 1998 Aug; 179 (2): Freeman EW, Rickels K, Sondheimer SJ. Fluvoxamine for 79. Pearlstein T, Steiner M. Non-antidepressant treatment of prepremenstrual dysphoric disorder: a pilot study. J Clin Psychia- menstrual syndrome. J Clin Psychiatry 2000; 61 Suppl. 12: 22- try 1996; 57 Suppl. 8: Stevinson C, Ernst E. Complementary/alternative therapies for 64. Graham CA, Sherwin BB. A prospective treatment study of premenstrual syndrome: a systematic review of randomized premenstrual symptoms using a triphasic oral contraceptive. J controlled trials. Am J Obstet Gynecol 2001 Jul; 185 (1): 227- Psychosom Res 1992 Apr; 36 (3): Freeman EW, Kroll R, Rapkin A, et al. Evaluation of a unique 81. Pearlstein T. Selective serotonin reuptake inhibitors for premenoral contraceptive in the treatment of premenstrual dysphoric strual dysphoric disorder. Drugs 2002; 62 (13): disorder. J Womens Health Gend Based Med 2001 Jul-Aug; Altshuler LL, Cohen LS, Moline ML, et al. The Expert Consen- (6): sus Guideline Series: treatment of depression in women. Post- 66. Brown CS, Ling FW, Andersen RN, et al. Efficacy of depot grad Med 2001 Mar; (Spec No): leuprolide in premenstrual syndrome: effect of symptom se- 83. Freeman EW, Sondheimer SJ, Polansky M, et al. Predictors of verity and type in a controlled trial. Obstet Gynecol 1994 Nov; response to sertraline treatment of severe premenstrual syn- 84 (5): dromes. J Clin Psychiatry 2000; 61: Freeman EW, Sondheimer SJ, Rickels K. Gonadotropin-releas- 84. Sundström-Poromaa I, Bixo M, Björn I, et al. Compliance to ing hormone agonist in the treatment of premenstrual symp- antidepressant drug therapy for treatment of premenstrual syntoms with and without ongoing dysphoria: a controlled study. drome. J Psychosom Obstet Gynecol 2000; 21: Psychopharmacol Bull 1997; 33 (2): Miner C, Brown E, McCray S, et al. Weekly luteal-phase dosing 68. Hammarback S, Backstrom T. Induced anovulation as treatment with enteric-coated fluoxetine 90mg in premenstrual dysphoric of premenstrual tension syndrome: a double-blind cross-over disorder: a randomized, double-blind, placebo-controlled study with GnRH-agonist versus placebo. Acta Obstet clinical trial. Clin Ther 2002; 24: Gynecol Scand 1988; 67 (2): Zajecka J, Tracey KA, Mitchell S. Discontinuation symptoms 69. Hussain SY, Massil JH, Matta WH, et al. Buserelin in premenreview. after treatment with serotonin reuptake inhibitors: a literature strual syndrome. Gynecol Endocrinol 1992 Mar; 6 (1): J Clin Psychiatry 1997; 58 (7): Wyatt K, Dimmock P, Jones P, et al. Efficacy of progesterone 87. Pearlstein T, Gillespie JA. When should premenstrual dosing in and progestogens in management of premenstrual syndrome: PMDD end? [poster]. 155th Annual APA Meeting; 2002 May systematic review. BMJ 2001 Oct 6; 323 (7316): , Philadelphia 88. Clayton AH, Pradko JF, Croft HA, et al. Prevalence of sexual 71. Berger CP, Presser B. Alprazolam in the treatment of two dysfunction among newer antidepressants. J Clin Psychiatry subsamples of patients with late luteal phase dysphoric disor- 2002; 63: der: a double-blind, placebo-controlled crossover study. Obstet Gynecol 1994 Sep; 84 (3): Steiner M, Brown E, Trzepacz P, et al. Fluoxetine improves functional work capacity in women with premenstrual 72. Freeman EW, Rickels K, Sondheimer SJ, et al. A double-blind dysphoric disorder. Arch Women Ment Health 2003; 6: 71-7 trial of oral progesterone, alprazolam, and placebo in treatment 90. Weissman MM, Bothwell S. Assessment of social adjustment of severe premenstrual syndrome. JAMA 1995 Jul 5; 274 (1): by patient self-report. Arch Gen Psychiatry 1976; 33: Endicott J, Nee J, Harrison W, et al. Quality of life enjoyment 73. Harrison WM, Endicott J, Nee J. Treatment of premenstrual and satisfaction questionnaire: a new measure. Psychopharmadysphoria with alprazolam: a controlled study. Arch Gen Psycol Bull 1993; 29: chiatry 1990 Mar; 47 (3): Endicott J, Harrison W. Daily rating of severity of problems 74. Rickels K, Freeman E, Sondheimer S. Buspirone in treatment of form. New York (NY): Department of Research Assessment premenstrual syndrome [letter]. Lancet 1989 Apr 8; 1 (8641): and Training, New York State Psychiatric Institute, Steiner M, Haskett RF, Carroll BJ. Premenstrual tension syn- 75. Smith S, Rinehart JS, Ruddock VE, et al. Treatment of premen- drome: the development of research diagnostic criteria and strual syndrome with alprazolam: results of a double-blind, new rating scales. Acta Psychiatr Scand 1980; 62: placebo-controlled, randomized crossover clinical trial. Obstet 94. Leon AC, Olfson M, Portera L, et al. Assessing psychiatric Gynecol 1987 Jul; 70 (1): impairment in primary care with the Sheehan Disability Scale. 76. Dennerstein L, Morse C, Burrows G, et al. Alprazolam in the Int J Psychiatry Med 1997; 27: treatment of premenstrual syndrome. In: Dennerstein L, Fraser 95. McGahuey CA, Gelenberg AJ, Laukes CA, et al. The Arizona I, editors. Hormones and behavior. New York (NY): Elsevier Sexual Experience Scale (ASEX): reliability and validity. J Science Publishing, 1986: Sex Marital Ther 2000; 26 (1): 25-40

12 444 Freeman 96. Yonkers K, Gillespie JA. Quality of life impairment and response in PMDD [poster]. 155th Annual APA Meeting; 2002 Correspondence and offprints: Dr Ellen W. Freeman, De- May 18-23, Philadelphia partment of Obstetrics/Gynecology, 3701 Market Street, 97. Kraemer GR, Kraemer RR. Premenstrual syndrome: diagnosis Mudd Suite #820, Philadelphia, PA , USA. and treatment experiences. J Womens Health 1998; 7: freemane@mail.med.upenn.edu